A PHASE 3, RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING PREGNANCY
Phase: PHASE3
Conditions: Respiratory Tract Infection
Sponsor: Pfizer

C3671008
PFIZER CONFIDENTIAL
16.1.1. FINAL PROTOCOL AND PROTOCOL AMENDMENTS
16.1.1.1. C3671008 Protocol Amendment 7 Clean Copy, 08Aug2022
16.1.1.2. C3671008 Protocol Amendment 6 Clean Copy, 01Jun2022
16.1.1.3. C3671008 Protocol Amendment 5 Clean Copy, 12Jan2022
16.1.1.4. C3671008 Protocol Amendment 4 Clean Copy, 22Mar2021
16.1.1.5. C3671008 Protocol Amendment 3 Clean Copy, 26Aug2020
16.1.1.6. C3671008 Protocol Amendment 2 Regional Specific, Clean Copy, 26Jun2020
16.1.1.7. C3671008 Protocol Amendment 1 Clean Copy, 24Mar2020
16.1.1.8. C3671008 Clinical Protocol 05Dec2019
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PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine)
Protocol C3671008
Protocol Amendment 7, 08 August 2022
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLINDED,
PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND 
SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F 
SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING 
PREGNANCY
Investigational Product Number:
PF-06928316
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine
United States (US) Investigational New 
Drug (IND) Number:
017931
European Clinical Trials Database 
(EudraCT) Number:
2019-002943-85
ClinicalTrials.gov Identification (ID):
NCT04424316
Protocol Number:
C3671008
Phase:
3
Short Title: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants 
Born to Women Vaccinated During Pregnancy.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine)
Protocol C3671008
Protocol Amendment 7, 08 August 2022
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 2
Document History
Document
Version Date
Protocol amendment 7
08 August 2022
Protocol amendment 6
01 June 2022
Protocol amendment 5
12 January 2022
Protocol amendment 4
22 March 2021
Protocol amendment 3
26 August 2020
Protocol amendment 2
26 June 2020
Protocol amendment 1
24 March 2020
Original protocol
05 December 2019
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs) and any global protocol administrative change letter(s) (PACL[s]).
Protocol Amendment Summary of Changes Table
Amendment: 7 (08 August 2022)
Section # and 
Name
Description of 
Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 2.2: 
Background
Reinstated the
statistical analysis 
plan (SAP) from 
protocol amendment 5 
and revised the alpha 
analysis for the study.
This change was made 
to address the Food and 
Drug Administration 
(FDA) Center for 
Biologics Evaluation 
and Research’s 
(CBER’s) comments 
pertaining to protocol 
amendment 6
Substantial 
Section 4.1: 
Overall Design
Reinstated the SAP 
from protocol 
amendment 5 and 
revised the alpha 
analysis for the study.
This change was made 
to address CBER’s 
comments pertaining to
protocol amendment 6
Substantial
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PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine)
Protocol C3671008
Protocol Amendment 7, 08 August 2022
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 3
Section # and 
Name
Description of 
Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 4.1.2: 
Approximate 
Number of 
Participants
Reinstated the SAP 
from protocol 
amendment 5 and 
revised the alpha 
analysis for the study.
This change was made 
to address CBER’s
comments pertaining to
protocol amendment 6
Substantial
Section 9.2: 
Sample Size 
Determination
Reinstated the SAP 
from protocol 
amendment 5 and 
revised the alpha 
analysis for the study.
This change was made 
to address CBER’s
comments pertaining to
protocol amendment 6
Substantial
Section 9.4.1: 
Efficacy 
Analysis
Reinstated the SAP 
from protocol 
amendment 5 and
revised the alpha 
analysis for the study.
This change was made 
to address CBER’s
comments pertaining to
protocol amendment 6
Substantial
Section 9.5: 
Interim 
Analyses 
Reinstated the SAP 
from protocol 
amendment 5 and 
revised the alpha 
analysis for the study.
This change was made 
to address CBER’s
comments pertaining to
protocol amendment 6
Substantial
Section 8.11.1: 
Infant 
Participants: 
Visit 1 – Birth 
(Hospital, Birth 
to 7 Days After 
Birth)
Added clarification 
regarding the 
collection of infant 
participant data, 
specifically the full 
date of birth on the 
study.
This is to provide 
clarification and ensure 
consistency with the 
study protocol 
requirements at
investigational sites.
Nonsubstantial
Section 9.4.3.1:
Immunogenicity 
Analysis
Deleted text 
pertaining to the 
maternal IgG subclass 
level immunogenicity 
analysis.
This is to align with the 
exploratory
immunogenicity 
analysis planned for the 
study. 
Nonsubstantial
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PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine)
Protocol C3671008
Protocol Amendment 7, 08 August 2022
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 4
Section # and 
Name
Description of 
Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 10.12
Appendix 12: 
Country-
Specific 
Appendix –
Applicable to 
New Zealand 
Only
Added a country-
specific appendix for 
New Zealand that 
addresses the 
collection and 
overseas transfer of 
identifiable 
participant data, 
specifically the date 
of birth, to the 
Sponsor based on 
national regulatory 
laws and 
recommendations.
This change was made 
at the request of the
New Zealand Health 
and Disabilities Ethics 
Committee (HDEC) to 
reflect local regulatory 
requirements as per 
PACL #12. 
Nonsubstantial 
Document 
History, 
Protocol 
Amendment 
Summary of 
Changes Table,
and 
Section 10.13: 
Protocol 
Document 
History 
Incorporated Pfizer 
protocol template text 
revisions to the 
document history and 
the summary of 
changes table. The 
previous amendment 
history has been 
moved to Section 
10.13.
Not applicable (N/A)
Nonsubstantial 
Protocol Title 
Page
Incorporated Pfizer 
protocol template 
revision to the 
protocol title page and 
added the study’s 
Clinicaltrials.gov ID.
N/A
Nonsubstantial 
Throughout
Minor editorial 
revisions as 
appropriate.
N/A
Nonsubstantial
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PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine)
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Protocol Amendment 7, 08 August 2022
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................12
1. PROTOCOL SUMMARY...................................................................................................13
1.1. Synopsis ..................................................................................................................13
1.2. Schematic for Study Participants ............................................................................22
1.2.1. Study Design – Maternal Participants ........................................................22
1.2.2. Study Design – Infant Participants .............................................................23
1.2.3. Schedule of Activities for Maternal Participants........................................24
1.2.3.1. Schedule of Activities for Maternal Participants: RTI 
Surveillance for Medically Attended Respiratory Tract Illness 
Visits (Vaccination Until the End-of-Study Visit) ............................27
1.2.4. Schedule of Activities for Infant Participants.............................................28
1.2.4.1. Schedule of Activities for Infant Participants: Respiratory 
Tract Illness Study Visits During the Study......................................30
2. INTRODUCTION ...............................................................................................................33
2.1. Study Rationale .......................................................................................................34
2.2. Background .............................................................................................................34
2.3. Benefit/Risk Assessment.........................................................................................35
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................37
3.1. Infant Participants ...................................................................................................37
3.2. Maternal Participants...............................................................................................43
3.3. Protocol-Defined Efficacy Endpoints .....................................................................44
4. STUDY DESIGN.................................................................................................................44
4.1. Overall Design.........................................................................................................44
4.1.1. Approximate Duration of Participation for Each Participant .....................46
4.1.2. Approximate Number of Participants.........................................................46
4.2. Scientific Rationale for Study Design.....................................................................46
4.3. Justification for Dose ..............................................................................................46
4.4. End of Study Definition ..........................................................................................48
5. STUDY POPULATION......................................................................................................48
5.1. Inclusion Criteria.....................................................................................................49
5.1.1. Inclusion Criteria – Maternal Participants..................................................49
5.1.2. Inclusion Criteria – Infant Participants.......................................................51
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5.2. Exclusion Criteria....................................................................................................51
5.2.1. Exclusion Criteria – Maternal Participants.................................................51
5.2.2. Exclusion Criteria – Infant Participants......................................................53
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants ................54
5.3. Lifestyle Considerations..........................................................................................54
5.4. Screen Failures ........................................................................................................54
6. STUDY INTERVENTION..................................................................................................54
6.1. Study Intervention(s) Administered........................................................................55
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........55
6.1.2. Placebo........................................................................................................55
6.1.3. Administration............................................................................................55
6.1.4. Medical Devices .........................................................................................56
6.2. Preparation/Handling/Storage/Accountability ........................................................56
6.2.1. Preparation and Dispensing........................................................................57
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................57
6.3.1. Blinding of Study Site Personnel................................................................57
6.3.2. Blinding of the Sponsor..............................................................................58
6.3.3. Allocation to Investigational Product .........................................................58
6.3.4. Breaking the Blind......................................................................................58
6.4. Study Intervention Compliance...............................................................................59
6.5. Concomitant Therapy..............................................................................................59
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................59
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................59
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................60
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................60
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................60
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications –
Infant Participants............................................................................................60
6.6. Dose Modification...................................................................................................61
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6.7. Intervention After the End of the Study..................................................................61
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................61
7.1. Discontinuation of Study Intervention ....................................................................61
7.2. Participant Discontinuation/Withdrawal From the Study.......................................61
7.3. Withdrawal of Consent............................................................................................62
7.4. Lost to Follow-up....................................................................................................62
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................63
8.1. Efficacy Assessments..............................................................................................63
8.1.1. Efficacy Assessments – Infant Participants................................................63
8.1.1.1. Midturbinate Nasal Swab Collection and Testing 
Requirements for Endpoint Confirmation – Infant Participants........64
8.1.1.2. Events for Adjudication and Submission Guidance –
Infant Participants..............................................................................65
8.1.2. Exploratory Efficacy Assessments – Maternal Participants.......................66
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal 
and Infant Participants .....................................................................................66
8.1.4. Immunogenicity Assessments ....................................................................66
8.1.4.1. Total Volume of Blood Collected – Maternal Participants.......66
8.1.4.2. Total Volume of Blood Collected – Infant Participants............66
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant 
Participants ........................................................................................67
8.1.4.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development – Maternal and Infant 
Participants ........................................................................................67
8.1.4.5. Respiratory Pathogens – Infant Participants .............................68
8.1.4.6. Biological Samples – Maternal and Infant Participants............68
8.2. Safety Assessments .................................................................................................68
8.2.1. Participant Electronic Diary – Maternal Participants .................................68
8.2.1.1. Local Reactions – Maternal Participants...................................70
8.2.1.2. Systemic Events – Maternal Participants..................................71
8.2.1.3. Temperature – Maternal Participants ........................................73
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant 
Participants.......................................................................................................74
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8.3. Adverse Events and Serious Adverse Events..........................................................74
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......74
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................76
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................77
8.3.2. Method of Detecting AEs and SAEs ..........................................................77
8.3.3. Follow-up of AEs and SAEs.......................................................................77
8.3.4. Regulatory Reporting Requirements for SAEs...........................................78
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Investigational Product ..........................................................................78
8.3.5.1. Exposure During Breastfeeding ................................................78
8.3.5.2. Occupational Exposure .............................................................79
8.3.6. Cardiovascular and Death Events...............................................................80
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................80
8.3.8. Adverse Events of Special Interest.............................................................80
8.3.8.1. Lack of Efficacy........................................................................81
8.3.9. Medical Device Deficiencies......................................................................81
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........81
8.3.9.2. Follow-up of Medical Device Deficiencies...............................81
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................81
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................82
8.3.10. Medication Errors.....................................................................................82
8.4. Treatment of Overdose............................................................................................83
8.5. Pharmacokinetics ....................................................................................................83
8.6. Pharmacodynamics..................................................................................................83
8.7. Genetics...................................................................................................................83
8.7.1. Specified Genetics ......................................................................................83
8.8. Biomarkers ..............................................................................................................84
8.9. Health Economics ...................................................................................................84
8.10. Procedures – Maternal Participants.......................................................................84
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8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to 
Vaccination to Day 1 – Visit 1) .......................................................................84
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After 
Vaccination).....................................................................................................88
8.10.3. Delivery (Maternity Unit).........................................................................89
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 
210 Days After Delivery).................................................................................90
8.10.5. Unscheduled Reactogenicity Visits..........................................................91
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria –
Maternal Participants .......................................................................................93
8.11. Procedures – Infant Participants............................................................................94
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After 
Birth)................................................................................................................94
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After 
Birth)................................................................................................................95
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 
Days After Birth) .............................................................................................97
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 
Days After Birth) .............................................................................................98
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days 
After Birth; Infant Participants Born During the First Year of the Study 
Only) ................................................................................................................99
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 
742 Days After Birth; Infant Participants Born During the First Year of 
the Study).......................................................................................................100
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 
6 Months After Delivery)...............................................................................101
8.11.7.1. Study Visits Following a Medically Attended RTI –
Hospital, Home, or Clinic Visit.......................................................101
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit 
Criteria ...........................................................................................................103
8.12. Nasal Swab Collection ........................................................................................104
8.13. Communication and Use of Technology.............................................................105
9. STATISTICAL CONSIDERATIONS ..............................................................................106
9.1. Estimands and Statistical Hypotheses...................................................................106
9.1.1. Estimands – Infant Participants ................................................................106
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9.1.1.1. Efficacy ...................................................................................106
9.1.1.2. Immunogenicity ......................................................................107
9.1.1.3. Safety.......................................................................................107
9.1.2. Estimands – Maternal Participants ...........................................................107
9.1.2.1. Immunogenicity ......................................................................107
9.1.2.2. Safety.......................................................................................108
9.2. Sample Size Determination...................................................................................108
9.3. Populations for Analysis .......................................................................................109
9.4. Statistical Analyses ...............................................................................................110
9.4.1. Efficacy Analyses .....................................................................................110
9.4.2. Safety Analyses ........................................................................................113
9.4.3. Other Analyses..........................................................................................114
9.4.3.1. Immunogenicity Analyses.......................................................114
9.4.3.2. Healthcare Utilization Analyses..............................................115
9.5. Interim Analyses ...................................................................................................116
9.5.1. Data Monitoring Committee.....................................................................117
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................118
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............118
10.1.1. Regulatory and Ethical Considerations ..................................................118
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................119
10.1.2. Financial Disclosure ...............................................................................119
10.1.3. Informed Consent Process ......................................................................119
10.1.4. Data Protection .......................................................................................121
10.1.5. Dissemination of Clinical Study Data ....................................................121
10.1.6. Data Quality Assurance ..........................................................................122
10.1.7. Source Documents..................................................................................123
10.1.8. Study and Site Closure............................................................................124
10.1.9. Publication Policy...................................................................................124
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................125
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................125
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10.2.1. Definition of AE .....................................................................................126
10.2.2. Newly Diagnosed Chronic Medical Conditions.....................................127
10.2.3. Definition of SAE...................................................................................127
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs.....................129
10.2.5. Reporting of SAEs..................................................................................132
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......132
10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting............................................134
10.4.1. Definition of AE and ADE .....................................................................134
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device 
Effect, and Unanticipated Serious Adverse Device Effect............................135
10.4.3. Definition of Device Deficiency.............................................................135
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................136
10.4.5. Reporting of SAEs..................................................................................138
10.4.6. Reporting of SADEs...............................................................................138
10.5. Appendix 5: Background Factors........................................................................139
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria 
Checklist for MA-RTI Visit – Infant Participants...................................................139
10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only...............142
10.7.1. Informed Consent for the Maternal Participants <20 Years Old............142
10.7.2. Temperature Measurement and Definition of Fever ..............................143
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants.........143
10.7.3.1. Enrollment of Maternal Participants in the Sentinel 
Cohort..............................................................................................143
10.7.3.2. Conclusion of the Sentinel Cohort ........................................143
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or 
Telephone; 14 to 16 Days After Vaccination).................................144
10.7.3.4. Schedule of Activities for Maternal Participants Enrolled 
in the Sentinel Cohort in Japan........................................................144
10.7.4. Exclusion Criterion 12 Clarification.......................................................147
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and 
Unanticipated SAE Caused by Medical Device ............................................147
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix –
Applicable to the Philippines, Gambia, and South Africa Only..............................148
10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to 
South Korea and Taiwan Only ................................................................................149
10.10. Appendix 10: Country-Specific Appendix – Applicable to South Korea 
Only.........................................................................................................................150
10.11. Appendix 11: Country-Specific Appendix – Applicable to the Philippines 
Only.........................................................................................................................151
10.12. Appendix 12: Country-Specific Appendix – Applicable to New Zealand 
Only.........................................................................................................................152
10.13. Appendix 13: Protocol Document History........................................................153
10.14. Appendix 14: Abbreviations .............................................................................173
11. REFERENCES ................................................................................................................176
LIST OF TABLES
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants ...............................................................................................37
Table 2.
Endpoint Events and Definitions in Maternal Participants.......................43
Table 3.
Guideline for Infant Blood Draw if Cord Blood Sample Was Not 
Obtained....................................................................................................67
Table 4.
Grading Scale for Local Reactions...........................................................71
Table 5.
Grading Scale for Systemic Events ..........................................................72
Table 6.
Ranges for Fever.......................................................................................74
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals 
at an Interim Analysis.............................................................................117
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1. PROTOCOL SUMMARY
1.1. Synopsis
Indication
Pfizer’s respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSVpreF) 
is a prophylactic vaccine that is being investigated for the prevention of medically attended
RSV-associated lower respiratory tract illness (LRTI) in infants by active immunization of 
pregnant women.
Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given the global burden of disease, maternal immunization offers an attractive 
strategy for infant disease prevention.  Both preclinical studies in animals and interim data 
from a Phase 1/2 study in healthy nonpregnant adults have demonstrated acceptable 
tolerability and safety of RSVpreF.  A robust immune response has also been observed in 
participants from the aforementioned trial. RSVpreF is currently under assessment in healthy 
pregnant women 18 through 49 years of age (Study C3671003: A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blinded Trial to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT04032093).
The safety and tolerability of RSVpreF in pregnant adolescents has yet to be demonstrated. 
Vaccine-elicited immune responses with RSVpreF are expected to be similar in adolescents 
and women based on studies comparing maternal immunization with tetanus, diphtheria, and 
acellular pertussis vaccine (Tdap) and human papillomavirus (HPV) vaccines.  Infants born 
to adolescent mothers are known to be at a higher risk of prematurity, an important risk 
factor for RSV disease. Therefore, pregnant adolescents (18 years of age) are an 
appropriate pediatric population for RSVpreF maternal immunization, providing insight 
toward the efficacy, safety, and tolerability of the vaccine.
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
lower respiratory tract illness (MA-LRTI) in infants.
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Objectives, Estimands, and Endpoints
Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC):

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants 
born to maternal 
participants receiving 
1 dose of investigational 
product, the percentage 
of participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

Adverse events (AEs) from birth to 
1 month of age.

Serious adverse events (SAEs) and 
newly diagnosed chronic medical 
conditions (NDCMCs):
o
from birth through 6 months of
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants 
enrolled during the first year of 
the study).
Secondary Efficacy Objectives
– Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI:

occurring within 210 days after birth.

occurring within 240 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 270 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 270 days meets 
efficacy criteria.
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Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of medically attended 
respiratory tract illness 
(MA-RTI) due to RSV.
RSV-positive MA-RTI:

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs 
from vaccination up to 730 days after 
birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 12 months 
of age.
MA-LRTIs due to RSV occurring 361 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV in infants after 6 months 
of age.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA--LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
To assess the impact of 
RSVpreF on RSV illness based 
on socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
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To assess the effect of RSVpreF 
on healthcare utilization.
Univariate summaries of healthcare 
utilization variables, which may include 
the following: number and type of 
medical visits, length of hospital stay, 
requirement for mechanical ventilation, 
requirement for respiratory diagnostic 
procedures, requirement for intravenous 
(IV) fluids, requirement for prescriptions, 
and antibiotic use.
To describe the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI, 
MA-LRTI, and severe 
MA-LRTI in premature infants 
37 weeks of age.
MA-RTI, MA-LRTI, and severe 
MA-LRTI due to RSV occurring 0 to 
730 days after birth.
Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimand
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery 
study visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum
neutralizing titers and prefusion F 
immunoglobulin G (IgG) titers 
measured:

before vaccination.

at delivery.
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Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis section [Section 9.2]). There is no specific case target for 
the additional primary endpoint of severe MA-LRTI. The total enrollment number of 
maternal participants may vary depending on the incidence rate of the primary endpoint in 
the infant participants, the true underlying VE, and a potential early stop for efficacy or 
futility. In the event that efficacy in the infant population is demonstrated at an interim 
analysis, enrollment of maternal participants may continue in order to obtain safety 
evaluations in an adequate number of maternal and infant participants to support vaccine 
registration with national health authorities.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It was anticipated that approximately 
6900 mother-infant pairs would be needed to accumulate 124 per-protocol cases prior to the 
global coronavirus disease 2019 (COVID-19) pandemic.  With the variable RSV season, the 
sample size may need to be increased and enrollment could go up to 10,000 maternal 
participants based on the number of cases of RSV.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF will be 120 µg 
(60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants. Note: Maternal participants 
will include adolescent females who may be referred to as “minors.” 
Information/assessments for minors may require parental/legal guardian 
awareness/approval per local regulations.
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Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study, all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term respiratory 
tract illness (RTI) surveillance and safety oversight to address safety and the possibility of 
conferred enhanced protection (antibody persistence) during a second RSV season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee.
Planned Duration
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on gestational age (GA) at the time of vaccination and 
when the infant is actually born.
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
Data Monitoring Committee
This study will use an external data monitoring committee (E-DMC) to monitor vaccine 
safety and efficacy and study futility.
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Statistical Methods
The primary hypothesis to be tested is that VE with respect to MA-LRTI due to RSV or 
severe MA-LRTI due to RSV in infants within at least 90 days after birth is more than 20%, 
relative to placebo. The 2 primary endpoints will be tested in parallel using a multiplicity 
adjustment procedure. VE will be estimated using the exact conditional binomial method. 
There will also be hierarchical testing of the primary endpoints to 120 days, 150 days, and 
180 days, conditional on success of the analysis for the shorter intervals. Interim analyses of 
the MA-LRTI-due-to-RSV endpoint with the opportunity to stop the study for efficacy or 
futility may be included. At the end of the trial, the RSV vaccine may be deemed efficacious 
if there are 42 or fewer cases of MA-LRTI due to RSV in the RSV vaccine group out of the 
124 total primary-endpoint cases at 90 days.  This corresponds to an estimated VE = 49%,
with a 97.6% confidence interval (CI) = (21%, 68%). For severe MA-LRTI, assuming a total 
of 50 cases occur, the vaccine may be deemed efficacious if there are 13 or fewer cases in the 
RSV vaccine group.  This corresponds to an estimated VE = 65%, with a 97.6% CI = (26%, 
85%).
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1.2. Schematic for Study Participants
1.2.1. Study Design – Maternal Participants
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1.2.2. Study Design – Infant Participants
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Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
1.2.3. Schedule of Activities for Maternal Participants
Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier
X
Demography
X
Medical history including obstetric historyd
X
Record current/former alcohol, tobacco, marijuana, or any illicit drug 
usage
X
Record vital signs
X
Targeted physical and obstetric examination performed on the same 
day or within 7 days before the vaccination visit
X
Record details of any antenatal and/or postnatal steroid treatment, 
monoclonal antibodies, blood products, or Rho(D) immune globulin
X
X
X
X
Record details of the maternal participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
Review eligibility criteria
X
X
X
Review temporary delay criteria
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Prevaccination blood draw for serologic assessment (~15 mL) on the 
same day or within 7 days before the vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and measuring devicef
X
Obtain and record baseline assessment of prespecified systemic events 
on the day of and prior to vaccination in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic assessment (~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X---------------------------X
Record AEs, as appropriateh
X---------------------------X
Record SAEs, as appropriateh
X
X
X
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of the 
schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; 
ICD = informed consent document; MA-RTI = medically attended respiratory tract illness.
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the LMP and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures and will be 
provided with instructions on their use. Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) a baseline 
assessment of prespecified systemic events on the day of and prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination 
(where Day 1 is the day of vaccination).  Remind maternal participants and their parent(s)/legal guardian (if a minor) that the study staff/field worker may 
contact them to obtain additional information on events entered into the e-diary.  Ask maternal participants or their parent(s)/legal guardian (if a minor) to 
contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 following vaccination, to determine if an 
unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal participant may be referred to the appropriate healthcare facility 
at the discretion of the study staff/field worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 28 days after vaccination.  From the signing of 
the ICD until the maternal participant completes the study, all SAEs will be collected. Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
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1.2.3.1. Schedule of Activities for Maternal Participants: RTI Surveillance for Medically Attended Respiratory Tract Illness
Visits (Vaccination Until the End-of-Study Visit)
Visit Description
Assessments of MA-RTIa
Visit Window
As Soon as Possible After Confirmed MA-RTI
Type of Visit
Telephone
Record details of a confirmed MA-RTI
X
Details of an acute illness visit AND a report of 1 or more of the following RTI
signs and symptoms:

New or increased sore throat

New or increased cough

New or increased nasal congestion

New or increased nasal discharge

New or increased wheezing

New or increased sputum production

New or increased shortness of breath
X
Obtain standard-of-care records, including local NAAT testing results 
(if applicable)b
X
Record nonstudy vaccine information
X
Record AEs and SAEs, as appropriatec
X
Complete the CRF with details
X
Abbreviations: CRF = case report form; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; 
RSV = respiratory syncytial virus; RTI = respiratory tract illness.
a.
Confirmed cases of MA-RTI will be collected from vaccination until the maternal participant completes the study. The assessment of the event would 
involve a telephone call, or a clinic visit if determined by the investigator to be warranted.
b.
Site staff will review and collect data pertaining to the illness and any local NAAT testing results (RSV, influenza, etc), if available.
c.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  MA-RTI events will not be captured as safety 
events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to have resulted in death. Please see 
Section 8.3.1 for reporting requirements and timelines.
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1.2.4. Schedule of Activities for Infant Participants
Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 Days
After Birth
180 to 210 Days
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Assign infant participant identifier
X
Demography
X
Collect background factorsc
X
X
X
X
X
X
Collect birth outcome information including 
infant’s birth data and appearance, pulse, grimace, 
activity, and respiration (Apgar) score
X
Obtain and record infant’s length, head 
circumference, and weight
X
X
X
X
(if clinic visit)
X
(if clinic visit)
Physical examination including vital signs
(temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate) performed within 72 hours 
after birth
X
Obtain and record vital signs, including 
temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate
X
Targeted physical examination (record in the site 
source document)
X
X
X
(if clinic visit)
X
(if clinic visit)
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, 
packed cells)
X
X
X
X
X
X
Review eligibility
X
Cord blood sample (~10 mL) for serologic 
assessmentd
X
Record AEs, as appropriatee
X
Record NDCMCs and SAEs, as appropriatee
X
X
X
X
X
X
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Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 Days
After Birth
180 to 210 Days
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Surveillance reminder contact
Contact with the infant 
participants’ parent(s) or legal 
guardian(s) approximately 
every week until Visit 3
From Visit 3, contact with the infant participant’s parent(s) or legal guardian(s), 
approximately every 28 to 35 days until the end of the study
Assessment of MA-RTIsf,g
Assessment of MA-RTI events 
during the active RSV 
surveillance period as detailed 
in Section 1.2.4.1 of the 
schedule of activities
Assessment of MA-RTI events as detailed in Section 1.2.4.1 of the schedule of 
activities
Abbreviations: MA-RTI = medically attended respiratory tract illness; NDCMC = newly diagnosed chronic medical condition; 
RSV = respiratory syncytial virus; SpO2 = oxygen saturation.
a.
Applicable only for infant participants enrolled during the first year of the study.
b.
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), study visits that cannot be conducted in the clinic or at home, in 
accordance with the protocol requirements, may be conducted via telephone.
c.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV illness.
d.
Cord blood must be obtained on the day of birth. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical cord has 
been clamped and cut. If cord blood is unavailable, a blood sample may be collected from the infant participant preferably within the first 24 hours but up 
to 7 days after birth. The infant’s weight must be used to determine the volume of blood that can be collected.
e.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs, NDCMCs, and SAEs through 28 days after birth.  From 
29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected.  An NDCMC is defined as a disease or medical
condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
f.
A confirmed MA-RTI is defined as an expected study event based on the assessments detailed in the schedule of assessment in Section 1.2.4.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
g.
Reporting MA-RTI events should commence 72 hours after the infant’s delivery.  Respiratory distress events associated with and within 72 hours of birth 
should not be captured as MA-RTI events on the study but should be captured as AEs/SAEs (if applicable).
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1.2.4.1. Schedule of Activities for Infant Participants: Respiratory Tract Illness Study Visits During the Study 
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for All MA-RTIa
Hospital, Home, or Clinic
Follow-Up for
MA-RTI Visit
Telephone
RTI Study Visit for
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Surveillance reminder contact
Contact the infant participants’ parent(s) or 
legal guardian(s) approximately every week 
until Visit 3
From Visit 3, contact the infant participants’ parent(s) or legal 
guardian(s), approximately every 28 -35 days until the end of the 
study
Record confirmed MA-RTI as detailed in Appendix 6, as 
appropriate
X
X
X
Record details of the RTI, including 1 or more of the 
following RTI signs and symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid 
breathing for any duration

Cough

Inability to feed for any duration because of 
respiratory symptoms

Apnea

Any other respiratory symptom of concern
X
X
X
Obtain standard-of-care records and complete CRFc
X
X
X
Record local NAAT testing results, if performed and 
availabled
X
X
X
Perform RTI study visit, record targeted assessment
results (temperature, heart rate, respiratory rate, SpO2 by 
pulse oximetry, chest wall indrawing) and body weight, and 
collect nasal swab (for RT-PCR)e
X
X
Record concomitant medication associated with the 
treatment of the MA-RTI
X
X
X
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for All MA-RTIa
Hospital, Home, or Clinic
Follow-Up for
MA-RTI Visit
Telephone
RTI Study Visit for
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Collect background factors associated with MA-RTIf.
X
X
X
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, packed 
cells)
X
X
X
Record AEs , NDCMCs, and SAEs, as appropriateg
X
X
X
Compile MA-RTI visit source documentation upon 
request by adjudication committee (qualifying 
RSV-positive cases only)
X
X
Abbreviations: CRF = case report form; HCP = healthcare provider; ICU = intensive care unit; IV = intravenous; MA-LRTI = medically attended lower 
respiratory tract illness; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; NDCMC = newly diagnosed 
chronic medical condition; RSV = respiratory syncytial virus; RTI = respiratory tract illness; RT-PCR = reverse transcription–polymerase chain reaction; 
SpO2 = oxygen saturation.
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for All MA-RTIa
Hospital, Home, or Clinic
Follow-Up for
MA-RTI Visit
Telephone
RTI Study Visit for
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
a.
If the infant participant is reported to be experiencing or has had an MA-RTI from birth until Visit 3, the site should arrange a study visit as soon as possible 
and within 72 hours (preferable) or up to 10 days. Ideally, the RTI study visit will be conducted at the investigational study site; however, it is possible that 
the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit where the infant 
participant is residing. Note: Reporting MA-RTI events should commence 72 hours after the infant’s delivery.
b.
If the infant participant is reported to be experiencing or has had an MA-RTI associated with severe LRTI criteria or been hospitalized for an RTI from 
Visit 3 until the end of study participation, the site should arrange a RTI study (SRTI) visit as soon as possible and within 72 hours (preferable) or up to 
10 days of the MA-RTI visit. Ideally, assessment of these potential endpoint events (hospitalization due to RTI or severe MA-LRTI) will be conducted at 
the investigational study site; however, it is possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is 
hospitalized) or the site staff may visit where the infant participant is residing. Note: For nonsevere MA-RTIs, a telephone contact with the infant 
participants’ parent(s) or legal guardian(s) is acceptable to complete the follow-up assessments.
c.
Obtain case records, including details of hospitalization, ICU stays, use of oxygen, IV fluids usage, etc.
d.
The site staff/field worker will review and collect data related to any local NAAT testing results, if performed and available.
e.
The site staff/field worker will collect nasal swabs for confirmed MA- RTIs, including confirmed cases of hospitalizations due to an RTI and severe 
MA-LRTIs. In the event that restrictions prevent taking RTI study swabs because of an outbreak, pandemic situation, or natural disaster, the study nasal 
swab can be collected for processing at Pfizer’s central laboratory by the infant caregiver, during or within 10 days following an MA-RTI visit, or by the 
HCP assessing the infant during the MA-RTI visit (in addition to any samples obtained in the course of routine clinical care) as detailed in Section 8.11.7.1
and Section 8.11.8.
f.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV. This will be collected for 
all MA-RTI events reported.
g.
The investigator and site staff/field worker will ensure the active elicitation and collection of NDCMCs and SAEs through the end-of-study visit for the 
infant participant. From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected. An NDCMC is defined 
as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma). Note: A 
confirmed MA-RTI will not be captured as a safety event, unless the investigator or an appropriate designee deems it to be related to the investigational 
product or to have resulted in death.
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2. INTRODUCTION
Prevention of RSV disease in young infants is a significant unmet medical need globally.  
RSV is the leading cause of bronchiolitis and viral pneumonia in infants and can lead to fatal 
respiratory distress, especially in those with risk factors including premature infants with 
underlying cardiopulmonary disease, or in the absence of effective healthcare systems.1
However, most cases of RSV disease occur in healthy, full-term infants without risk factors.2
Worldwide, RSV kills approximately 118,200 children annually, with about half of those 
deaths occurring in infants under 6 months of age, and the majority of those occurring in 
resource-limited countries.3,4 In the United States (US), RSV is the leading cause of infant 
hospitalization, with more than 60,000 hospitalizations of children 12 months of age and 
younger annually.5,6  There is increasing evidence that the link between severe RSV disease 
in infancy and wheezing later in childhood may be causal.7,8  Like influenza, RSV infection 
follows a seasonal pattern, causing illness primarily in the cooler months of the year in 
temperate regions and during the wet season in tropical countries with seasonal rainfall.9  
Infection is essentially universal by the time children reach 2 years of age.10
Currently, there is neither specific treatment for RSV infection nor a vaccine to protect 
against RSV disease.  Treatment consists primarily of supportive care.  A prophylactic 
humanized monoclonal antibody, palivizumab (Synagis, AstraZeneca), targeting the RSV F 
glycoprotein is available for prevention of severe RSV disease in young infants at increased 
risk.11  Limitations of its use include its high cost12 and requirement of multiple monthly 
injections,13 and so it remains recommended for use only in very premature infants and 
others at increased risk of severe illness.6,14
Nevertheless, the protective effect of Synagis provides definitive proof of principle that 
serum neutralizing antibody directed against the F protein can provide clinically meaningful 
protection against RSV lower respiratory tract disease in young infants.15  Furthermore, it is 
well known that in other disease settings, antibodies transferred from mothers to their fetuses 
across the placenta can reduce infant disease early in life,16,17,18,19,20,21 suggesting that 
maternal immunization is a reasonable approach to RSV disease prevention among young 
infants.
There are 2 antigenic variants of RSV, namely, RSV subgroup A (RSV A) and RSV 
subgroup B (RSV B).  The RSV vaccine being investigated in this study is a bivalent vaccine 
composed of stable RSV prefusion F antigens representing the 2 subgroups to help ensure the 
broadest coverage against RSV illness.
RSVpreF is a prophylactic vaccine being developed to prevent medically attended
RSV-associated LRTI in infants by active immunization of pregnant women.
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2.1. Study Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given a global burden of disease in the millions of cases each year, maternal 
immunization offers an attractive strategy for infant disease prevention.  Both preclinical 
studies in animals and interim data from a Phase 1/2 study in healthy nonpregnant adults 
have demonstrated acceptable tolerability and safety of RSVpreF.  A robust immune 
response has also been observed in the population of the aforementioned trial, at 1 month 
after vaccination. The combined RSV A and B serum neutralization geometric mean titers 
(GMTs) have been shown to be 12 to 20 times higher than those with 100 μg/mL of
palivizumab, the concentration of the monoclonal antibody that is known to provide near to 
complete protection of high-risk infants from severe RSV disease.22,23 RSVpreF is currently 
under assessment in healthy pregnant women 18 through 49 years of age (Study C3671003, 
A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093).
The safety and tolerability of RSVpreF in pregnant adolescents has yet to be demonstrated. 
Vaccine-elicited immune responses with RSVpreF are expected to be similar in adolescents 
and women based on studies comparing maternal immunization with Tdap and HPV 
vaccination.24,25,26  Infants born to adolescent mothers are known to be at a higher risk of 
prematurity, an important risk factor for RSV disease.27,28 Therefore, pregnant adolescents 
(18 years of age) are an appropriate pediatric population for RSVpreF maternal 
immunization, providing insight toward the efficacy, safety, and tolerability of the vaccine.
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
RSV-associated LRTI in infants.
2.2. Background
RSV is an important cause of morbidity and mortality worldwide, with a substantial burden 
of disease borne by young infants.  Rates of severe RSV illness are highest in infants 
6 months of age, with a peak in hospitalization between 1 and 2 months of life, though the
highest case-fatality rates are observed in the neonatal period (<1 month).2 Infants born 
prematurely and those with underlying cardiac or pulmonary disease are at further increased 
risk of severe clinical disease due to RSV.  A 2017 retrospective case analysis that examined 
RSV mortality data from 23 countries demonstrates the global nature of the seriousness of 
RSV disease, with significant morbidity and mortality occurring in both lower- and 
middle-income countries (LMICs) and high-income countries.3,4
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No specific treatments for RSV exist, and available prophylactic measures (ie, RSV 
monoclonal antibody) are limited to use in only those infants at highest risk; additionally, in 
LMICs, use of available RSV prophylaxis is cost-prohibitive.  While active immunization 
against RSV in infants might be an option, multiple efforts, extending over half a century, to 
develop a safe and effective RSV vaccine to protect infants from disease have yielded little 
success.  The early peak of disease presents a further obstacle to an active vaccination 
strategy for infants.  Given these challenges, maternal immunization to protect infants early 
in life offers an attractive strategy for infant disease prevention.
The present RSV vaccine efforts were initiated in early 2014 based on a new scientific 
discovery (determination of the RSV prefusion F crystal structure)29 and a changing 
regulatory and policy environment that today supports the development of vaccines for 
maternal immunization to protect very young infants.  The trimeric RSV F surface 
glycoprotein in a prefusion conformation is now known to be the primary target of 
neutralizing antibodies and is the basis for the engineered antigens in Pfizer’s vaccine 
candidate.  Applying structure-guided vaccine design, Pfizer has developed a stabilized RSV 
prefusion F vaccine candidate.  The core hypothesis underlying Pfizer’s RSV vaccine 
development effort for prevention of infant disease is that vaccine antigens based on RSV 
prefusion F, when administered to pregnant women in the second or third trimester of 
pregnancy, will elicit sufficiently high neutralizing antibody titers that, when the antibodies
are actively transferred transplacentally to the fetus, will protect infants against RSV disease. 
The aim is for neutralizing antibody levels to be at sufficient levels such that infants will be 
protected from birth and possibly through their first RSV season.
2.3. Benefit/Risk Assessment
RSVpreF is being evaluated in ongoing clinical studies.  Pfizer’s maternal immunization 
approach circumvents the risk of vaccine-mediated disease enhancement that was observed 
in the 1960s following direct immunization of RSV-naive infants with a formalin-inactivated 
RSV vaccine (FI-RSV).30  FI-RSV elicited a predominantly nonneutralizing antibody 
response and a Th2-biased cell-mediated response, both of which are considered potential 
contributing factors to disease enhancement.31  During preclinical studies, in a standard 
cotton rat infectious RSV challenge model, FI-RSV showed pathological signs of causing 
disease enhancement, and the current Pfizer vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease enhancement has not been reported to occur in 
RSV-experienced individuals after immunization with any RSV vaccine candidate.  Because 
pregnant women are universally RSV-experienced, they are not considered at risk for a 
disease-enhancing immune response to the vaccine that could exacerbate infection in 
themselves.  Enhanced disease has not been observed in infants born to mothers who
received prior investigational RSV vaccines; therefore, enhanced disease in infants is very
unlikely.  A previous study of maternal immunization with a Wyeth (later merged with 
Pfizer) investigational RSV vaccine (PFP-2) showed an acceptable safety profile, even 
though this candidate contained a postfusion RSV F antigen that elicited a relatively weak 
RSV-neutralizing antibody response and a higher nonneutralizing RSV-binding antibody 
response in pregnant women.32  A recently completed Phase 3 maternal RSV trial (Novavax) 
with an RSV vaccine containing F not stabilized in the prefusion form, given to over 
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4600 healthy pregnant volunteers, showed a similar safety profile in the RSV vaccine and 
placebo groups.33
Vaccination with the RSV prefusion F antigens elicit a higher ratio of neutralizing to 
nonneutralizing antibodies, more closely matching the profile in naturally exposed 
individuals.  The safety profile of RSVpreF observed to date is similar to that of prior RSV F 
subunit vaccines tested in RSV-experienced adults.
There are limited data on the global burden of maternal RSV infection, likely in part because 
of infrequent diagnostic testing. However, in one multisite study, RSV-associated disease in 
pregnancy was shown to result in prolonged hospitalization and an increased likelihood of 
preterm birth in women who tested RSV-positive.34 It is possible that vaccination may 
benefit the pregnant women who receive it. RTI in mothers who receive RSVpreF will be 
explored in this study.  The benefit of maternal vaccination is accrued to the infant by means 
of transplacental antibody transfer.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the investigator’s brochure (IB), which is the 
single reference safety document (SRSD) for this study.
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Infant Participants
The study objectives and endpoints for infant participants employ the event definitions in 
Table 1.
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study Endpoints/Assessments
Study Definitions
Medically attended visit
Infant participant has been taken to or seen by a healthcare provider 
(eg, outpatient or inpatient visit, emergency room, urgent care, or home 
visit)
MA-RTI visit for infant 
participant
A medically attended visit AND 1 or more of the following RTI signs and 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any 
duration

Cough

Inability to feed for any duration because of respiratory symptoms

Apnea

Any other respiratory symptom of concern
RSV-positive testa

RSV RT-PCR–positive test result by Pfizer central laboratory
OR

RSV-positive test result by certified laboratory with NAAT for RSV
MA-RTI due to RSVb

An MA-RTI visit
AND

RSV-positive test result as described in Section 8.1.1.1
MA-LRTI due to any cause

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age], 
≥50 bpm for ≥2 months to <12 months of age, or ≥40 bpm for 
≥12 months to 24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age] or 
≥50 bpm for ≥2 to <12 months of age, or ≥40 bpm for ≥12 months to 
24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
AND

RSV-positive test result as described in Section 8.1.1.1
Hospitalized RTI due to RSVb
An RTI due to RSV that results in hospitalization
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Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study Endpoints/Assessments
Study Definitions
Severe MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥70 bpm for <2 months of age [<60 days of age], 
≥60 bpm for ≥2 months to <12 months of age, or ≥50 bpm for 
≥12 months to 24 months of age) OR

SpO2 <93% OR

High-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive) OR

ICU admission for >4 hours OR

Failure to respond/unconscious
AND

RSV-positive test result as described in Section 8.1.1.1
Protocol-defined primary 
endpoint

Any MA-LRTI or severe MA-LRTI due to RSV as determined by an 
EAC
Abbreviations: bpm = breaths per minute; EAC = endpoint adjudication committee; ICU = intensive care unit; 
MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically attended respiratory tract 
illness; NAAT = nucleic acid amplification technology; RR = respiratory rate; 
RSV = respiratory syncytial virus; RTI = respiratory tract illness; SpO2 = oxygen saturation.
a.
RSV-positive testing is defined as a positive RSV test (see Section 8.1.1.1) conducted on a sample 
obtained during the medically attended visit or within 10 days (where Day 1 is the day of the MA-RTI 
visit) as detailed in Section 8.11.7.
b.
The EAC will determine if the endpoint criteria have been met upon review of the site source 
documentation from the MA-RTI visit and RTI study visits, including all available RSV test results.
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Study Objectives – Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due 
to RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the EAC:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants born 
to maternal participants 
receiving 1 dose of 
investigational product, 
the percentage of 
participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

AEs from birth to 1 month of age.

SAEs and NDCMCs:
o
from birth through 6 months of 
age (first RSV season for all infant 
participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants enrolled 
during the first year of the study).
Secondary Efficacy Objectives –
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), defined 
as the relative risk reduction of 
the endpoint in the RSV 
vaccine group compared to the 
placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI:

occurring within 210 days after birth.

occurring within 240 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 270 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 270 days meets 
efficacy criteria.
Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI due to 
RSV.
RSV-positive MA-RTI:

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs from 
vaccination up to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 12 months of 
age.
MA-LRTIs due to RSV occurring 361 to 
730 days after birth.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI due 
to RSV in infants after 6 months 
of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV in infants after 6 months of 
age.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI in 
the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
To assess the impact of RSVpreF 
on RSV illness based on 
socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
To assess the effect of RSVpreF 
on healthcare utilization.
Univariate summaries of healthcare 
utilization variables, which may include the 
following: number and type of medical 
visits, length of hospital stay, requirement 
for mechanical ventilation, requirement for 
respiratory diagnostic procedures, 
requirement for IV fluids, requirement for 
prescriptions, and antibiotic use.
To describe the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI, MA-LRTI, 
and severe MA-LRTI in 
premature infants <37 weeks of 
age.
MA-RTI, MA-LRTI, and severe MA-LRTI
due to RSV occurring 0 to 730 days after 
birth.
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3.2. Maternal Participants
The study objectives and endpoints for maternal participants employ the event definitions in 
Table 2.
Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
Maternal medically attended visit
The maternal participant reports a visit with a healthcare 
provider (eg, outpatient or inpatient visit, emergency room, 
urgent care, or home visit)
MA-RTI visit maternal participant
A medically attended visit AND 1 or more of the following 
RTI signs and symptoms:

New or increased sore throat

New or increased cough

New or increased nasal congestion

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production

New or increased shortness of breath
Abbreviations: MA-RTI = medically attended respiratory tract illness; RTI = respiratory tract illness.
Study Objectives – Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimands
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery study 
visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum neutralizing 
titers and prefusion F IgG titers 
measured:

before vaccination.

at delivery.
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3.3. Protocol-Defined Efficacy Endpoints
All infant participants experiencing an MA-RTI will have an RTI study visit as detailed in
Section 8.1.  This protocol will use an independent EAC to determine whether certain 
investigator-reported events meet the definition of disease-related efficacy endpoints, using 
predefined endpoint criteria as summarized in Table 1. Members of this EAC will be blinded 
to the vaccine assignment to allow for unbiased assessments.
Recognizing that RSV disease is a dynamic illness, sites will be instructed to submit all 
available source documentation for adjudication from the MA-RTI visit and to record data 
from the worst day of illness in the electronic case report form (eCRF).  The EAC will 
determine if the endpoint criteria have been met upon review of the site source
documentation from the MA-RTI visit, including data collected at the RTI study visit, and all 
available RSV testing.  Further information about the EAC will be detailed in the 
adjudication charter, including specific descriptions of the scope of its responsibilities and 
the process and definitions to review and assess study endpoints.
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition and 
constitute a study endpoint will not be recorded as AEs.  For those AEs that are handled as 
disease-related efficacy endpoints, a data monitoring committee (DMC) will conduct 
unblinded reviews on a regular basis throughout the trial (see Data Monitoring Committee,
Section 9.5.1).
Nonendpoint events (eg, an event that is determined not to be an MA-RTI) must be evaluated 
for safety reporting as per the protocol requirements.  Any AE that is adjudicated by the EAC
to not meet any endpoint criteria will be reported back to the investigator site of incidence;
the investigator at the site must evaluate the event for safety as described in Appendix 2 of 
this protocol.  If the event is classified as serious, the investigator’s SAE awareness date in 
this instance is identified as the date on which the investigator site receives the nonendpoint 
SAE back from the EAC.  Handling these SAEs in this manner will allow Pfizer to meet its 
sponsor reporting obligations to regulatory authorities upon receipt of such SAEs.
Any events that remain unadjudicated at the annual safety report cutoff date will not be 
included in the safety tables of the report.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
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This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of 
MA-LRTI due to RSV at 90 days (meeting the case definition in the per-protocol infant 
population described in the statistical analysis (Section 9.2). There is no specific case target 
for the additional primary endpoint of severe MA-LRTI. The total enrollment number of 
maternal participants may vary depending on the incidence rate of the primary endpoint in 
the infant participants, true underlying VE, and a potential early stop for efficacy or futility. 
In the event that efficacy in the infant population is demonstrated at an interim analysis, 
enrollment of maternal participants may continue in order to obtain safety evaluations in an 
adequate number of maternal and infant participants to support vaccine registration with 
national health authorities. Enrollment will be monitored to ensure even distribution of 
vaccination across gestational age between 24 0/7 and 36 0/7 weeks.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It was anticipated that approximately 
6900 mother-infant pairs would be needed to accumulate the 124 per-protocol cases prior to 
the global COVID-19 pandemic.  With the variable RSV season, the sample size may need to 
be increased and enrollment could go up to 10,000 maternal participants based on the number 
of cases of RSV.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF for this study will be 
120 µg (60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.
Note: Maternal participants will include adolescent females who may be referred to as 
“minors.”  Information/assessments for minors may require parental/legal guardian 
awareness/approval per local regulations.
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term RTI 
surveillance and safety oversight to address safety and the possibility of conferred enhanced 
protection (antibody persistence) during a second RSV season.
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All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. In addition, this study will use an 
E-DMC to monitor vaccine safety and efficacy and study futility.
4.1.1. Approximate Duration of Participation for Each Participant
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on GA at the time of vaccination and when the infant is 
actually born.
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
4.1.2. Approximate Number of Participants
Healthy pregnant women will be randomly assigned to a study intervention. It was 
anticipated that approximately 6900 mother-infant pairs would be needed to accumulate 
124 per-protocol cases as defined in Section 9.2 of the protocol prior to the global COVID-19 
pandemic.  With the variable RSV season, the sample size may need to be increased and 
enrollment could go up to 10,000 maternal participants based on the number of cases of 
RSV.  Enrollment will be monitored to ensure that participants will be recruited from both 
the northern and southern hemispheres. Enrollment may vary depending on the incidence in 
the placebo group, the true underlying VE, the dropout rate, and a potential early stop for VE
or futility.
4.2. Scientific Rationale for Study Design
Refer to Section 2.1.
4.3. Justification for Dose
The final dose and formulation of RSVpreF selected for use in this study is based on the 
safety and immunogenicity data from the ongoing C3671003 maternal immunization study
(A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093) and the first-in-human (FIH) study C3671001.
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The FIH study was designed to describe the safety, tolerability, and immunogenicity of 
6 RSVpreF candidates with bivalent formulations (RSV A and B) at 3 escalating dose levels 
of 60 µg (30 µg A and 30 µg B), 120 µg (60 µg A and 60 µg B), and 240 µg (120 µg A and 
120 µg B) of the RSV prefusion F antigen, with or without Al(OH)3, when administered 
alone or concomitantly with seasonal inactivated influenza vaccine.  The study utilizes a 
sentinel cohort (N=168; Phase 1) and an expanded cohort (N=1014; Phase 2).  Nonpregnant 
female and male study participants of 2 age groups, 18 through 49 years of age and 
50 through 85 years of age, were enrolled into both cohorts.  The age groups are being run in 
parallel.
An interim analysis of participants 18 through 49 years of age, including safety and 
tolerability (n=533) and immunogenicity (n=513) data up to 1 month after vaccination in the 
expanded cohort and additional immunogenicity data up to 3 months after vaccination in the 
sentinel cohort, has shown the RSVpreF candidate to be immunogenic and well tolerated.
Local reactions and systemic events were noted to be predominantly mild or moderate across 
all doses and formulations, which is consistent with the current safety profile. The safety 
results from this planned interim analysis of healthy male and nonpregnant female 
participants 18 through 49 years of age are consistent with those from the sentinel-cohort 
analysis and indicate that RSVpreF has an acceptable safety profile and is well tolerated.
The immunogenicity results showed that RSVpreF elicited neutralizing titer geometric mean 
fold rises (GMFRs) of 10 to 20, 1 month after vaccination, depending on the formulation. 
Similarly, across all dose levels, with and without Al(OH)3, RSVpreF elicited high 
1-month-postvaccination RSV A and RSV B neutralizing GMTs. Overall, RSVpreF elicited 
anti–prefusion F immunoglobulin G1 (IgG1) responses that paralleled the elicited 
RSV-neutralizing responses. The ratio of RSV 50% neutralizing antibody titer GMFRs to 
prefusion RSV F binding IgG1 titer GMFRs (calculated with combined data for subgroups A 
and B) for the sentinel and expanded 18 through 49 years of age cohorts combined ranged 
from 0.62 to 0.76. The IgG1 and neutralization responses were similar in antigen-level dose
response, in equivalence of RSV A titer GMFRs to RSV B titer GMFRs, and in a lack of 
effect of Al(OH)3.
Safety data for 403 mother/infant pairs, from maternal participants through 1 month after
maternal vaccination and for their infants from birth through the first month of life, in 
Study C3671003 provide further evidence of the safety of RSVpreF in maternal vaccine 
recipients, and initial evidence of the safety of maternal vaccination with RSVpreF for the 
infant. In maternal participants, solicited symptoms were generally mild to moderate in 
intensity and of short duration. Unsolicited AEs were consistent with anticipated events in 
this participant population and did not indicate any differences between RSVpreF and control 
recipients. No differences in pregnancy (eg, reports of preterm delivery or obstetric 
complications) and birth outcomes (eg, reports of respiratory distress at delivery or presence 
of congenital anomalies) were observed between RSVpreF and control recipients. No 
differences in the number or types of AEs reported were observed between infants born to 
mothers receiving RSVpreF and those receiving placebo in the first month of life.
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The high ratio of RSV-neutralizing antibody titer GMFRs to prefusion F–binding titer 
GMFRs elicited by Pfizer’s RSVpreF candidate indicates that most of the elicited antibody 
can neutralize the virus. It is assumed that this reflects the ability of the antibodies to prevent 
RSV disease in immunized participants and, in the case of maternal immunization, prevent 
disease in their infants.
The primary mechanism for protection of infants by the RSV maternal vaccine is 
neutralization of the virus by transplacentally transferred antibody, which is increased by 
immunization.  Maternal antibody decays exponentially in infants.  Therefore, it is 
anticipated that higher titers of transferred neutralizing antibodies will provide greater levels 
and durations of infant protection.  Results from the C3671001 FIH trial were used to 
determine the doses and formulations that are currently under investigation in the Phase 2b 
maternal immunization study: 120 µg or 240 µg of RSVpreF with or without Al(OH)3. 
These doses are expected to provide the greatest potential level of transplacental antibody 
transfer to infants and, therefore, the greatest potential benefit.  The dose and formulation of 
RSVpreF for the Phase 3 study was determined by the evaluation of the 1-month safety, 
tolerability, and immunogenicity results from the C3671003 maternal Phase 2b trial,
including infant RSV-neutralizing titers at birth.
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last visit.
The end of the study is defined as the date of the last visit of the last infant participant in the 
study. The study may also be terminated earlier for efficacy or futility as described in
Section 9.5.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1. Inclusion Criteria
5.1.1. Inclusion Criteria – Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply 
(refer to the investigator site file [ISF] for further eligibility details regarding region-specific 
timing of vaccination with respect to RSV seasonality and maternal gestational age at 
vaccination):
Note: In countries/locales where study procedures used to determine eligibility criteria 
(eg, ultrasound examination, human immunodeficiency virus [HIV] testing, syphilis testing) 
are not performed as part of routine prenatal care, they must be performed as part of this 
clinical trial and reviewed by the investigator or qualified designee within 28 days prior to 
randomization.  Maternal participants must provide informed consent prior to 
performing any procedures, including those that are being done exclusively to meet 
study eligibility criteria.
Note: Country-specific modifications associated with the study eligibility criteria are 
documented in Appendix 7, Appendix 8, and Appendix 9.
Age and Sex:
1. Healthy women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation 
on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are 
at no known increased risk for complications.
Note: GA must be based upon 1 of the following composite criteria based on timing and 
availability of data on the last menstrual period (LMP) and an ultrasound examination 
performed in the first or second trimester.35  The earliest ultrasound data available during 
the current pregnancy should be used. In countries where the routine practice is for the 
GA determination to be based upon the first trimester ultrasound examination alone, 
without the LMP, this routine practice will be accepted.
a.
First-trimester data available (data obtained at ≤13 6/7 weeks):
The date of the first day of the reported LMP may be used to establish the GA if corroborated 
by a first-trimester ultrasound examination.
If there is a discrepancy of 5 days between the LMP-determined GA and an ultrasound
result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA should be determined 
using the first-trimester ultrasound result.
If there is a discrepancy of 7 days between the LMP-determined GA and an ultrasound
result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, then the GA should be 
determined using the first-trimester ultrasound result.
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b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):
The date of the first day of the reported LMP may be used to establish the GA if corroborated 
by a second-trimester ultrasound result.
If there is a discrepancy of 7 days between the LMP-determined GA and the ultrasound
result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, then the GA should be 
determined using the second-trimester ultrasound result.
If there is a discrepancy of 10 days between the LMP-determined GA and the ultrasound
result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, then the GA should be 
determined using the second-trimester ultrasound result.
If there is a discrepancy of 14 days between the LMP-determined GA and the ultrasound
result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, then the GA should be 
determined using the second-trimester ultrasound result.
Type of Participant and Disease Characteristics:
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Receiving prenatal standard of care based on country requirements.
4. Had a fetal anomaly ultrasound examination performed at ≥18 weeks of pregnancy with 
no significant fetal abnormalities observed.
5. Determined by medical history, physical examination, and clinical judgment to be 
appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) 
surface antigen test during this pregnancy and prior to randomization (Visit 1).
7. Intention to deliver at a hospital or birthing facility where study procedures can be 
obtained.
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol OR
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If the maternal participant is illiterate, a thumbprinted informed consent must be 
obtained, which must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process confirming that the maternal participant 
has been informed of all pertinent aspects of the study.
5.1.2. Inclusion Criteria – Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a 
thumbprinted informed consent must have been obtained, which must have been signed 
and dated by an impartial witness who was present throughout the entire informed 
consent process confirming that the maternal participant/parent(s)/legal guardian(s) has 
been informed of all pertinent aspects of the study for herself (maternal participant) and 
her fetus/infant prior to taking part in the study.
Note: Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements.
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
5.2. Exclusion Criteria
5.2.1. Exclusion Criteria – Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not 
available, the BMI at the time of the first obstetric visit during the current pregnancy may 
be used.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any related 
vaccine.
4. Current pregnancy resulting from in vitro fertilization.  Participants known to have used 
clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are 
permitted.
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5. Current pregnancy complications or abnormalities at the time of consent that will 
increase the risk associated with the participation in and completion of the study, 
including but not limited to the following:

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.

Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated 
hypothyroidism.  This also includes disorders of glucose intolerance (eg, diabetes 
mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if 
uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the 
investigator’s judgment, that will increase the risk associated with the participation in and 
completion of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks’ gestation.

Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or significant congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the maternal 
or infant participant’s participation in, and completion of, the study or could preclude the 
evaluation of the maternal participant’s response (includes positive serologic testing for 
regional endemic conditions assessed during routine maternal care, as per local standards 
of care and obstetric recommendations).
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment.
9. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
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Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to 
consent and/or during study participation.
11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of 
systemic corticosteroids for >14 days within 28 days prior to study enrollment. 
Permitted treatments include the receipt of severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) monoclonal antibodies, prednisone doses of <20 mg/day 
for ≤14 days and, inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) 
corticosteroids.
12. Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an 
exclusion criterion for the study when elicited in participant screening, though it may be 
considered illicit in some locales.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before 
investigational product administration, or planned receipt through delivery, with 
1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt 
during study participation. Note: Licensed COVID-19 vaccines or COVID-19 vaccines 
authorized for temporary, or emergency use will not be prohibited during the course of 
this study.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
5.2.2. Exclusion Criteria – Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
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5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and if no other exclusion criteria are met.  
The prevaccination blood draw and vaccination should take place on the same day. In the 
event that this is not possible, the prevaccination blood draw is also permissible within 7 days 
before the vaccination visit.

Current febrile illness (body temperature ≥38°C [≥100.4°F]) or other acute illness within 
48 hours before investigational product administration.

Diagnosed malaria within the last 7 days prior to investigational product administration.

Receipt of any inactivated vaccine (including licensed COVID-19 vaccines or COVID-19 
vaccines authorized for temporary or emergency use) within 14 days or any live vaccine 
within 28 days before investigational product administration.

If systemic corticosteroids (equivalent of ≥20 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical 
study but are not subsequently randomly assigned to investigational product. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs.
Maternal participants who do not meet the criteria for participation in this study (screen 
failure) may be rescreened.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
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6.1. Study Intervention(s) Administered
For this study, the investigational product(s) are RSVpreF and placebo (lyophile match).
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.  
The RSV vaccine will be 120 µg of the RSV prefusion F antigen.  The vaccine is supplied as 
a lyophilized white cake in a 2-mL glass vial, with a 13-mm lyophilization stopper, 
aluminum overseal, and flip-off cap. The vaccine will be reconstituted by a diluent 
consisting of sterile water in a prefilled syringe (PFS). The lyophilized vaccine contains 
excipients that, after reconstitution, will yield a solution as detailed in the IB.
The fill volume of the vaccine vial and diluent PFS are designed such that the intended 
vaccine dose is delivered by injecting the entire contents of the syringe.
6.1.2. Placebo
Placebo will be a lyophile match to the vaccine, which will consist of excipients matched to 
those used in the RSVpreF vaccine formulation, minus the active ingredients.
The physical appearance of the reconstituted RSVpreF and placebo will be matched, and the 
study will be conducted in a double-blinded manner.
The fill volume of the placebo vial and diluent PFS is designed such that the intended 
placebo dose is delivered by injecting the entire contents of the syringe.
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
6.1.3. Administration
Maternal participants will receive 1 dose of investigational product at the vaccination visit 
(Day 1) in accordance with the study’s SoA.  The investigational product will be 
administered intramuscularly by injecting the entire contents of the syringe into the deltoid 
muscle, preferably of the nondominant arm, unless medically contraindicated, in which case 
the injection may be administered in the dominant arm. Investigational product
administration will be performed by appropriately designated study staff at the investigator 
site.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
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Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance.
Investigational product administration details will be recorded on the case report form (CRF).
6.1.4. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluent for the 
investigational product (RSV vaccine or placebo). The investigational product supplies are 
provided in a kit that contains the investigational product (RSV vaccine or placebo 
lyophilized powder in a vial), a prefilled syringe containing sterile water, and a vial adapter.
Instructions for medical device use are provided in the investigational product manual 
(IP manual).
Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the study personnel throughout the study.
Please refer to Section 8.3.9 for details.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention, as applicable for 
temperature-monitored shipments.
2. Only maternal participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking days must indicate the minimum and maximum 
temperature since previously documented for all site storage locations upon return to 
business.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  All study interventions will be 
accounted for using an investigational product accountability form/record.
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual.
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5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
6. Study interventions should be stored in their original containers and in accordance with 
the labels.
7. See the IP manual for storage conditions of the study intervention once reconstituted.
8. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use of 
the study intervention after the temperature excursion. Use of the study intervention prior 
to Pfizer approval will be considered a protocol deviation. Specific details regarding the 
definition of an excursion and information the site should report for each excursion will 
be provided to the site in the IP manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
6.2.1. Preparation and Dispensing
Refer to the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
Investigational product and placebo will be prepared by qualified site personnel according to 
the IP manual.  The investigational product will be administered only to maternal participants 
who are blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Blinding of Study Site Personnel
This study is a double-blinded study, as the physical appearance of RSVpreF and placebo 
will be matched. The maternal participant, her parent(s)/legal guardian (if a minor), 
investigator, study coordinator, and all site staff will be blinded.
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Please refer to the IP manual for further details.
6.3.2. Blinding of the Sponsor
The sponsor study team members will be blinded throughout the study to the vaccine 
assignments of all participants enrolled in the study.
Laboratory personnel performing the serology and virology assays will remain blinded to 
vaccine assigned/received throughout the study.
6.3.3. Allocation to Investigational Product
Allocation (randomization) of maternal participants to vaccine groups will proceed through 
the use of an interactive response technology (IRT) system (interactive Web-based response 
[IWR]).  The site personnel (study coordinator or specified designee) will be required to 
enter or select information including but not limited to the user’s identification (ID) and 
password, the protocol number, and the maternal participant number.  The site personnel will 
then be provided with a vaccine assignment, randomization number, and dispensable unit 
(DU) or container number as investigational product is being supplied via the IRT system.  
The IRT system will provide a confirmation report containing the maternal participant 
number, randomization number, and DU or container number assigned. The confirmation 
report must be stored in the site’s files.
Note: Maternal participants will be randomized to a vaccine group as described above.  The 
infants of the maternal participants will be manually assigned an infant participant number at 
birth.
Investigational product will be dispensed and administered at study Visit 1 summarized in 
the SoA.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Maternal participants will be assigned to receive investigational product according to the 
randomization scheme.  Investigators will remain blinded to the investigational product 
assigned to each maternal participant throughout the course of the study.
6.3.4. Breaking the Blind
The study will be maternal participant and investigator blinded.
At the initiation of the study, the investigator will be instructed on the method for breaking
the blind for an individual participant.  The method will be an electronic process.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the participant.  The 
investigators should make every attempt to contact a member of the sponsor’s study team 
prior to breaking the blind.  When the blinding code is broken, the reason must be fully
documented and entered on the CRF.
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The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal Participants

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study. Note: COVID-19 vaccines authorized for temporary, or emergency use will not be 
prohibited during the course of this study.

Receipt of blood/plasma products or Ig, from 60 days before investigational product 
administration, or planned receipt through delivery, with 1 exception, Rho(D) immune 
globulin (eg, RhoGAM), which can be given at any time.

Immunosuppressive therapy is prohibited during the course of the study.

Nonstudy vaccines may not be given concomitantly with the investigational product or 
within 7 days after investigational product administration (Day 1 to Day 7), except if 
medically necessary (eg, during an outbreak or pandemic situation).

Note: Licensed vaccines containing pertussis (including Tdap) may not be 
coadministered with the investigational product or given within 14 days after 
investigational product administration (Day 1 to Day 14), except if medically necessary 
(eg, during an outbreak- or pandemic-related situation).
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal Participants

Licensed vaccines (including influenza vaccine, tetanus toxoid, tetanus diphtheria 
vaccines, licensed COVID-19 vaccines, and COVID-19 vaccines authorized for 
temporary or emergency use) may be given during the study starting 7 days after
investigational product administration (Day 8), with the exception of licensed vaccines 
containing pertussis (including Tdap), which may be given starting 14 days after 
investigational product administration (Day 15) as detailed in Section 6.5.1.

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. Short-term systemic corticosteroid (equivalent of <20 mg/day of prednisone)
use for ≤14 days prior to the administration of investigational product is permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during participant participation in the 
study.
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6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following vaccinations and treatments for maternal participants would require reporting 
in the CRF during the study:

Details of any vaccinations given at any time during the pregnancy through the final 
study visit will be collected and recorded in the CRF.

Details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given to the maternal participant at any time during the 
pregnancy or during the study will be collected and recorded in the CRF.

Any prescribed medications taken to treat medically attended respiratory illnesses from 
enrollment until the final study visit will be recorded in the CRF.
Concomitant medications not meeting the criteria above will be assessed but not documented 
on the CRF.
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant Participants

Investigational vaccines, drugs, nutritional products, or medical devices are prohibited 
during the course of the study.
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant Participants

ONLY routine treatments, routine vaccinations, and routine procedures 
(eg, circumcision) are permitted at any time during the study, in accordance with national 
recommendations, medical standard of care, or accepted practice.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during infant participant participation in the study.

Local anesthetic may be applied to the site of the blood draw, as appropriate.
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications – Infant 
Participants
The following CRF reporting guidelines are applicable to treatments given to infant 
participants during the study:

Details of any Ig (including monoclonal antibodies [eg, Synagis] or immune globulin 
[eg, hepatitis B immune globulin (HBIG)]) or blood products (eg, whole blood, packed 
cells) given to the infant participant will be collected from the time of birth until the final 
study visit and recorded in the CRF.

Any prescribed medication taken to treat medically attended respiratory illnesses from 
the time of birth until the final visit.
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
Details of IV fluids given during an MA-RTI will be collected and recorded in the CRF.
6.6. Dose Modification
Dose modification is not applicable in this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Discontinuation of study intervention is not applicable in this study.
7.2. Participant Discontinuation/Withdrawal From the Study
A maternal participant may withdraw from the study at any time at her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. An infant participant may withdraw from the study at 
any time at the request of his or her parent(s) and/or legal guardian(s) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.
The participants, or, if appropriate, their parent(s) and/or legal guardian(s), should be
questioned regarding their reason for withdrawal. The participant will be permanently
discontinued from the study at that time.
If a maternal participant withdraws from the study, she may request destruction of any 
remaining samples taken and not tested, but data already generated from the samples will 
continue to be available and may be used to protect the integrity of existing analyses. If an 
infant participant is withdrawn from the study, his or her parent(s) and/or legal guardian(s) 
may request destruction of any remaining samples, but data already generated from the 
samples will continue to be available and may be used to protect the integrity of existing 
analyses. The investigator must document any such requests in the site study records and 
notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed, and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
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Participants who withdraw after randomization will not be replaced.
7.3. Withdrawal of Consent
Maternal participants and parent(s)/legal guardian(s) of infant participants born to maternal 
participants who request to withdraw consent from any further study contact or with persons 
previously authorized by the participant to provide this information should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible.  The withdrawal of consent should be explained in detail in the medical records by 
the investigator, as to whether the withdrawal is only from study procedures and/or 
postvaccination study follow-up. If the participant (maternal or infant) only withdraws from 
a study procedure, safety information should be completed until the end of the study, unless 
consent for further contact has been withdrawn.  In the event that vital status (whether the 
participant is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
The regulatory and ethical considerations for this study, including the informed consent 
process, are summarized in Section 10.1.1 and Section 10.1.3.
7.4. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant or parent(s) and/or legal guardian(s) and
reschedule the missed visit as soon as possible and counsel the participant or parent(s) 
and/or legal guardian(s) on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or parent(s) and/or legal guardian(s) wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record.
o
Should the participant or parent(s) and/or legal guardian(s) continue to be 
unreachable, the participant will be considered to have withdrawn from the study.
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
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8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the maternal participant’s routine clinical 
management and obtained before signing of the ICD may be utilized for baseline 
purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA and protocol.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
8.1. Efficacy Assessments
8.1.1. Efficacy Assessments – Infant Participants
MA-RTIs in the infant participant will be identified from 72 hours after the infant’s delivery 
until the end of the infant’s participation in the study.  If the infant participant meets any RTI 
criteria listed below that require a visit by or a visit to an HCP (outpatient or inpatient visit, 
emergency room, urgent care, or scheduled home visit), an RTI study visit by the study staff 
will be required (see Section 8.11.7).
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The RTI criteria are if the infant experiences 1 or more of the following respiratory signs or 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any duration

Cough

Inability to feed for any duration due to respiratory symptoms

Apnea

Any other respiratory symptom of concern
Evaluation of these MA-RTI events will be based on predefined clinical signs and symptoms 
and testing criteria (shown in Table 1) obtained at the medically attended visit with the 
healthcare provider and/or the study visit. These events will be assessed and confirmed to be 
contributing to the study endpoints by an independent EAC as per the protocol.
8.1.1.1. Midturbinate Nasal Swab Collection and Testing Requirements for Endpoint 
Confirmation – Infant Participants
Midturbinate nasal swabs will be collected for RSV analyses from infant participants at each 
RTI study visit during the RSV surveillance period from birth until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). The swabs
will be sent to Pfizer for centralized reverse transcription–polymerase chain reaction 
(RT-PCR) testing.
RSV testing performed locally as part of routine care will be considered valid when analyzed 
under the following conditions:

Nucleic acid amplification technology (NAAT)-based test result positive for RSV was 
obtained using an FDA-cleared assay.
AND

NAAT-based test result was obtained in a laboratory that is currently Clinical Laboratory 
Improvement Amendments (CLIA)-certified or has the equivalent US 
certification/accreditation (eg, College of American Pathologists [CAP]) or the equivalent 
ex-US certification as outlined in the adjudication charter.
Note: Rapid antigen-based test results will not be considered for endpoint assessment.
Study samples should be collected as close to the medical visit as possible and preferably 
within 72 hours of the MA-RTI visit. Study samples positive for RSV by RT-PCR as 
defined above will count toward the endpoint definition when collected for up to 10 days 
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after the MA-RTI, where Day 1 is the day of the MA-RTI visit. These results will be used 
for MA-RTI endpoint definition and confirmation as detailed in Table 1.
8.1.1.2. Events for Adjudication and Submission Guidance – Infant Participants
To maintain scientific integrity, this protocol will use an EAC for the adjudication of all 
efficacy endpoints as summarized below.  The EAC will remain blinded to the maternal 
participants’ vaccine assignments, and the EAC’s assessment of these events will represent 
the final confirmed endpoint classification of the event.
The efficacy-related events for adjudication include all MA-RTI events. The study 
definitions for endpoint events and the MA-RTI adjudication criteria for the EAC, including 
roles and responsibilities, are specified in the endpoint adjudication committee charter 
(EACC).
The identification of an MA-RTI will be made by the investigational site and communicated 
to Pfizer or its designee. However, these MA-RTI events may also be identified by Pfizer or 
its designee during the review of clinical data listings or by site monitors during routine 
monitoring of the infant participants’ study records. Pfizer or its designee will notify the 
investigational site of any events identified during this process.
The EAC is responsible for adjudicating whether MA-RTI events fulfill the protocol-defined 
clinical criteria as a primary endpoint, whether the event was due to RSV based on 
confirmatory testing, and the severity of the illness (eg, MA-RTI, MA-LRTI, or severe 
MA-LRTI).  The EAC will adjudicate all RSV-positive MA-RTI cases through the active 
follow-up period including all cases occurring up to 180 days after birth. The EAC will 
adjudicate severe manifestations of RSV: all RSV-associated cases of hospitalization and 
severe MA-LRTI. All deaths during the study are to be reported to Pfizer Safety upon 
awareness.
The Pfizer study team or designee will provide a listing of specific documents needed to 
support endpoint adjudication by the EAC. These documents will be detailed in the EACC
and the ISF.  Obtaining and submitting the documentation, including results of local testing 
for RSV, will be the responsibility of the investigational site. Documentation will vary based 
on the potential endpoint requiring adjudication and may include (but not be limited to) 
emergency room visit records, hospital discharge summaries, clinic and/or progress notes, 
diagnostic tests, pathology reports, autopsy reports, and death certificate information, as 
applicable.
Pfizer may request that additional cases of interest be reported to the committee in addition to 
those listed above, including cases in which RSV testing is indeterminant or otherwise 
unclear. Cases that are determined to be RSV positive using non–NAAT-based clinical 
testing can be adjudicated, explored, and summarized descriptively.
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8.1.2. Exploratory Efficacy Assessments – Maternal Participants
An MA-RTI will be identified from vaccination until the end of the study and will contribute 
to an exploratory endpoint for maternal participants.  The definition and assessment criteria 
as described in Section 8.10.6 include a visit by or to a healthcare provider (outpatient or 
inpatient visit, emergency room, urgent care, or home visit) for any symptoms in the RTI 
criteria as detailed in Table 2.
The maternal participant or her parent(s)/legal guardian (if a minor) should contact the study 
staff immediately but no later than the next scheduled visit to report RTI signs and symptoms 
for which she sought medical attention. The procedures as detailed in Section 1.2.3.1 and 
Section 8.10.6 will be required to capture the event in the CRF.
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal and Infant 
Participants
Infant MA-RTI events that are consistent with the clinical and endpoint definitions for infant 
participants should not be recorded as AEs. These data will be captured as efficacy 
assessment data only, as these are expected endpoints.
For maternal participants, MA-RTI events that are consistent with the clinical and endpoint 
definition will be captured as detailed in Section 8.1.2 and will not be recorded as AEs.
Any event that the investigator has judged to have a causal relationship with the 
investigational product or to have resulted in death MUST be reported to Pfizer Safety as 
described in Appendix 2, even if that event is a component of an endpoint.
8.1.4. Immunogenicity Assessments
8.1.4.1. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be approximately 30 mL (~15 mL/visit).
8.1.4.2. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical 
Consideration for Clinical Trials Performed in Children.36
All infants will have a cord blood sample collected at birth. The cord blood is collected from 
the umbilical cord vein attached to the placenta after the umbilical cord has been clamped 
and cut. Blood should be collected as soon as feasible after birth to minimize coagulation 
and maximize volume. The total volume of cord blood to be collected for antibody 
assessment in this study will be 10 mL.
If cord blood is unavailable, a blood sample may be collected from the infant participant up 
to 7 days after birth but preferably within 24 hours after birth.  The infant’s weight must 
be used to determine the volume of blood that can be collected (see Table 3).
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A blood sample will be collected from the infant participant only if a cord sample is not
obtained. In the event that a sample is collected, the volume of blood will vary depending on 
the infant’s weight.
The maximum volume of blood collected from the infant in the absence of cord blood will be 
no more than 5 mL.
Table 3.
Guideline for Infant Blood Draw if Cord Blood Sample Was Not Obtained
Body Weight (in kg)
Approximate Volume of Blood (in mL)
To Be Collected
1.3
No blood draw
1.3 to ≤2.4
1.0
>2.4 to ≤3.7
2.0
>3.7 to ≤4.9
3.0
>4.9 to ≤6.2
4.0
>6.2
5.0
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant Participants
Maternal sera (prevaccination/time of delivery) and infant cord blood collected will be 
assayed for RSV A and RSV B serum neutralizing titers and anti-RSV prefusion F IgG 
levels. Maternal sera collected may be tested for Ig levels against nonvaccine RSV antigens
to assess natural RSV exposure.
RSV A and RSV B serum neutralizing titers will be determined and reported as the 
neutralizing titer. IgG levels will be determined against both RSV A and RSV B prefusion F 
antigens in a direct-binding Luminex immunoassay (dLIA) and reported as an 
anti–prefusion F IgG level.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development – Maternal and Infant Participants
Samples remaining after completion of the planned assays from blood draws or infant 
respiratory nasal swab specimens taken throughout the study may be used for additional 
vaccine and infectious disease related research. Samples may also be used for assay 
development, standardization, qualification, and validation.  This work is critical in the 
development, qualification, and validation of serological assays and is required by regulatory 
authorities for their use in the licensure of a vaccine.
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8.1.4.5. Respiratory Pathogens – Infant Participants
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI
visit during the RSV surveillance period from birth until Visit 3, and for all hospitalizations 
due to an RTI and severe cases of MA-LRTI during the RTI surveillance period from 
Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1).
Samples will be analyzed for RSV A, RSV B, and other respiratory pathogens by polymerase 
chain reaction (PCR)-based assays at a central laboratory. Additional exploratory analyses 
may also be performed.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.6. Biological Samples – Maternal and Infant Participants
Samples will be used only for scientific research.  Each sample will be labeled with a code so 
that the laboratory personnel testing the samples will not know the maternal or infant
participant’s identity.  Samples that remain after performing assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.  If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No sequencing of the maternal or infant participant’s DNA will be performed.
The maternal participant may request that her (or her infant’s) samples, if still identifiable, be 
destroyed at any time; however, any data already collected from those samples will still be 
used for this research.  The biological samples may be shared with other researchers as long 
as confidentiality is maintained, and no testing of the maternal and infant participant’s DNA 
is performed.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
Safety parameters will be assessed as described in the SoA and below for both maternal and 
infant participants.
8.2.1. Participant Electronic Diary – Maternal Participants
All maternal participants vaccinated in the study will be observed for at least 30 minutes after 
investigational product administration for any acute reactions. For all maternal participants, 
prespecified local reactions and systemic events will be collected for 7 days after vaccination.
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Maternal participants will be required to use an electronic diary (e-diary), installed on a 
provisioned device or as an application on a personal device, and will be asked to monitor 
and record local reactions, systemic events, and temperature each evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  Prior 
to vaccination, a baseline assessment of prespecified systemic events will be recorded in the 
e-diary.
The e-diary allows recording of these assessments only within a fixed time window each day, 
thus providing the accurate representation of the maternal participant’s experience at that 
time.
If the maternal participant is illiterate, a study staff/field worker may visit the maternal 
participant in her home or contact her via phone daily after vaccination to assess and record 
local reactions, systemic events, and temperature each day (beginning in the morning) for 
6 days following vaccination (Day 2 through Day 7). Maternal participants or her 
parent(s)/legal guardian (if a minor) may call the site and report additional local reactions and 
systemic events at any time during the Day 1 to Day 7 reporting period.  The study staff/field 
worker will be required to record these data on a provisioned device or an application on a 
personal device, thus providing the accurate representation of the maternal participant’s 
experience at that time.  For events persisting at Day 7 and use of antipyretic medication 
continuing at Day 7, the field worker will continue to visit the participant and record 
information until resolution.
Data on local reactions, systemic events, and temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via an internet-based 
portal.  At intervals agreed to by the vendor and Pfizer, these data will be transferred 
electronically to Pfizer for analysis and reporting.  These data do not need to be recorded by 
the investigator in the CRF, except the following conditions:

If a maternal participant withdraws because of prompted events recorded in the e-diary, 
the event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF.
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate maternal participant compliance and as part of the 
ongoing safety review. These prospectively collected occurrences of local reactions and 
systemic events are graded as described in Section 8.2.1.1 and Section 8.2.1.2.
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8.2.1.1. Local Reactions – Maternal Participants
Following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), the 
maternal participants or her parent(s)/legal guardian (if a minor)/study staff member/field 
worker will be asked to assess redness, swelling, and pain at the injection site and to record 
the symptoms in the e-diary or appropriate device, in the evening or daily based on local 
practice.
Redness and swelling will be measured by the maternal participant/study staff/field worker 
and recorded in measuring device units (range: 1 to 20 and 21+) and then categorized during 
analysis as mild, moderate, or severe based on the grading scale in Table 4. Measuring 
device units can be converted to centimeters according to the following scale: 1 measuring 
device unit = 0.5 cm.
A maternal participant with severe redness, swelling, or pain at the injection site will be 
prompted to contact the investigator to perform an unscheduled visit to assess the reaction or 
will be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate.  In the event that the maternal participant
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor).
Only an investigator or a qualified designee is able to classify a maternal participant’s local 
reaction as Grade 4, after clinical evaluation of the maternal participant or documentation 
from another medically qualified source (eg, emergency room or hospital record) or, in the 
case of pain at the injection site only, contact with the maternal participant.  If a maternal 
participant experiences a Grade 4 local reaction, the investigator must immediately notify 
the sponsor.  A Grade 4 reaction will be collected as an AE on the CRF.  The event will be 
graded using the AE intensity grading scale (Section 10.2.4).
The site staff/field worker will educate the maternal participant and her parent(s)/legal 
guardian (if a minor) regarding signs and symptoms that would prompt site contact.
If a local reaction persists beyond the end of the e-diary period, the maternal participant or 
her parent(s)/legal guardian (if a minor) will be requested to report that information and/or 
any new AEs that develop to the investigator, or the study staff/field worker will continue to 
call or visit the maternal participant to assess and record the information until resolution, as 
per local practice. The investigator will enter this additional information in the maternal 
participant’s source notes and CRF.
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Table 4.
Grading Scale for Local Reactions
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis
Pain (at the 
injection site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a maternal participant’s local reaction as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
contact with the maternal participant or her parent(s)/legal guardian (if a minor).  Grade 4 local reactions 
will be collected on the AE case report form and assessed by the investigator using the AE intensity 
grading scale as detailed in Section 10.2.4.
8.2.1.2. Systemic Events – Maternal Participants
Prior to vaccination on Day 1, a baseline assessment of fatigue, headache, vomiting, 
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e-diary. Following 
vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), maternal 
participants or their parent(s)/legal guardian (if a minor) will be asked to assess fatigue, 
headache, vomiting, nausea, diarrhea, muscle pain, and joint pain and to record the symptoms 
in the e-diary in the evening or, based on local practice in certain countries/locales, a study 
staff member/field worker will call or visit maternal participants daily after vaccination to 
assess the presence of systemic events each day (beginning in the morning) for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  The 
study staff member/field worker will record the symptoms in the e-diary daily. The 
symptoms will be assessed by the maternal participant according to the grading scale in 
Table 5.  Maternal participants and their parent(s)/legal guardian (if a minor) will also be 
instructed to contact site staff if they visit the emergency room or are hospitalized for severe 
fatigue, headache, vomiting, nausea, diarrhea, muscle pain, or joint pain within 7 days after 
vaccination. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor). The study staff/field worker may also contact the 
maternal participant or her parent(s)/legal guardian (if a minor) to obtain additional 
information on events entered into the e-diary.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic 
event as Grade 4, after clinical evaluation of the maternal participant or documentation from 
another medically qualified source (eg, emergency room or hospital record) or contact with 
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the maternal participant.  If a maternal participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.  Grade 4 reactions will be collected as an 
AE on the CRF.  The event will be graded using the AE intensity grading scale 
(Section 10.2.4).
Further, if a systemic event persists beyond the end of the e-diary period, the maternal 
participant or her parent(s)/legal guardian (if a minor) will be requested to report that 
information and/or any new AEs that develop to the investigator, or the study staff/field 
worker will continue to call or visit the maternal participant to assess and record the 
information until resolution, as per local practice. The investigator will enter this additional 
information in the maternal participant’s source notes and CRF.
Table 5.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness in 
diaries)
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Headache
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Vomiting
1 to 2 times in 24 hours
>2 times
in 24 hours
Requires 
intravenous 
hydration
Emergency room 
visit
or hospitalization 
for severe vomiting
Nausea
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe nausea
Diarrhea
2 to 3 loose stools
in 24 hours
4 to 5 loose stools
in 24 hours
6 or more loose 
stools
in 24 hours
Emergency room 
visit
or hospitalization 
for severe diarrhea
Muscle pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe muscle pain
Joint pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe joint pain
a.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic event as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the maternal participant or her 
parent(s)/legal guardian (if a minor).  Grade 4 systemic reactions will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
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8.2.1.3. Temperature – Maternal Participants
A digital thermometer will be given to the maternal participant with instructions on how to 
measure oral temperature at home in degrees Celsius.  Temperature will be collected in the 
evening for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination) and at any time during the 7 days following vaccination that fever is suspected. 
Similarly, based on local practice in certain countries/locales, the study staff/field worker will 
call or visit maternal participants daily for 6 days after vaccination (Day 2 through Day 7, 
where Day 1 is the day of vaccination) to collect the temperature.
Fever is defined as an oral temperature of ≥38.0°C (≥100.4°F). The highest temperature for 
each day will be recorded in the e-diary, where possible. In certain countries/locales, if a 
temperature of ≥38.0°C (≥100.4°F) is recorded for a maternal participant during the 
collection of diary events after vaccination, the study staff/field worker will perform a rapid 
test for malaria as per local practice.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature less than 38.0°C [100.4°F]) in order to 
collect a stop date in the CRF.
A maternal participant with a fever >38.9°C (>102.0°F) will be prompted to contact the 
investigator. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as applicable. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor).  The investigator or qualified designee will assess 
the fever and perform an unscheduled visit as appropriate.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as 
Grade 4, after clinical evaluation of the maternal participant, documentation from another 
medically qualified source (eg, emergency room or hospital record), or contact with the 
maternal participant or her parent(s)/legal guardian (if a minor).  Grade 4 fevers will be 
collected on the AE CRF and assessed by the investigator using the AE intensity grading 
scale as detailed in Section 10.2.4.
Temperature will be measured and recorded to 1 decimal place and then categorized during 
analysis as mild, moderate, or severe based on the intensity grading scale provided in
Table 6.
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Table 6.
Ranges for Fever
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fever
≥38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°C
a.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as Grade 4, 
after clinical evaluation of the maternal participant, documentation from another medically qualified 
source (eg, emergency room or hospital record), or contact with the maternal participant or her 
parent(s)/legal guardian (if a minor).  Grade 4 fevers will be collected on the AE case report form and 
assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant Participants
There are no protocol-required laboratory assessments.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 4.  Device deficiencies are covered in Section 8.3.9.
AEs will be reported by the maternal participant/parent(s)/legal guardian(s).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7).
Each maternal participant or her parent(s)/legal guardian (if a minor) and parent/legal 
guardian/legally authorized representative of an infant participant will be questioned about 
the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
Maternal Participants
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each maternal participant including her fetus begins from the time the maternal 
participant and her parent(s)/legal guardian (if a minor) provides informed consent, which is 
obtained before participation in the study (ie, before undergoing any study-related procedure 
and/or receiving investigational product), through and including a minimum of 28 calendar 
days after the last administration of the investigational product.
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In this study, the investigator and site staff will ensure the active elicitation and collection of 
safety events as detailed below:

The active collection period for nonserious AEs begins once informed consent has been 
provided and continues through a minimum of 28 calendar days after vaccination.

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

In addition, AEs occurring up to 48 hours after blood draws that are related to study 
procedures must be reported in the CRF.

Details of any MA-RTI will not be collected as AEs/SAEs from informed consent until 
the maternal participant completes the study, unless the investigator or an appropriate 
designee deems the event to be possibly related to the investigational product or to have
resulted in death as detailed in Section 8.1.2 and Section 8.1.3.
For maternal participants who are screen failures, the active collection period ends when 
screen failure status is determined.
Infant Participants
For the infant participant, the time period for actively eliciting and collecting safety events is 
detailed below:

The active collection period for nonserious AEs begins at birth and continues through and 
including a minimum of 28 calendar days after birth.

The active collection period for NDCMCs and SAEs begins at birth and continues 
through the last study visit.
o
Details of any MA-RTI will not be collected as AEs/SAEs from 72 hours after 
birth until the infant participant completes the study, unless the investigator or an 
appropriate designee deems the event to be possibly related to the investigational 
product or if the event resulted in death. See Section 8.1 for the reporting 
procedures for efficacy-related endpoints. Note: Details of the MA-RTI visit 
should be recorded in the eCRF.

In addition, AEs occurring up to 48 hours after blood draws or nasal swabs that are 
related to study procedures must be reported in the CRF.
For Both Maternal and Infant Participants
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
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For maternal participants, and parent(s)/legal guardian(s) of infant participants born to 
maternal participants, who withdraw from the study and withdraw consent for the collection 
of future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form.
Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the Vaccine SAE Reporting Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the Vaccine SAE Reporting Form, immediately upon awareness and under no 
circumstances should this exceed 24 hours.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy; 
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those that occur within 1 month after birth; or congenital 
anomaly* [in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal 
death]), the investigator should follow the procedures for reporting SAEs.  In addition, infant 
deaths after 1 month of age should be reported as SAEs.
Further follow-up may be requested by the sponsor and will be handled on a case-by-case 
basis (eg, follow-up on preterm infants to identify developmental delays).
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
The same is applied for those SAEs after the active collection period has ended, should they 
occur to the fetus.  In addition, infant deaths that occur after 12 months of age should be 
reported as SAEs when the investigator believes the SAE or death has at least a reasonable 
possibility of being related to investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.37
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8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All AEs/SAEs occurring in a participant during the active collection period, which begins 
after obtaining informed consent as described in Section 8.3.1, will be recorded on the AE 
section of the CRF.
The investigator is to record on the CRF all directly observed, and all spontaneously reported 
AEs and SAEs reported by the participant, or her parent(s)/legal guardian (if a minor) and
parent(s)/legal guardian(s) of infant participants born to maternal participants.
The investigator obtains general information on the pregnancy and its outcome for all study 
participants.  The investigator will follow the pregnancy until completion (or until pregnancy 
termination).  In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth.  In the event of a termination, the reason(s) for termination should be 
specified and, if clinically possible, the structural integrity of the terminated fetus should be 
assessed by gross visual inspection (unless preprocedure test findings are conclusive for a 
congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, stillbirth, neonatal death,
defined as those deaths that occur within 1 month after birth; or congenital anomaly* [in a 
live-born baby, a stillbirth, or a neonatal death]), the investigator should record this 
information in the CRF.  In addition, infant deaths after 1 month of age should be recorded in 
the CRF as SAEs.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.37
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.4).
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In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety.
Further information on follow-up procedures is given in Appendix 2.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
Potential efficacy endpoints on this study as defined in Section 8.1 will be excluded from the 
standard SAE reporting process unless deemed possibly related to investigational product.
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the 
Investigational Product
8.3.5.1. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Scenarios of exposure during breastfeeding for infants not delivered during the study must be 
reported, irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours 
of the investigator’s awareness, using the Vaccine SAE Reporting Form.  An 
exposure-during-breastfeeding report is not created when a Pfizer drug specifically approved 
for use in breastfeeding women (eg, vitamins) is administered in accord with authorized use.  
However, if the infant experiences an SAE associated with such a drug’s administration, the 
SAE is reported together with the exposure during breastfeeding.
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8.3.5.2. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
investigational product, which may or may not lead to the occurrence of an AE. Such 
persons may include HCPs, family members, and other roles that are involved in the trial 
participant’s care.
Note: This does NOT apply to maternal participants enrolled in this trial.
In addition, the scenarios below describe environmental exposures that could lead to an 
exposure during pregnancy (EDP):

A female becomes or is found to be pregnant, having been exposed (eg, because of 
environmental exposure) to the investigational product; or the female becomes or is 
found to be pregnant after being exposed to the investigational product;

A male has been exposed (eg, because of environmental exposure) to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the Vaccine SAE Reporting Form and the Exposure During Pregnancy 
Supplemental Form, as applicable, regardless of whether there is an associated SAE.  In the 
event of an EDP, the information submitted should include the anticipated date of delivery.  
Since the information does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the ISF.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
are as follows:

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
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completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.
8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
This section provides information on adverse events of special interest (AESIs) that may be 
detected during the study.
For infant participants38:

Preterm birth (born at <37 weeks’ gestation)

Birth weight 1001 to 2500 g

Developmental delay*

Positive viral (PCR or antigen-based) testing for SARS-CoV-2, when not reported 
during a MA-RTI visit, should be reported as SARS-CoV-2 test positive
The following AESIs are to be reported as SAEs:

Extremely preterm birth (<28 weeks)

Extremely low birth weight (≤1000 g)
For maternal participants:

Preterm delivery

Positive viral (PCR or antigen-based) testing for SARS-CoV-2, when not reported 
during a MA-RTI visit, should be reported as SARS-CoV-2 test positive
All AESIs must be reported as an AE or SAE following the procedures described in
Section 8.3.1 through Section 8.3.4 except the active collection period for AESIs is from the 
signing of the ICD until the end of the study for maternal participants and from birth until the 
end of the study for infant participants.
Notes: An AESI that is recorded as an SAE must be reported using the Vaccine SAE 
Reporting Form.
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*Developmental delay is to be assessed by clinical expertise using local guidelines for 
standard of care. Events identified as both an AESI and an NDCMC should be reported as an 
AESI in the CRF.
8.3.8.1. Lack of Efficacy
This section is not applicable for this study, as efficacy is yet to be demonstrated in the study 
population.
8.3.9. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 4.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 2 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 4.
8.3.9.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  Follow-up applies to all participants, including 
those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
Information will be provided to the sponsor as described in the IP manual.
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Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration by an incorrect route;
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
The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any additional dose of investigational product will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose in the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
No interruptions or dose modifications will be made in this study.
8.5. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
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8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Health Economics
Health economics will be evaluated in exploratory analyses assessing vaccine impact on 
healthcare resource utilization parameters evaluated during study visits, which may include 
the following: number and type of medical visits, length of hospital stay, requirement for 
mechanical ventilation, requirement for respiratory diagnostic procedures, requirement for 
IV fluids, requirement for prescriptions, and antibiotic use.
8.10. Procedures – Maternal Participants
8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to Vaccination to Day 1 –
Visit 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant or their parent(s)/legal 
guardian (if a minor). Each signature on the ICD must be personally dated by the signatory.
Maternal participants who might be illiterate must thumbprint the ICD and it must be signed 
and dated by an impartial witness who was present throughout the entire informed consent 
process before performing any study-related procedures.
The investigator or his or her designee will also sign and date the ICD.  A copy of the 
signed/thumbprinted and dated ICD must be given to the maternal participant and her 
parent(s)/legal guardian (if a minor).  The source data must reflect that the informed 
consent was obtained before participation in the study.
If the maternal participant is found ineligible for the study based on a full assessment of 
inclusion and exclusion criteria, the investigator may advise the participant and her 
parent(s)/legal guardian (if a minor), either by telephone or face to face, that the participant 
will be excluded from further participation in the study, as defined in Section 5.4.  All 
eligible maternal participants will proceed to complete the vaccination visit.
Standard-of-care procedures performed prior to informed consent can be considered for use 
in the study provided they follow guidance around the timing of procedures stipulated in the 
protocol.
In countries/locales where procedures to confirm maternal participant eligibility for
this clinical trial are not routinely performed, the procedures must be obtained and 
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.
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The following procedures will be performed:

Obtain written informed consent, and assent if appropriate, from the maternal participant
before performing any study-specific procedures. If the maternal participant is illiterate,
she must thumbprint the ICD and it must be signed and dated by an impartial witness 
who was present throughout the entire informed consent process.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity).  The date of birth will be 
collected to critically evaluate the immune response and safety profile by age.

Obtain and record current/former alcohol, tobacco, marijuana, or any illicit drug usage.

Obtain and record any medical, surgical, and obstetric history of clinical significance 
including history from prior and current pregnancy(ies).

Record the LMP and estimated delivery date (EDD).

Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.

Record the prepregnancy BMI in the source documentation. If the prepregnancy BMI is 
not available, record the BMI at the time of the first obstetric visit during the current 
pregnancy.

Perform targeted physical examination evaluating/noting any clinically significant 
abnormalities within the following body systems:
o
Mandatory - general appearance; heart; lungs; abdomen.
o
Discretionary - skin; head, eyes, ears, nose, and throat; musculoskeletal; extremities; 
neurological; lymph nodes.
Note: Significant medical and surgical history and abnormal observations from the 
physical examination will be documented and recorded in the CRF.

Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement.
o
Where an obstetric ultrasound examination is not performed at ≥18 weeks of 
pregnancy as part of prenatal standard of care, perform an ultrasound examination.
o
Note: Physical or obstetric examinations performed as standard of care may be 
admissible if performed within 7 days prior to the vaccination visit.
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
Obtain details of any Ig (including monoclonal antibodies or immune globulin [Rho(D) 
immune globulin, eg, RhoGAM]) or blood products (eg, whole blood, packed cells) given 
at any time during the current pregnancy.

Obtain details of any nonstudy vaccinations given at any time during the current 
pregnancy.

Obtain details of syphilis, HIV, and HBV status.
o
Note: Only participants with a documented negative syphilis test result and negative 
HIV antibody and HBV surface antigen test results obtained during the current 
pregnancy are eligible for randomization.
o
If not performed as standard of care, assessment should be performed as part of the 
study, locally, and vaccination of maternal participant should be deferred until the 
results are available and confirmed to be negative within 28 days prior to study 
randomization.

Ensure and document that all the inclusion criteria and none of the exclusion 
criteria are met.

Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.2.3.

Issue the maternal participant an e-diary and provide instructions on its completion
(if applicable).

Note: E-diary completion instructions may be provided to her parent(s)/legal 
guardian (if a minor).

Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures and provide instructions on their use to the maternal 
participant and her parent(s)/legal guardian (if a minor).

On the day of and prior to vaccination, ask the maternal participant to capture the 
baseline systemic event measurements in her e-diary or the site staff will capture the 
baseline systemic event measurements in the provisioned device (if applicable for 
illiterate participants).

Prior to vaccination, collect a blood sample of approximately 15 mL for serologic 
assessments (prevaccination blood collection should take place on the same day or within 
7 days before the vaccination visit).

Obtain the maternal participant’s randomization number and investigational product kit 
number using the IRT system. Refer to the IRT manual for further instructions on this 
process.
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
Qualified site staff member(s) will administer a single-vial dose of investigational 
product into the deltoid muscle of the (preferably) nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
Please refer to the IP manual for further instruction on this procedure.

Site staff must observe the maternal participant for any acute reactions for at least 
30 minutes after investigational product administration.

Record any acute reactions in the maternal participant’s source documents, on the AE 
page of the CRF, and on the Vaccine SAE Reporting Form as applicable.

Ask the maternal participant to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination, OR explain to the maternal participant that a study staff 
member/field worker will call or visit her every day from Day 2 to Day 7 after 
vaccination (where Day 1 is the day of vaccination) to collect or take her temperature and 
record systemic events, acute local reactions, and use of antipyretic medication in a diary
(if applicable).

Ask the maternal participant or her parent(s)/legal guardian (if a minor) to contact the site 
staff or investigator immediately if she experiences any of the following from Day 1 to 
Day 7 after vaccination to determine if an unscheduled reactogenicity visit is required as 
detailed in Section 8.10.5 OR inform the maternal participant or her parent(s)/legal 
guardian (if a minor) that if she experiences any of the following from Day 1 to Day 7 
after vaccination or is taking antipyretic medication at Day 7, then the study staff/field 
worker will continue to visit until resolution.  Furthermore, the maternal participant will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns as detailed in Section 8.10.5.
o
Fever ≥39.0°C (≥102.1°F).
o
Redness or swelling at the injection site measuring >20 measuring device units 
(greater than 10 cm).
o
Severe pain at the injection site.
o
Any severe systemic event.

Inform the maternal participants or her parent(s)/legal guardian (if a minor) that if a 
temperature of ≥38.0°C (≥100.4°F) is recorded during the collection of diary data, she 
will be required to have a rapid test for malaria as per local practice and details will be 
recorded in the diary (if applicable, based on local practice).

Remind maternal participants or her parent(s)/legal guardian (if a minor) that study staff 
may contact them to obtain additional information on events entered into the e-diary.
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
Remind maternal participants or their parent(s)/legal guardian (if a minor) to inform the 
study staff of any AEs and SAEs that occur for the duration of the trial as described in 
Section 8.2 and Section 10.2.

Remind the maternal participant or her parent(s)/legal guardian (if a minor) to bring the 
completed e-diary to the next visit (if applicable).

Complete the source documents.

The investigator or an authorized designee completes the CRFs, and the blinded 
dispenser/administrator completes the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.

Maternal participants or their parent(s)/legal guardian (if a minor) will be instructed to 
contact the site to report any significant illness (new or worsening), any medically 
attended respiratory events (eg, doctor’s visit, emergency room visit), or any 
hospitalization that occurs during the study period as detailed in Section 8.10.6.

Request the maternal participant and her parent(s)/legal guardian (if a minor) to contact 
the site if she goes into labor/is admitted to the maternal unit (The study staff/field worker 
will contact the maternal participant prior to the next study visit to remind her, if 
applicable).
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After Vaccination)
If delivery occurs before this visit, this visit will not be conducted.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

Review the participant’s e-diary data. Collect stop dates of any e-diary events ongoing 
on the last day that the e-diary was completed and record stop dates in the CRF.

Record details of any MA-RTI, including the diagnosis.

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.
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
Record AEs and SAEs as described in Section 8.2 and Section 10.2. Note: Active 
elicitation and collection of AEs and SAEs through 28 days after vaccination must occur 
even if delivery occurs within 28 days after vaccination.

The investigator or an authorized designee completes the CRF.

Maternal participants and their parent(s)/legal guardian (if a minor) will be instructed to 
contact the site to report any significant illness (new or worsening), any medically 
attended respiratory events (eg, doctor’s visit, emergency room visit), or any 
hospitalization that occurs during the study period as detailed in Section 8.10.6.

Request the maternal participant and her parent(s)/legal guardian (if a minor) to contact 
the site if she goes into labor/is admitted to the maternal unit (The study staff/field worker 
will contact the maternal participant prior to the next study visit to remind her, if 
applicable).
8.10.3. Delivery (Maternity Unit)
The delivery visit spans the time from when a participant is admitted in labor through 
discharge following delivery of her infant. Protocol-specified procedures associated with 
this delivery visit may be done at any time during this period.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

If available, record the maternal participant’s group B streptococcal (GBS) status and if 
any medication was given for intrapartum antibiotic prophylaxis (IAP). Note: Positive 
GBS carriage should not be reported as an adverse event in the CRF if performed in the 
setting of routine prenatal care.

Record details of any nonstudy vaccinations given since the last visit.

Collect a blood sample of approximately 15 mL for serologic assessments.  Note: The 
maternal participant’s blood sample can be taken at any time during the delivery visit, 
preferably before delivery. In the event that the blood sample cannot be obtained 
before delivery, the sample should be collected as close to delivery as possible and at 
most 48 hours postpartum.
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments 
must also be collected.  Cord blood is collected from the umbilical cord vein attached to 
the placenta prior to the blood clotting within the cord and after the umbilical cord has 
been clamped and cut.  This sample should be labeled with the infant’s participant ID 
number.
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
Record pregnancy outcome information, including vital status of the infant (live, 
stillbirth, etc.), mode of delivery (vaginal delivery or cesarean section), and the use of any 
assisted devices (forceps or vacuum).

Record details of any MA-RTI, including the diagnosis.

Record AEs as described in Section 8.2 and Section 10.2.

Ask the maternal participants and her parent(s)/legal guardian (if a minor) to contact the 
site to report any significant illness (new or worsening), any medically attended 
respiratory events (eg, doctor’s visit, emergency room visit), or any hospitalization that 
occurs during the study period as detailed in Section 8.10.6.

Ask the maternal participant and her parent(s)/legal guardian (if a minor) to contact the 
site staff or investigator if her newborn infant meets the MA-RTI study criteria OR the 
study staff/field worker will contact the maternal participant/legal guardian(s) weekly to 
remind them to report any MA-RTI (if applicable).

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 210 Days After 
Delivery)

Obtain details of any postnatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [eg, HBIG]) or Rho(D) immune globulin [eg, RhoGAM]) or blood 
products (eg, whole blood, packed cells) given since the last visit.

Record details of any nonstudy vaccinations given since the last visit.

Record details of any MA-RTI, including the diagnosis.

Ask the maternal participant and her parent(s)/legal guardian (if a minor) to contact the 
site staff or investigator if her infant meets the MA-RTI study criteria OR the study 
staff/field worker will contact the maternal participant/legal guardian(s) weekly to remind 
them to report any MA-RTI, if applicable.

Record AEs as described in Section 8.2 and Section 10.2.

Complete the maternal participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.10.5. Unscheduled Reactogenicity Visits
If the maternal participant or her parent(s)/legal guardian (if a minor) reports 1 or more of the 
following, a contact must occur as soon as possible between the maternal participant and the 
investigator, or a medically qualified member of the study site staff, to assess if an 
unscheduled reactogenicity visit is required OR based on local practice in certain 
countries/locales, maternal participants will be referred to the appropriate healthcare facility 
at the discretion of the study staff/field worker if there are any concerns regarding 
reactogenicity events, including:

redness at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

swelling at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

severe injection site pain on the arm that the investigational product was 
administered, 

fever ≥39.0°C (≥102.1°F).
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The maternal participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or

The participant/study staff/field worker recorded an incorrect value in the e-diary 
(confirmation of an e-diary data entry error), or

The investigator or appropriate designee determines that the visit is not required.
This contact will be recorded in the maternal participant’s source notes and in the CRF.
Any ongoing reactions must be assessed at the next scheduled visit.
The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure oral temperature.

Measure the participant’s heart rate.

Measure the participant’s blood pressure (seated).
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
Measure the minimum and maximum diameters of redness (if present) on the arm in 
which the investigational product was administered.

Measure the minimum and maximum diameters of swelling (if present) on the arm in 
which the investigational product was administered.

Assess if necrosis is present at the injection site on the arm in which the investigational 
product was administered.

Assess if any exfoliative dermatitis is present.

Assess any injection site pain on the arm in which the investigational product was 
administered that is present in accordance with the reactogenicity grading scale provided 
in Section 8.2.1.1.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 8.2.1.2.

Ask the participant or her parent(s)/legal guardian (if a minor) if she attended an 
emergency room visit or was hospitalized.

For severe pain at the injection site resulting in an emergency room visit or 
hospitalization, severe systemic events associated with an emergency room visit or 
hospitalization, any necrosis on the arm in which the investigational product was 
administered, or exfoliative dermatitis, the investigator or qualified designee must assess 
these events in accordance with the intensity AE grading scale provided in
Section 8.2.1.1 and Section 8.2.1.2.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

Complete the participant’s source documents.

The investigator or an authorized designee will complete the CRFs.

The study staff/field worker may contact the participant to obtain additional information 
on events entered into the e-diary, as appropriate.
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8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria – Maternal 
Participants

Starting from Day 1 after vaccination (where Day 1 is the day of vaccination) until the 
end of the study, all maternal participants will be monitored for MA-RTIs as detailed in 
Section 1.2.3.1 and Section 8.1.2. Maternal participants or their parent(s)/legal guardian 
(if a minor) should notify the site and/field worker of the occurrence of any MA-RTIs 
immediately but no later than the next study visit. Note: Site contact may be by an 
electronic method of communication (including but not limited to electronic messaging, 
short message service [SMS], text, email), by phone call, or by face-to-face contact.

The definition of maternal RTI includes 1 or more of the following signs and/or 
symptoms:
o
New or increased sore throat
o
New or increased cough
o
New or increased nasal congestion
o
New or increased nasal discharge
o
New or increased wheezing
o
New or increased sputum production
o
New or increased shortness of breath

Record the details of any MA-RTI, including the diagnosis, the medically attended visit 
location (hospital, outpatient visit, emergency room, urgent care, or home visit), duration 
of hospitalization, intensive care unit (ICU) duration if applicable, prescribed medications 
for the MA-RTI, assessments including RSV test result (eg, NAAT, rapid antigen 
detection tests, or any other molecular diagnostic test), if available, and the final 
diagnosis.

Record the details of any nonstudy vaccinations.

Record AEs as described in Section 8.2 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.11. Procedures – Infant Participants
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After Birth)

Manually assign a single infant participant identifier. This will be assigned manually by 
the site using the following convention: the infant participant’s identifier will be the 
maternal participant’s IRT-generated numeric ID but with the fifth digit changed to a 2 
(eg, if the maternal participant is given number 10011001, then the infant will be 
10012001).

Collect a cord blood sample of approximately 10 mL for immunogenicity assessments.  
Cord blood is collected from the umbilical cord vein attached to the placenta prior to the 
blood clotting within the cord and after the umbilical cord has been clamped and cut.  
This sample should be labeled with the infant’s participant ID number.

If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 24 hours, but up to 7 days after birth.  The volume of blood collected 
will be based on the weight of the infant (refer to Table 3).

Ensure and document that all the infant inclusion criteria and none of the infant exclusion 
criteria are met.

Collect demography (including complete date of birth [ie, dd-Mmm-YYYY], sex, race, 
and ethnicity).  The date of birth will be collected to critically address efficacy analyses
and evaluate the immune response and safety profile by age.
o
Obtain and record the infant’s length, head circumference, and weight at birth.
o
Obtain and record the infant’s birth data, including GA and appearance, pulse, 
grimace, activity, and respiration (Apgar) score.
o
Obtain and record background factors as described in Section 10.5.
o
Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.
o
Standard-of-care vital signs and examination procedures can be considered for use in 
the study provided they were performed within 72 hours after birth. Note: Please 
reference the physical examination procedures below for details.
o
Perform a physical examination, if not performed as part of standard of care, noting 
any clinically significant abnormalities within the following body systems: general 
appearance; skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; back; 
musculoskeletal; extremities; genitourinary; neurological; and lymph nodes.  
Abnormal results must be recorded on source documents as well as the physical 
examination pages of the CRF; only if the abnormal finding is deemed to be clinically 
significant should this be recorded on the AE pages of the CRF.
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o
Record details of any congenital anomalies on the AE page of the CRF, and report as 
an SAE as described in Section 10.2.3.

Record any medication as described in Section 6.5.6.

Obtain details of any Ig (including monoclonal antibodies [eg, Synagis] or immune 
globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given to the 
infant participant since birth.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Review the weekly contact schedule with the parent(s)/legal guardian(s) and collect 
contact information OR remind the parent(s)/legal guardian(s) that a field worker will 
contact them weekly to remind them to report any MA-RTI (if applicable).

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria. An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of this study visit.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate. Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the
study visit.
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
Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the site source documents. Newly 
identified abnormal findings must be recorded on source documents and, if considered 
clinically significant in the judgment of the investigator/examiner, on the AE page of the 
CRF. Note: Standard-of-care examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit.
o
Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee 
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria.  An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every 7 days 
from birth until the 6-month follow-up visit to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The weekly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.7.1 for guidance on reported cases of 
MA-RTIs in infant participants during the first 6 months after birth.
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8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.

Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.
Note: Standard-of-care examination procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.
o
Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants.

Ask the parent(s)/legal guardian(s) to contact the investigator immediately if any 
significant illness or hospitalization occurs or if the infant meets the MA-RTI visit
criteria.  An RTI study visit, along with a nasal swab collection, must be performed 
for all hospitalizations due to an RTI and severe MA-LRTIs as described in 
Section 1.2.4.1 and Section 8.11.8.
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If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care as 
described above, noting any clinically significant abnormalities in the source documents. 
Newly identified abnormal findings must be recorded on source documents and, if 
considered clinically significant in the judgment of the investigator/examiner, on the AE 
page of the CRF. Only applicable if a clinic visit is conducted. Note: Standard-of-care 
examination procedures can be considered for use at this study visit, if they were 
performed within the window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants except for infant participants born during the first year of the study.

The investigator or an authorized designee completes the CRF for infant participants born 
during the first year of the study. Note: An additional 12-month blinded follow-up period 
for longer-term RTI surveillance and safety oversight will be included for these 
participants.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Confirm the understanding of the infant participant’s parent(s)/legal guardian(s) 
regarding site contact for the study, which is approximately every month (28 to 35 days) 
until the end-of-study visit. Ask the parent(s)/legal guardian(s) to contact the 
investigational site/field worker promptly if the infant meets the MA-RTI visit criteria.  
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The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants.

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days After Birth; 
Infant Participants Born During the First Year of the Study Only)

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants.
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Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 742 Days After 
Birth; Infant Participants Born During the First Year of the Study)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if 
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care, noting 
any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF. 
Only applicable if a clinic visit is conducted. Note: Standard-of-care examination 
procedures can be considered for use at this study visit, if they were performed within the 
window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants born during the first year of the study.
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8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 Months After 
Delivery)

This is an active surveillance period spanning from birth through 6 months after delivery 
(Visit 3). Note: Reporting MA-RTI events should commence 72 hours after the infant’s 
delivery.  Respiratory distress events associated with and within 72 hours of birth should 
not be captured as MA-RTI events for the study but should be captured as AEs/SAEs 
(if applicable).

The sponsor may alter the frequency of the weekly contacts or the duration of 
surveillance for MA-RTI based on RSV surveillance data or other operational factors.
8.11.7.1. Study Visits Following a Medically Attended RTI – Hospital, Home, or Clinic 
Visit

Contact the infant participant’s parent(s)/legal guardian(s) approximately every week 
(7 to 10 days) from birth until Visit 3 (6-month follow-up visit), to remind the 
parent(s)/legal guardian(s) to contact the investigational site promptly if the infant meets 
the criteria for an MA-RTI event.  The weekly contact may be via the e-diary device or 
study-related mobile application, text, email, phone call, or face-to-face contact with the 
site staff/field worker. Please refer to Table 1 regarding clinical signs and symptoms that 
meet the study definition of an MA-RTI, and Section 1.2.4.1 for study-required 
assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by:
o
The infant caregiver during or within 10 days following the MA-RTI visit
OR
o
The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an event requiring a visit to a healthcare provider, the site staff 
and/field worker should confirm, based on information provided, whether the event meets 
the criteria for an MA-RTI. Please refer to Table 1 and Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

When an infant MA-RTI criterion is met or confirmed, the site/field worker will obtain 
records from the medically attended visit and record the healthcare information as 
detailed in Appendix 6.
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
When an infant MA-RTI criterion is met or confirmed, the infant participant will be 
seen as soon as possible and optimally within 72 hours or up to 10 days for an RTI study 
visit by the investigational site staff or qualified designee.

The infant participant may be seen either at the time of the MA-RTI, at home or at the 
study site (if discharged), or if the infant participant has been hospitalized or is receiving 
treatment at another medical facility, the site staff/field worker can conduct the RTI study 
visit at those facilities.
o
If the RTI study visit is not performed within 72 hours of the event, it should still be 
performed, including the collection of nasal swab specimens.
o
Targeted assessments at an RTI study visit include but are not limited to:
o
Respiratory signs: lower chest wall indrawing.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Nasal swab collection from the infant participant for testing at the central 
laboratory.
o
Body weight

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site/field worker if the infant’s 
illness worsens, or if the infant is hospitalized.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Compile the adjudication submission package for the event as detailed in Section 8.1.
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8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit Criteria

This is a long-term surveillance procedure for all infant participants from 6 months after 
delivery (Visit 3) until the last study visit.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) from Visit 3 (6-month follow-up visit) until the end-of-study visit, to 
remind the parent(s)/legal guardian(s) to contact the investigational site promptly if the 
infant meets the criteria for an MA-RTI visit.  The monthly contact may be via the 
e-diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by:

The infant caregiver during or within 10 days following the MA-RTI visit
OR

The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an MA-RTI, the site should obtain additional information and 
determine whether the event also meets the study definition of a severe MA-LRTI.

Note: Severe MA-LRTI is defined in Table 1.

The site/field worker will obtain records from the medically attended visit and record the 
healthcare information as detailed in Appendix 6.

When an infant MA-RTI criterion is confirmed and also meets the study definition of 
hospitalization due to an RTI or a severe MA-LRTI, the infant participant will be seen 
as soon as possible and optimally within 72 hours or up to 10 days for an RTI study 
visit that includes a nasal swab collection by the investigational site staff/field worker. 
The staff/field worker will obtain the nasal swab optimally within 72 hours or up to 
10 days of the event with the infant participant either at home (if discharged) or, if the 
infant participant has been hospitalized or receiving treatment at another medical facility, 
the site staff/field worker will conduct the visit at those facilities.

Note: Nasal swab collection from the infant participant is for testing at the central 
laboratory.
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A targeted RTI study visit will be required for all reported cases of hospitalization due to 
an RTI or severe MA-LRTI only, and this includes but is not limited to:
o
Respiratory signs: lower chest wall indrawing, failure to respond/unconsciousness.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Body weight

A targeted RTI study visit is not required for an MA-RTI event not meeting the definition 
of hospitalization due to an RTI or severe MA-LRTI.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the MA-RTI event, including emergency room or
hospitalization details with admission and discharge date (if applicable).

Record any medication as described in Section 6.5.6.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.  Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site if the infant’s illness worsens, 
or if the infant is hospitalized.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Compile the adjudication submission package for hospitalizations due to an RTI and 
severe MA-LRTI events only as detailed in Section 8.1.
8.12. Nasal Swab Collection
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI 
visit during the RSV surveillance period from 72 hours after delivery until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of an MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1).
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The nasal swab sample is to be collected as soon as possible and optimally within 72 hours or 
up to 10 days of an MA-RTI visit in either the infant participant’s home or a medical setting 
(eg, clinic, hospital, etc.) by the investigational site staff.
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), the 
nasal swab can be collected by the infant’s caregiver or the HCP assessing the infant 
(in addition to any samples obtained in the course of routine clinical care) for processing at a 
Pfizer central laboratory, as detailed in Section 8.11.7.1 and Section 8.11.8.
In the event that these restrictions prevent taking RTI study swabs at the investigational site, 
the infant’s caregiver will be given a study nasal swab collection kit including shipping 
instructions, to be used if necessary. The infant caregiver or the HCP assessing the infant 
during an MA-RTI visit may assist the investigational sites by collecting of the study nasal 
swab samples, as required.
Note: Investigational site staff will review the procedures for nasal swab sample collection 
and shipping instructions with each infant caregiver and ensure that he/she understands the 
appropriate procedures for collecting and packaging samples for shipment to the study site.
The process for nasal swab collection and transport to the Pfizer central laboratory via study 
sites is detailed in the ISF.
8.13. Communication and Use of Technology
In a study of this duration that is event-driven, it is vital to ensure that communication 
between the study site and the maternal participant and parent(s)/legal guardian(s) is 
maintained to ensure that endpoint events are not missed.  This study will employ various 
methods, tailored to the individual participant (maternal and/or infant participant), to ensure 
that communication is maintained, and study information can be transmitted securely.  Using 
appropriate technology, a communication pathway between the maternal participant and 
parent(s)/legal guardian(s) and the study site staff will be established.  The maternal 
participant and the parent(s)/legal guardian(s) may be able to utilize their own devices to 
access this technology, or use a device provided by the sponsor.  Traditional methods of 
telephone communication will also be available. The technology solution may facilitate the 
following:

Contact with the investigator.

The ability of the maternal participant/parent(s)/legal guardian(s) to report MA-RTI visits
associated with the infant participant.

An alert in the event that the maternal or infant participant is hospitalized.

Visit reminders.
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
Messages of thanks and encouragement from the study team.

A platform for recording local reactions and systemic events (e-diary).
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in an SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Estimands and Statistical Hypotheses
The null hypothesis to be tested concerns VE for the primary endpoints. The RSV vaccine 
will be compared to placebo, testing the hypotheses H0: VE ≤20% vs Ha: VE 20%. For all 
secondary efficacy endpoints, the RSV vaccine will be compared to placebo, testing the 
hypotheses H0: VE ≤0% vs Ha: VE >0%. Hypothesis testing of the secondary endpoints is 
conditional upon rejection of the null hypothesis for at least 1 of the primary endpoints.
9.1.1. Estimands – Infant Participants
9.1.1.1. Efficacy
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with key protocol criteria (evaluable participants):

VE, defined as the percentage relative risk reduction in the incidence of MA-LRTI due to 
RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of severe MA-LRTI 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of hospitalization 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of all-cause 
MA-LRTI in the RSV vaccine group, relative to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  For participants who 
discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
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9.1.1.2. Immunogenicity
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with the key protocol criteria (evaluable participants):

Functional antibody levels estimated by the GMT for RSV A and RSV B serum
neutralizing titers.

Geometric mean ratio (GMR), estimated by the ratio of the GMTs for RSV A and RSV B
serum neutralizing titers of the RSV vaccine group to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as missing completely at random (MCAR) is assumed.  For participants 
who discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.3. Safety
In infant participants born to the maternal participants receiving 1 dose of investigational 
product:

The percentage of infant participants with specific birth outcomes.

The percentage of infant participants having AEs from birth through 1 month of age.

The percentage of infant participants having SAEs, NDCMCs, and new diagnosed 
congenital anomalies from birth through the last study visit.
Missing AE dates and missing AE intensity will be handled according to Pfizer safety rules.
9.1.2. Estimands – Maternal Participants
9.1.2.1. Immunogenicity
In maternal participants receiving 1 dose of investigational product and in compliance with 
the key protocol criteria (evaluable participants):

The immune response, estimated by the GMT for RSV A and RSV B serum neutralizing 
titers.

The immune response, estimated by the GMFR from baseline in RSV A and RSV B 
serum neutralizing titers.

GMR, estimated by the ratio of the GMTs for RSV A and RSV B serum neutralizing 
titers of the RSV vaccine group to the placebo group.
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
Geometric mean of the IgG levels against RSV prefusion F.

Geometric mean of the Ig levels to nonvaccine RSV antigens.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed. Missing serology results 
will not be imputed, as MCAR is assumed.  For participants who discontinue from the study 
or have major protocol violations, all postdiscontinuation or postviolation observations will 
be censored.
9.1.2.2. Safety
In maternal participants receiving 1 dose of investigational product:

The percentage of maternal participants reporting AEs through 1 month after vaccination.

The percentage of maternal participants reporting obstetric complications and SAEs 
through the end of the study.

The percentage of maternal participants reporting local reactions within 7 days of 
vaccination.

The percentage of maternal participants reporting systemic events within 7 days of 
vaccination.
Missing e-diary data will not be imputed; missing AE dates and missing AE intensity will be 
handled according to Pfizer safety rules.
9.2. Sample Size Determination
This is an event-driven study. Sample size is determined as the number of participants to be 
randomized that is expected to accrue the required number of endpoint cases in the evaluable 
population. In this study there are 2 primary endpoints, and success on either primary 
endpoint is sufficient (see Section 9.1); power for the study overall is therefore at least as 
high as the power for either primary endpoint individually. In order for the study to have at 
least 90% power to reject the null hypothesis for MA-LRTI due to RSV when true VE is 
60%, a total of 124 cases of MA-LRTI due to RSV within 90 days of birth are required in the 
evaluable population. This also accounts for potential use of an alpha of 1.25% 1-sided 
within the multiplicity adjustment. There is no explicit case target for the endpoint of severe 
MA-LRTI due to RSV; depending on the assumed true VE, power for that individual 
hypothesis may be lower, but the power for the primary endpoint family will be at least 90%. 
Hypotheses about VE may be restated as hypotheses about the proportion of cases in the 
RSV vaccine group, conditional upon a fixed total number of cases. If this proportion is p, 
the null hypothesis H0: VE ≤20% is equivalent to H0: p ≥0.444; the assumption of VE = 60% 
corresponds to p = 0.286. Power was evaluated by the exact binomial test, and the case 
target established as that number k for which power is guaranteed to be at least 90%, for all 
k* ≥k. The calculation accounted for the study design (1:1 randomization of participants to 
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RSV vaccine : placebo), planned interim analyses of efficacy (see Section 9.5), and an 
overall type 1 error of 2.5% 1-sided across the 2 primary endpoints.
This global study is planned to be conducted in the US and other high-income countries as 
well as LMICs. Incidence rates of the primary endpoints are expected to vary in different 
regions. Based on a recently completed Phase 3 trial of an RSV vaccine, the assumed 
incidence rate for MA-LRTI due to RSV through 90 days in low-incidence countries, such as 
the US, is approximately 1.75%; and in other regions is approximately 3.90%. With these 
assumptions, and also allowing for 60% VE and 10% of enrolled participants being 
nonevaluable, enrollment of approximately 6900 participants is planned for the study as a 
whole. The exact number of participants required to accrue the case target may be higher or 
lower than this, depending on incidence rates, observed VE, and the proportion of evaluable 
participants.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined for infant and maternal 
participants:
Population
Description
Enrolled
All maternal participants who sign the ICD.
Randomly assigned to 
investigational product
All maternal participants who are assigned a randomization 
number in the IRT system.
Evaluable efficacy –
infant (per-protocol)
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized at least 14 days prior to delivery, did not 
receive palivizumab or another monoclonal antibody targeting 
RSV, have no major protocol violations, and did not have 
transfusions of more than 20 mL/kg of any blood products at 
<180 days.
Modified intent-to-treat 
(mITT) efficacy – infant
All infant participants who are born to vaccinated maternal 
participants.
Evaluable 
immunogenicity – infant
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized, have blood drawn for assay testing 
within the specified time frame, have valid and determinate 
assay results for the proposed analysis, and have no major 
protocol violations.
Evaluable 
immunogenicity –
maternal
All maternal participants who are eligible, receive the 
investigational product to which they were randomized, have 
blood drawn for assay testing within the specified time frame, 
have valid and determinate assay results for the proposed 
analysis, and have no major protocol violations.
mITT immunogenicity –
infant
All infant participants who are born to vaccinated maternal 
participants and have at least 1 valid and determinate assay 
result for the proposed analysis.
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Population
Description
mITT immunogenicity –
maternal
All randomized maternal participants who receive 
investigational product and have at least 1 valid and determinate 
assay result for the proposed analysis.
Safety – infant
All infant participants who are born to vaccinated maternal 
participants.
Safety – maternal
All randomized maternal participants who receive 
investigational product.
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock for the first planned analysis 
and will describe the participant populations to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data.  This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The analysis of efficacy will use a conditional exact test based on the 
binomial distribution of the number of disease cases in the RSV vaccine 
group, given the total number of cases in both groups. The incidence of 
MA-LRTI due to RSV and severe MA-LRTI due to RSV in infant 
participants will be evaluated in both groups up to 90 days, 120 days, 
150 days, and 180 days after birth.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.

The 2 primary endpoints of MA-LRTI due to RSV and severe 
MA-LRTI due to RSV will be tested in parallel using a multiplicity 
adjustment procedure. Success of the trial requires rejection of the null 
hypothesis (ie, a CI lower bound >20%) for either one of the 2 primary 
endpoints.

The primary endpoint of severe MA-LRTI due to RSV may be demoted 
to a secondary endpoint if there are insufficient cases for an adequately 
powered analysis.  During the trial, blinded accrual of cases will be 
monitored and prior to any unblinding, a decision rule for this change 
will be established based on the total number of cases of severe 
MA-LRTI due to RSV.

Testing of the 2 primary endpoints across the time intervals will follow a 
fixed sequence with a gatekeeping strategy. First, the hypothesis 
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Endpoint
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pertaining to the incidence of the 2 primary endpoints within 90 days 
after birth will be tested, at the full multiplicity-adjusted alpha level, 
using a multiplicity adjustment for the 2 endpoints. If that null 
hypothesis cannot be rejected, testing ends. Otherwise, testing proceeds 
to the incidence within 120 days after birth. Only primary endpoint(s)
that are successful at all earlier time intervals will be considered at 
subsequent intervals. Testing will proceed to the endpoints evaluated at 
150 days and 180 days, conditional on rejection of the null hypotheses
for all earlier time intervals. Refer to the SAP for full details of the 
testing sequence and multiplicity correction strategy.

There may be up to 2 interim analyses of the MA-LRTI-due-to-RSV
endpoint when there is an adequate number of cases (at least 43 cases
within 90 days). Based on the fraction of cases included in an interim 
analysis, an alpha level will be derived based on a Lan-DeMets
implementation of the O’Brien-Fleming alpha spending function. For 
example, if there are 2 interim analyses at 43 cases and 62 cases, the 
appropriate 1-sided significance levels are 0.00014 at the first interim 
analysis, 0.0015 at the second interim analysis, and 0.0245 at the final 
analysis.  Implementation of these 1-sided significance levels ensures the 
overall type 1 error for the primary endpoint will be no more than 0.025.  
See Section 9.5 for more details.

At the interim analyses there will also be an assessment for futility, based 
on conditional power for the MA-LRTI-due-to-RSV endpoint. If the 
probability of success at the end of the trial is low, given the interim 
analysis results and the initially assumed VE is applied to the remaining 
data, consideration will be given to stopping the study for futility.

CIs for VE will be calculated using the appropriate multiplicity-adjusted 
alpha level α. If the lower 100(1 - α)% confidence limit for VE exceeds 
20%, the null hypothesis for that endpoint will be rejected.

At the end of the trial, the RSV vaccine may be deemed efficacious if 
there are 42 or fewer cases of MA-LRTI due to RSV in the RSV vaccine 
group out of the 124 total endpoint cases.  This corresponds to an 
estimated VE = 49%, with a 97.6% CI = (21%, 68%). For severe 
MA-LRTI, assuming a total of 50 cases occur, the vaccine may be 
deemed efficacious if there are 13 or fewer cases in the RSV vaccine 
group.  This corresponds to an estimated VE = 65%, with a 97.6% 
CI = (26%, 85%). For both of these examples, it is assumed a 1-sided 
alpha of 0.01225 applies to the endpoint in question. 
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Endpoint
Statistical Analysis Methods

Kaplan-Meier curves showing accrual of endpoint cases over 180 days 
will be presented.

There will be a sensitivity analysis of the primary endpoints to examine 
the impact of missing RSV swab results. Details are provided in the 
SAP.
Secondary

The analysis of secondary efficacy endpoints will use the exact 
conditional binomial method, as for the primary endpoint. Secondary 
endpoints will be examined at the final analysis only. VE will be 
estimated along with 2-sided 95% CI.

Inference for the secondary endpoints will be conditional upon 
demonstrating success for one of the primary efficacy endpoints. The 
secondary endpoints of hospitalizations due to RSV, all-cause MA-LRTI, 
and MA-LRTI beyond 180 days will be tested in parallel so as to 
preserve the overall type 1 error across primary and secondary endpoint 
families at no more than 2.5% 1-sided. Multiplicity correction strategies 
will be defined in the SAP. VE will be evaluated sequentially at 90 days, 
120 days, 150 days, 180 days, and 360 days for hospitalization due to 
RSV and all-cause MA-LRTI and at 210 days, 240 days, 270 days, and 
360 days for MA-LRTI due to RSV. Testing will only proceed to later 
time points conditional on success of all previous time points.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.
Exploratory

The incidence in infant participants of MA-RTIs due to RSV with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized.

The incidence in infant participants of MA-RTIs due to any cause with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized. All MA-RTIs and severe MA-LRTIs will be summarized 
separately.

The incidence in infant participants of MA-LRTIs due to RSV occurring 
361 to 730 days after birth will be summarized.

The incidence in infant participants of severe MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized.
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Endpoint
Statistical Analysis Methods

The incidence in infant participants of hospitalization due to RSV 
occurring 181 to 730 days after birth will be summarized.

The primary endpoint through 180 days after birth will be summarized 
separately as cases associated with RSV subgroup A or RSV subgroup B 
infection.

The primary endpoint through 180 days after birth will be summarized 
by interval from vaccination to delivery and by GA at the time of 
vaccination.

The incidence of MA-RTI, MA-LRTI, and severe MA-LRTI due to RSV 
occurring 0 to 730 days after birth in premature infants (<37 weeks GA) 
will be summarized.

The incidence of MA-RTI due to any cause in maternal participants from 
vaccination through 180 days after delivery will be summarized.
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

A 3-tier approach will be used to summarize AEs. For both Tier 1 and 
Tier 2 events, the 95% CIs for the difference in the percentage of 
participants reporting the events between the RSV vaccine group and the 
placebo group will be calculated using the test statistic proposed by 
Miettinen and Nurminen; in addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in the percentage of 
participants reporting the events, based on the same test statistic and under 
the assumption that the test statistic is asymptotically normally distributed.  
A Medical Dictionary for Regulatory Activities (MedDRA) preferred term 
is defined as a Tier 2 event if there are 1% or more participants in at least 
1 vaccine group reporting the event.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
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dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Secondary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Exploratory 
Subgroup analyses of safety will be performed based on age at vaccination 
(18 years, ≥18 years). These and other exploratory analyses will be 
described in the SAP, finalized before first database lock.
9.4.3. Other Analyses
9.4.3.1. Immunogenicity Analyses
Immunogenicity endpoints are exploratory in the study.  The analyses of immunogenicity 
endpoints will be based on the evaluable populations.  An additional analysis will be 
performed based on the mITT populations if there is enough difference between the mITT 
populations and the evaluable populations.  Immunogenicity data for maternal participants 
and infant participants will be summarized separately, with the exception of 
maternal-to-infant placental transfer analysis.  Participants will be summarized according to 
the vaccine group to which they (for maternal participants) or their mothers (for infant 
participants) were randomized.
The secondary and exploratory immunogenicity endpoints will be described by the following 
summaries and the 95% CIs:

GMT of the RSV A and RSV B serum neutralizing titers at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMT of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMFR for RSV A and RSV B serum neutralizing titers from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).
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
GMFR of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMR of the RSV vaccine group to the placebo group for the RSV A and 
RSV B serum neutralizing titers at each available time point after vaccination (maternal 
participants and infant participants, separately).

GMR of the RSV vaccine group to the placebo group for the combined RSV A/B serum
neutralizing titers at each available time point after vaccination (maternal participants and 
infant participants, separately).

Geometric mean of the IgG levels against RSV prefusion F and Ig levels to nonvaccine 
RSV antigens at each available time point by vaccine group (maternal participants and 
infant participants, separately).
Empirical reverse cumulative distribution curves (RCDCs) for combinations of time points 
and vaccine groups will be presented for RSV A and RSV B serum neutralizing titers.
A sensitivity analysis will be performed to exclude immunogenicity data from mothers and 
their infants following onset of RSV infection between vaccination and delivery (based on 
evidence from the nonvaccine antigen assay).
Subgroup analyses of the secondary and exploratory immunogenicity endpoints will be 
performed, including an analysis based on GA at the time of vaccination, age at vaccination 
(18 years, ≥18 years), time from vaccination to delivery, and by country subcategories. All 
subgroup analyses will be defined in the SAP.
In addition, the maternal-to-infant placental transfer ratio (infant/mother) of RSV A and 
RSV B serum neutralizing titers and associated 95% CI will be summarized.
9.4.3.2. Healthcare Utilization Analyses
Healthcare utilization endpoints are exploratory in the study; these analyses will be described 
in the SAP and finalized before first database lock. For these analyses, details of healthcare 
resource utilization for all infants will be assessed at each MA-RTI visit from 72 hours after 
the infant’s delivery through the last study visit (730 days after birth). Univariate summaries
of healthcare resource utilization variables will be compared between the RSVpreF and 
placebo groups. The summarized variables may include the following: number and type 
(eg, respiratory, reactive airway disease [RAD]/asthma/wheezing) of medical visits 
(eg, outpatient, urgent care, emergency room, hospitalization, ICU), length of hospital stay, 
requirement for mechanical ventilation (yes/no, total number of episodes, total number of 
hours/days on treatment), requirement for IV fluids, requirement for respiratory diagnostic 
procedures (eg, chest radiograph, supplemental oxygen, pulse oximetry), requirement for 
prescriptions (eg, total number of prescriptions, selected respiratory medications 
[eg, bronchodilators, corticosteroid therapy, racemic epinephrine]), and antibiotic use 
(eg, total number of prescriptions, number of use days).
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9.5. Interim Analyses
Interim analyses may be performed to assess efficacy and safety after at least 43 cases of 
MA-LRTI due to RSV within 90 days have occurred. Because of the relatively low number 
of cases of severe MA-LRTI due to RSV expected, the interim analyses may not consider 
that endpoint. Interim analysis results may be used for internal business decisions regarding 
future study planning, stopping for futility, or stopping for early success.
The order of cases included in the interim analysis will be determined by the adjudication 
committee as those first confirmed as meeting the protocol-defined criteria. When the target 
number of cases for an interim analysis is reached, it is possible that additional potential 
cases will be under adjudication. Only cases that have been fully adjudicated prior to taking a 
data snapshot will be included in an interim analysis.
The analysis of efficacy will utilize an O’Brien-Fleming alpha spending rule based on the 
fraction of cases of MA-LRTI due to RSV within 90 days available. The exact number of 
cases at each interim analysis is not fixed and may be decided based on operational reasons. 
However, no fewer than 43 cases will be included in the first interim analysis, and no fewer 
than 62 cases will be included in the second interim analysis. For example, to control the 
overall type 1 error for the primary endpoint at 2.5% 1-sided, a first interim analysis at 
43 cases would use a 1-sided significance level of 0.014%.  If a second interim analysis was 
performed, for example, at 62 cases, it would use a 1-sided significance level of 0.15%. The 
final analysis at the target number of cases would use a 1-sided significance level of 2.45%.  
The alpha levels used at interim and final analyses will depend on the exact fraction of cases 
available at the interim analysis.
Testing of the primary endpoints at the interim analysis will follow the sequence of 
interval-specific tests as described in Section 9.4.1.  Secondary endpoints will not be tested at 
the interim analysis.
Futility will also be assessed using conditional power. Full details will be defined in the 
SAP. For example, if there are 62 cases available for the interim analysis, Table 7 indicates 
case splits for which stopping the study will be considered. The actual number of cases 
available may be slightly higher or lower than 62, and the decision rules amended 
accordingly.
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Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals at an 
Interim Analysis
Total Cases
RSV Vaccine 
Group Cases
Placebo Group 
Cases
VE (CI)a
Notes
43 (First interim)
24
19
-26% (-145%, 34%)
Conditional power 
<20%,b possible 
futility declaration
43 (First interim)
6
37
84% (27%, 98%)
Maximum number 
of vaccine group
cases permitted to 
declare VE >20%
62 (Second interim)
29
33
12% (-49%, 49%)
Conditional power 
<20%,b possible 
futility declaration
62 (Second interim)
14
48
71% (25%, 91%)
Maximum number 
of vaccine group
cases permitted to 
declare VE >20%
Abbreviation: VE = vaccine efficacy.
a.
Confidence level for efficacy declaration based on half the available alpha at each interim, assuming both
MA-LRTI and severe MA-LRTI endpoints were inspected; 95% confidence level for futility.
b.
Other conditional power levels may be considered as a trigger for a futility decision.
Before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan, and method of maintaining the study blind as per Pfizer’s standard 
operating procedures (SOPs) will be documented and approved in the DMC charter.  In 
addition, the analysis details must be documented and approved in an interim analysis SAP 
or final SAP.
9.5.1. Data Monitoring Committee
This study will use an E-DMC.  Refer to the E-DMC charter for further details.
The E-DMC will review safety data at defined intervals as specified in the charter.  The 
E-DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.
The E-DMC may review unblinded data during closed meeting sessions; however, the 
sponsor will remain blinded and will not be permitted access to the randomization 
assignments until the database is locked and unblinded.
After each meeting, the E-DMC will make recommendations that may include continuing the 
study with or without modification or pausing or stopping vaccination for safety or other 
reasons.
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The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints, to regulatory authorities, as appropriate.
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
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10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the maternal 
participant and her parent(s)/legal guardian (if a minor) and answer all questions regarding 
the study.
Maternal participants must be informed that their participation is voluntary.  Maternal 
participants and their parent(s)/legal guardian (if a minor) will be required to sign a statement 
of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant and her parent(s)/legal guardian (if a 
minor) is fully informed about the nature and objectives of the study, the sharing of data 
related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data.
The participant and her parent(s)/legal guardian (if a minor) must be informed that his/her 
personal study-related data will be used by the sponsor in accordance with local data 
protection law.  The level of disclosure must also be explained to the participant.
The participant and her parent(s)/legal guardian (if a minor) must be informed that his/her
medical records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities.
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The investigator further must ensure that each study participant or his or her parent(s)/legal 
guardian(s) is fully informed about his or her right to access and correct his or her personal 
data and to withdraw consent for the processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants and parent(s)/legal guardian(s) must be reconsented to the most current version 
of the ICD(s) during their participation in the study.
A copy of the ICD(s) must be provided to the maternal participant or the parent(s)/legal 
guardian(s).
A study-specific assent form will be provided to maternal participants denoted to be “minor 
participants” as required by local regulations.  It is to be understood as the “minor” maternal 
participants will participate in a trial after having received age-appropriate information and is 
sometimes also referred to as “knowing agreement.”  If the study includes minor participants 
who reach the age of majority during the study, as recognized under local law, they must 
reconsent as adults to remain in the study.  If the enrollment of emancipated minors is 
permitted by the study age criteria, the IRB/EC, and local law, they must provide 
documentation of legal status to give consent without the permission of a parent or legal 
guardian.
Before any study-specific activity is performed, the investigator, or a person designated by 
the investigator, will obtain written informed consent from each maternal participant and her 
parent(s)/legal guardian (if a minor).  This will include written informed consent for the 
mother and the fetus during the pregnancy, and the infant’s continuation in the study after 
delivery.  Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements.
Participants and their parent(s)/legal guardian (if a minor) who are rescreened may be 
required to sign a new ICD as per IRB, local regulations, etc.
If during the study, the investigator determines that the maternal participant is for any reason 
no longer capable of providing informed consent, the infant’s continued participation in the 
study requires consent to be obtained from the parent(s)/legal guardian as determined by 
local regulations, legal requirements, and the IRB/EC.
Note: For the infant participant, the term parent(s)/legal guardian denotes the “legally 
authorized representative.”
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10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT)/Clinical Trial Information System (CTIS), and/or www.pfizer.com, and 
other public registries in accordance with applicable local laws/regulations.  In addition, 
Pfizer reports study results outside of the requirements of local laws/regulations pursuant to 
its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted.  These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT/CTIS
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements.
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www.pfizer.com
Pfizer posts clinical study report (CSR) synopses and plain language study results summaries 
on www.pfizer.com for Pfizer-sponsored interventional studies at the same time the 
corresponding study results are posted to www.clinicaltrials.gov. CSR synopses will have 
personally identifiable information anonymized.
Documents Within Marketing Applications 
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized.
Data Sharing
Pfizer provides researchers secure access to participant-level data or full CSRs for the 
purposes of “bona-fide scientific research” that contribute to the scientific understanding of 
the disease, target, or compound class.  Pfizer will make data from these trials available 
24 months after study completion.  Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations.  CSRs will have personally identifiable 
information anonymized.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
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Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan/contracts.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
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Definition of what constitutes source data can be found in the site Source Data Agreement 
Plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study 
(or study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
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The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements.
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
For maternal immunization clinical studies conducted in pregnant women, data on the EDP
including any SAEs/nonserious AEs as well as pregnancy outcomes are collected and 
analyzed in the clinical database. All SAEs are reported to Pfizer Safety using the Vaccine 
SAE Reporting Form. In case of a new pregnancy in a maternal participant before the end of 
the study, any exposure to the investigational product is reportable to Pfizer Safety within 
24 hours of investigator awareness using the Vaccine SAE Reporting Form/EDP 
supplemental form.
The term “participant” in this section refers to (1) the maternal participant and her fetus; and 
after delivery (2) the maternal participant and (3) the infant participant.
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10.2.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.
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Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, cesarean section, endoscopy, appendectomy): the 
condition that leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.2.2. Newly Diagnosed Chronic Medical Conditions
An NDCMC is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
10.2.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting.  Complications that occur during hospitalization are AEs.  If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious.  When in 
doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
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d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a Pfizer 
product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited 
cases by pharmacovigilance personnel.  Such cases are also considered for reporting as 
product defects, if appropriate.
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10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording safety events on the CRF and 
for reporting safety events on the Vaccine SAE Reporting Form to Pfizer Safety.  These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and 
(3) occupational exposure.
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE 
Reporting Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study via 
occupational exposure
Occupational exposure is 
not recorded.
Occupational exposure 
(regardless of whether 
associated with an AE)
Note:  Include all AEs/SAEs 
associated with occupational 
exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.
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AE and SAE Recording/Reporting

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING
to describe the maximum intensity of the AE. For purposes of 
consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent 
intervention indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.
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Assessment of Causality

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused the 
event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible.  This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any anonymized 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.
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Follow-up of AEs and SAEs

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.2.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
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are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT values 
>2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
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hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with International 
Organization for Standardization (ISO) 14155.
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.4.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational medical device.  
This definition includes events related to the investigational medical device or 
comparator for study participants, users, and other persons.  This definition also 
includes events considered related to procedures for study participants only.

An ADE is defined as an AE related to the use of an investigational medical device.  
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
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10.4.2. Definition of Serious Adverse Event, Serious Adverse Device Effect, and 
Unanticipated Serious Adverse Device Effect
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is an AE that:
a. Led to death.
b. Led to serious deterioration in the health of the participant, that either resulted 
in:

A life-threatening illness or injury.  The term “life-threatening” in the definition of 
serious refers to an event in which the participant was at risk of death at the time of 
the event. It does not refer to an event that hypothetically might have caused death, 
if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
SADE Definition

A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE.
Unanticipated Serious Adverse Device Effect (USADE) Definition

A USADE is a serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis management 
file.
10.4.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance.  Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
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10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator 
to review all documentation (eg, hospital progress notes, laboratory reports, and 
diagnostic reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information in 
the participant’s medical records, in accordance with the investigator’s normal clinical 
practice and on the appropriate form of the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of following the reporting process described in the IP 
manual.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
“severe” should not be confused with an SAE. “Severe” is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as “severe.”

An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as “severe.”
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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE/device deficiency.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the medical 
notes that he/she has reviewed the AE/SAE/device deficiency and has provided an 
assessment of causality.

There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE/SAE/Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE/SAE/ device deficiency as fully as 
possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally completed CRF.
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Follow-up of AE/SAE/Device Deficiency

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.4.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.4.6. Reporting of SADEs
SADE Reporting to Pfizer Safety
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.
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10.5. Appendix 5: Background Factors
1. Information on the following will be collected at Visit 1, Visit 4 (12-Month), and 
Visit 6 (24-Month) for all infant participants:

Educational level of parent(s) or legal guardian(s).

Exposure to smoke (including tobacco smoke).

Number of persons in the household ≥18 years of age.

Number of children <18 years of age in the household and if they attend school/ 
daycare.
o
Number of children in the household under 5 years of age (under 60 months).
o
Number of children in the household ≥5 years of age (≥60 months).
2. Information on the following will be collected at each postbirth visit:

Childcare/daycare (for infant participants).

Breastfeeding information (including whether or not breastfeeding is exclusive).
3. Information on the following will be collected at each RTI study visit:

Number of missed days of work for parent(s) or legal guardian(s) due to the infant 
participant’s illness.
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria Checklist 
for MA-RTI Visit – Infant Participants
When an infant MA-RTI medical visit criterion is met or confirmed, the site will obtain 
records from the medical visit and capture the healthcare information as detailed below in the 
eCRF. This information is based on respiratory-related assessments including examination 
findings, clinical findings, and any pathogen-related assessments/findings.
Medical Visit - Visit Details and Assessment Requirements
Note: This should not be linked to a study visit but may overlap with the RTI study visit. 
The following fields and clinical assessment details should be obtained from relevant 
records for the medically attended event prior to each RTI study visit to support the 
assessment of the RTI event.

Reason for visit including date/time, eg,
o
Nasal discharge for 24 hours or more.
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o
Difficulty breathing, labored breathing, or rapid breathing for any duration.
o
Cough.
o
Inability to feed for any duration due to respiratory symptoms.
o
Apnea.
o
Any other respiratory symptom of concern.

Location of medical visit (inpatient clinic, outpatient clinic, emergency department, 
urgent care, hospitalization, home visit, other). Note: study visits should NOT be 
recorded here.
o
If hospital visit, was this triggered by an RTI (include details pertaining to duration
as well as admission and discharge information and records)?

Clinical findings pertaining to respiratory symptoms and/or RTI, as detailed below but 
not limited to:
o
Presence or absence of pertinent examination findings, eg, apnea (documented as per 
chart), wheezing, fever, cough, nasal congestion, intercostal retractions, lower chest 
wall indrawing, grunting, crackles, decreased breath sounds, other abnormal breath 
sounds, dry mucous membranes, skin tenting, sunken fontanelle, difficulty feeding, 
failure to respond/unconsciousness, etc.
o
Respiratory rate from highest/worst value of visit.
o
Oxygen saturation (SpO2) from lowest/worst value of visit.
o
Oxygen supplementation (assisted ventilation, including type of respiratory assistance 
[respirator, “state-of-the-art” occlusive nasal prongs, face tent, etc.]).

Days of supplementary oxygen.

Use of nasal cannula.

Use of high-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive).
o
Heart rate from worst value of visit when performed consistently.
o
Body weight from the date of the MA-RTI event.
o
Temperature from worst value of visit when performed consistently.
o
Additional clinical or respiratory related assessments including chest x-ray.
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
Local test results for RSV as part of routine clinical care:
o
Testing platform used (clinical list of all platforms and validated by research).
o
Result (list: positive, negative, indeterminate, other).

Results for any local non-RSV respiratory pathogen testing conducted as part of routine 
clinical care:
o
Result (list: detected, not detected, indeterminate)

Record the provider diagnosis, including any causative pathogen (if applicable), eg, RSV 
bronchiolitis, asthma, influenza, etc.

Obtain details of all prescribed medications including IV fluid usage.

Obtain details of all AEs/SAEs in line with study requirements. Note: MA-RTIs are not 
AEs/SAEs, unless related to the investigational product or resulting in death.
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10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
10.7.1. Informed Consent for the Maternal Participants <20 Years Old
Informed consent for maternal participants <20 years old and their infant participants will be 
obtained based on current Japanese civil code article 753 until 01 April 2022.

Married maternal participants 16 to <20 years of age are deemed to have reached 
“majority” and each maternal participant will sign the ICD for her and her infant’s study 
participation.

The maternal participants 16 years of age and unmarried maternal participants 16 to 
20 years of age are deemed “minors.”

When the maternal participant is a minor under local law, the investigator, or a person 
designated by the investigator, will obtain written informed consent from the maternal 
participant’s legally acceptable representative, parent(s), or legal guardian as well as 
the maternal participant’s assent (affirmative agreement) for her and her child’s study 
participation before any study-specific activity is performed. The investigator will 
retain the original of each signed consent and assent document.
o
The assent form for a minor must be in compliance with ICH GCP, local
regulatory requirements, and legal requirements, including applicable privacy 
laws.
o
The assent form for a minor used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB before use, and available for 
inspection.
o
The investigator must ensure that the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian is fully informed about the nature and 
objectives of the study and possible risks associated with participation.
o
The source documents must record that the maternal participant was a minor at 
the time of signing the ICD, how the investigator determined that the person 
signing the consent was the maternal participant’s legally acceptable 
representative, the consent signer’s relationship to the maternal participant 
(eg, parent), and that the maternal participant’s assent was obtained.

When the minor maternal participants reach the age of majority during the study, as 
recognized under local law, they must reconsent as adults to remain in the study.

Beginning on 01 April 2022, when the amended civil law in which individuals 18 years 
of age and older are deemed to have reached majority and marriage age for women is 
implemented:
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
The investigator, or a person designated by the investigator, will obtain written informed 
consent from the maternal participant 18 to <20 years of age and married maternal 
participants 16 to <18 years of age.

For all maternal participants <16 years of age and unmarried maternal participants 16 to 
<18 years of age, the investigator, or a person designated by the investigator, will obtain 
written informed consent from the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian as well as the maternal participant’s assent.
10.7.2. Temperature Measurement and Definition of Fever

Axillary temperature will be measured at Visit 1 and as required at an unscheduled visit 
and will be measured by the maternal participants for 7 days following vaccination.

For the maternal participants enrolled in Japan, an axillary temperature of ≥37.5°C
(99.5°F) meets the definition of a current febrile illness in the criteria for temporarily 
delaying vaccine administration described in Section 5.2.3.

For the purpose of recording the temperature in the e-diary, fever is defined as an axillary
temperature of ≥38.0°C (100.4°F) for maternal participants enrolled in Japan.
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants
As Study C3671008 is a first-in-Japanese study and in accordance with a recommendation 
from the Pharmaceuticals and Medical Devices Agency (PMDA), the study will utilize a 
sentinel cohort for the maternal participants enrolled in Japan with progression to study 
enrollment at all study sites after a safety review (data from each maternal participant 
through 14 days after vaccination).  In addition to the study procedures and requirements 
specified in the protocol for Study C3671008, the following procedures will be required for 
the maternal participants enrolled in the sentinel cohort in Japan.
10.7.3.1. Enrollment of Maternal Participants in the Sentinel Cohort
In the sentinel cohort, approximately 8 maternal participants will be enrolled.  No more than 
4 maternal participants per day can be randomized.  Vaccination of the remaining maternal 
participants in the sentinel cohort will commence no sooner than 48 hours after the fourth 
participant received her vaccination.
10.7.3.2. Conclusion of the Sentinel Cohort
After enrollment in the sentinel cohort is completed, the Pfizer internal review committee 
(IRC) will review at least 14 days of postvaccination safety data from all maternal 
participants enrolled in the sentinel cohort, including all local reactions, systemic events, and 
AEs.  An acceptable review will trigger an expansion of study enrollment to all study sites in 
Japan. Refer to the IRC charter for further details.
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10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or Telephone; 14 to 16 Days 
After Vaccination)
All maternal and infant participants enrolled in this study will follow the protocol for 
Study C3671008.  In addition, the maternal participants enrolled in the sentinel cohort in 
Japan will have a Day 15 follow-up visit conducted either at the study site or via telephone.  
This visit should be conducted 14 to 16 days after vaccination.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given since the last visit.

Review the participant’s e-diary data.

Record details of any MA-RTI, including the diagnosis.

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6.

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit.
10.7.3.4. Schedule of Activities for Maternal Participants Enrolled in the Sentinel 
Cohort in Japan
The following table provides an overview of the protocol visits and procedures for the 
maternal participants enrolled in the sentinel cohort in Japan.  Refer to Section 1.2.3.1 for 
the Schedule of Activities for the Maternal Participants: RTI Surveillance for Medically 
Attended Respiratory Tract Illness Visits (Vaccination Until the End-of-Study Visit).
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Visit Description
Screening 
and 
Vaccinationa
Day 15 
Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month 
Postdelivery
Visit Window (Days)
28 Days Prior 
to 
Vaccination 
to Day 1
14 to 16 Days
After 
Vaccination
28 to 42 Days
After 
Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity 
Unit
Clinic, Home, or 
Telephone
Informed consent for maternal 
participant and her infant
X
Assign single maternal participant 
identifier 
X
Demography
X
Medical history including obstetric 
historyd
X
Record current/former alcohol, 
tobacco, marijuana, or any illicit drug 
usage
X
Record vital signs
X
Targeted physical and obstetric 
examination performed on the same 
day or within 7 days before the 
vaccination visit
X
Record details of any antenatal and/or 
postnatal steroid treatment, 
monoclonal antibodies, blood 
products, or Rho(D) immune globulin
X
X
X
X
X
Record details of the maternal 
participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
X
Review eligibility criteria
X
X
X
X
Review temporary delay criteria
X
Prevaccination blood draw for 
serologic assessment (~15 mL) on the 
same day or within 7 days before the 
vaccination visit
Xe
Assign randomization and container 
number
X
E-diary training, dispense digital 
thermometer and measuring devicef
X
Obtain and record baseline 
assessment of prespecified systemic 
events on the day of and prior to 
vaccination in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 
30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic 
assessment 
(~15 mL)
Xe
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Visit Description
Screening 
and 
Vaccinationa
Day 15 
Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month 
Postdelivery
Visit Window (Days)
28 Days Prior 
to 
Vaccination 
to Day 1
14 to 16 Days
After 
Vaccination
28 to 42 Days
After 
Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity 
Unit
Clinic, Home, or 
Telephone
Record pregnancy outcome 
information
X
Review e-diary datag
X
X
Record AEs, as appropriateh
X---------------------------------------------X
Record SAEs, as appropriateh
X
X
X
X
X
Record details pertaining to MA-RTI 
visiti
Assessment of confirmed MA-RTI events during the study as detailed in 
Section 1.2.3.1 of the schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = 
intrapartum antibiotic prophylaxis; ICD = informed consent document; MA-RTI = medically attended 
respiratory tract illness.
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization 
assessments and test results to confirm maternal participant eligibility for this clinical trial can be obtained a
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation 
and collection of AEs and SAEs through 28 days after vaccination must occur even if delivery occurs 
within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge 
following delivery of her infant. Please see Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal 
standard of care, perform an ultrasound examination. As part of the obstetric history, details regarding the 
last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported 
in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital 
thermometer for recording daily temperatures and will be provided with instructions on their use. 
Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) 
a baseline assessment of prespecified systemic events on the day of and prior to vaccination and 
reactogenicity events from Day 1 to Day 7 following vaccination (where Day 1 is the day of vaccination).  
Remind maternal participants that the study staff/field worker may contact them to obtain additional 
information on events entered into the e-diary.  Ask maternal participants to contact the investigator or 
site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 following vaccination, to 
determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal 
participant may be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to 
evaluate maternal participant compliance and as part of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 
28 days after vaccination.  From the signing of the ICD until the maternal participant completes the study, 
all SAEs will be collected.  Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the 
schedule of assessments in Section 1.2.3.1. These events will not be captured as safety events, unless the 
investigator or an appropriate designee deems them to be related to the investigational product or to have 
resulted in death.
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10.7.4. Exclusion Criterion 12 Clarification
For exclusion criterion 12, “Current alcohol abuse or illicit drug use. Note: Marijuana use is 
not considered an exclusion criterion for the study when elicited in participant screening, 
though it may be considered illicit in some locales.” In Section 5.2.1, any current use of an 
illicit drug including marijuana will not be permitted for maternal participants enrolling from 
study sites in Japan.
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and Unanticipated SAE
Caused by Medical Device
Definition of SAE caused by medical device:
An SAE caused by medical device is defined as an AE caused by a medical device which led 
to an outcome characteristic to SAEs, or a device-related incident whose recurrence might 
lead to death or serious deterioration in health.
NOTE: See the Medical Device Adverse Events, Adverse Device Effects, Serious Adverse 
Events, and Device Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting section (Appendix 4). Deficiencies fulfilling the definition of an 
AE/SAE will also follow the processes outlined in Section 8.3.3 and Appendix 2 of the 
protocol.
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix – Applicable 
to the Philippines, Gambia, and South Africa Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Participants who have not had ultrasound assessments to determine eligibility during 
routine care should be consented and have an ultrasound within 90 days prior to 
vaccination in order to comply with inclusion criteria #1 in Section 5.1.1.
Safety endpoints:
The time period and frequency for collecting AE and SAE information by the investigator 
and site staff should follow Appendix 2, with the exception of the additional screening 
window for sites conducting ultrasounds procedures from -90 to -28 days. At these sites, the 
safety reporting periods should be as follows:

AEs occurring up to 48 hours after ultrasound assessment that the investigator deems are 
related to the study procedure must be reported in the CRF.

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

The active collection period for nonserious AEs begins 28 days prior to vaccination and 
continues through a minimum of 28 calendar days after vaccination as described in
Section 8.3.1 and Section 10.2.
MA-RTI endpoints:
Maternal MA-RTIs are collected from the time of vaccination to the end of the study period 
as described in Section 8.1.2.
Note: For maternal participants who are screen failures, the active collection period ends 
when screen failure status is determined.
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10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to South 
Korea and Taiwan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Section 5.1.1: Inclusion criterion 1 states that healthy women ≤49 years of age who are 
between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an 
uncomplicated, singleton pregnancy, who are at no known increased risk for complications 
are eligible for the study.
Please find below country-specific minimum age requirements for study entry into the 
protocol:

In South Korea, the minimum age requirement of maternal participants who can be 
enrolled into the study is ≥19 years of age.

In Taiwan, the minimum age requirement of maternal participants who can be enrolled 
into the study is ≥20 years of age.
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10.10. Appendix 10: Country-Specific Appendix – Applicable to South Korea Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Exclusion Criterion 12 Clarification
For exclusion criterion 12, “Current alcohol abuse or illicit drug use.  Note: Marijuana use is 
not considered an exclusion criterion for the study when elicited in participant screening, 
though it may be considered illicit in some locales.”  In Section 5.2.1, any current use of an 
illicit drug, including marijuana, will not be permitted for maternal participants enrolling 
from study sites in South Korea.
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10.11. Appendix 11: Country-Specific Appendix – Applicable to the Philippines Only
The following supplementary text should be read in conjunction with the C3671008 protocol
Section 10.1, Appendix 1 requirements, which details the Regulatory, Ethical, and Study 
Oversight Considerations, including the compensation/reimbursement requirements for study 
participants.
Study participants enrolled in the Philippines may be compensated to cover expenses related 
to completion of maternal and infant study visits in accordance with country-specific
applicable laws and regulations, as approved by the IRB/EC. In addition, compensation may 
be provided upon e-diary completion with the approval of the IRB/EC.
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10.12. Appendix 12: Country-Specific Appendix – Applicable to New Zealand Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Currently, the protocol states that a full date of birth will be collected, for both maternal and 
infant participants in the study as per Section 8.10.1, bullet 3, and Section 8.11.1, bullet 5,
respectively. To address the HDEC’s recommendation pertaining to the collection and 
overseas transfer of identifiable participant data, specifically the date of birth, to the Sponsor, 
the following modifications have been made to the respective bullets concerning the date of 
birth collection in the study in accordance with country-specific applicable laws and 
regulations:
Revised text for Section 8.10.1, bullet 3 (Maternal Participants)
Obtain and record the participant demography (including the true year of birth only
[01-JAN-YYYY], sex, race, racial designation, and ethnicity). The year of birth will be 
collected to critically evaluate the immune response and safety profile by age
Revised text for Section 8.11.1, bullet 5 (Infant Participants)
Obtain and record the participant demography (including the complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity). The date of birth will be 
collected to critically address efficacy analyses and evaluate the immune response and 
safety profile by age.
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10.13. Appendix 13: Protocol Document History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the table of contents (TOC). The protocol amendment summary of changes
tables for past amendments can be found below:
Document History
Document
Version Date
Summary of Changes and Rationale
Original 
protocol
05 December 2019
N/A
Protocol 
amendment 1
24 March 2020
PROTOCOL SUMMARY: Clarification text was 
added in various sections of the main body of the 
protocol to match the revisions made to the protocol 
summary.
Throughout: The protocol now contains final 
wording regarding the double-blinded, 
placebo-controlled study design and the final dose 
and formulation of RSVpreF. This is as a result of 
the analysis of the safety, tolerability, and 
immunogenicity data from the C3671003 maternal 
Phase 2b trial.
Section 1.2.1 Study Design – Maternal Participants: 
The final dose and formulation of RSVpreF were 
inserted, including the lyophile match for the 
placebo.
Section 1.2.2 Study Design – Infant Participants: The 
text box pertaining to the vaccine group arms was 
deleted. The maternal-infant dyads will be randomly 
assigned in this study. Rationale: Infant participants 
will not be administered the investigational product. 
Therefore, the current placement is potentially 
confusing to readers.
Section 1.2.3 Schedule of Activities for Maternal 
Participants, Section 5.2.3, and Section 8.10.1: 
Clarification text was added as follows:
o
The immunogenicity blood collection and 
physical examination window requirements 
before vaccination were aligned to provide 
greater logistical convenience for the 
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Document
Version Date
Summary of Changes and Rationale
investigational sites with respect to enrolling 
participants into the study.
o
The wording for the study objectives pertaining 
to the request for IAP details for maternal 
participants with a GBS status was revised to be 
consistent with the study procedural objectives, 
which are to collect GBS status and to ascertain 
whether any medication was given for IAP. This 
resulted in the deletion of the text in Section 
6.5.3, as this information is captured in Section 
8.10.3.
o
A reference to the immunogenicity blood draws 
for maternal participants was added to clarify the 
AE reporting requirements for events that might 
occur as a result of study-related procedures.
Section 1.2.3.1 Schedule of Activities for Maternal 
Participants – Respiratory Tract Illness (RTI) 
Surveillance for Medically Attended Respiratory 
Tract Illness (MA-RTI) Visits:
o
Details to be collected during an MA-RTI were 
revised.
o
Clarification was added regarding the safety 
reporting requirements for MA-RTI events that 
might occur during the study.
Section 1.2.4 Schedule of Activities for Infant 
Participants:
o
Visit flexibility was increased to prioritize 
participant safety and adherence to local 
guidance in the event of a COVID-19 outbreak or 
other outbreaks.
o
The physical examination and vital sign 
assessment windows for the study were aligned 
to provide greater logistical convenience for the 
investigational sites with respect to compliance to 
study protocol requirements.
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Document
Version Date
Summary of Changes and Rationale
o
The protocol safety reporting criteria and period 
for AEs, SAEs, and NDCMCs were streamlined.
Section 1.2.4.1 Schedule of Activities for Infant 
Participants: RTI Study Visits During the Study: The 
table was revised, including splitting the schedules of 
activities for unscheduled RTI visits for all infant 
participants into RTI surveillance from birth to 
6 months and RTI surveillance from 6 months to the 
end of the study. The procedures were streamlined 
for these RTI study visits to improve clarity and 
consistency.
Table 1: Clarification has been added as to when a 
study visit is triggered for reported MA-RTI endpoint 
events on the study. Day 1 is the day of the MA-RTI
visit as detailed in Section 8.11.7.
In addition, clarification has been added as to what 
constitutes the site source for confirmed study 
endpoint criteria, in order to provide the sites 
guidance on what documentation will eventually be 
submitted to the EAC for evaluation.
Section 3.1: The exploratory endpoints were revised 
to correspond with the planned statistical analyses of 
RTI events in the pediatric population. This does not 
represent a change to the study design but instead 
better reflects the total statistical analysis plan.
Section 3.1, Section 3.2, and throughout: To improve 
clarity and ensure consistency, the use of 
“RSV-neutralizing antibody titers” has been changed 
to RSV serum neutralizing titers.” This is the 
sponsor’s preference based on what the neutralizing 
activity assay is based upon, and in this case, it is 
whole serum and not just the purified antibodies 
during these immunogenicity assessments.
Section 3.3, Section 8.1.1.2, Section 8.1.3, and 
Section 10.2: For further clarification, the protocol’s 
safety and endpoint reporting requirements were 
amended to ensure consistency with Pfizer’s updated 
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safety reporting requirements for endpoint-defined 
studies.
Section 4.3: The text “availability of these data are 
expected in 2020” was removed as this statement 
does not accurately reflect the current 
decision-making process for the dose and 
formulation selection activities for this study.
Section 5.2.1: Clarification text was added to the 
exclusion criterion for BMI and congenital anomalies 
based on study requirements.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: The 
Tdap administration requirements text was modified 
to describe the timing of vaccinations based on data 
from the C3671004 study, once available. This 
change will better reflect clinical practice and will 
facilitate recruitment of suitable maternal participants 
for the study.
Section 6.1.1, Section 6.1.3, Section 8.4, and 
Section 8.10.1: Clarification text was added to 
address investigational product reconstitution volume 
and administration requirements. This change is to 
ensure consistency with the investigational product 
administration documentation for the study.
Section 7.2: Clarification text was added to address 
the notification process for biological sample 
management in the event of study participant 
withdrawal from the study.
Section 7.3 and Appendix 1 Informed Consent 
Process: Clarification text was added to address 
study retention and data collection requirements for 
the study. In addition, further clarification has been 
added to emphasize the informed consent process 
during circumstances where the maternal participant 
is no longer able to provide consent but the infant 
participant’s continued participation in the study 
could be retained by the parent(s)/legal guardian as 
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per local regulatory, local laws, and local governance 
approval.
Section 8.1.1.1: Clarification text was added to 
provide guidance regarding the midturbinate swab 
processing requirements and the definition of 
acceptable certified/accredited laboratory bodies for 
this process in the study.
Section 8.2.1.1 and Section 8.10.1: The reporting 
requirements for Grade 4 local reactions in the study 
were clarified; the assessment and reporting are 
carried out by the investigators (or appropriately 
qualified designees).
Section 8.3.1.1, Section 8.3.1.2, Section 8.3.5.1, 
Section 8.3.5.2, Section 8.10, and Section 8.11: The 
reporting requirements were clarified for this 
vulnerable patient population with regard to AEs and 
SAEs likely to occur in the study in women with GA 
eligibility criterion between 24 0/7 and 36 0/7 weeks.
Section 8.3.6: Text was added to address and 
standardize reporting procedures for AESIs for this 
patient population.
Section 8.3.7 and Appendix 4: Several Pfizer text 
revisions were incorporated regarding device 
deficiencies and the safety reporting requirements for 
this study.
Section 8.10: The immunogenicity blood collection 
and physical examination window requirements 
before vaccination were aligned to provide greater 
logistical convenience for the investigational sites 
with respect to enrolling participants into the study.
Section 8.10.1: The prepregnancy BMI text revisions 
in Section 5.2.1 were aligned with the study 
assessment requirements for maternal participants at 
screening.
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Version Date
Summary of Changes and Rationale
Section 8.10.2, Section 8.10.3, Section 8.10.4, and 
Section 8.10.6: Clarification text was added to the 
MA-RTI reporting requirements for maternal 
participants in the study to provide guidance and 
ensure the investigational sites provide accurate 
information pertaining to these self-reported events.
Section 8.11.1 to Section 8.11.6: Clarification text 
was added (where applicable) to address the 
following study assessments:
o
“Birth weight must be the first birth weight and 
cannot be based on the standard-of-care 
examination” was removed as this statement is 
confusing to the investigational sites. Birth 
weight assessments have now been realigned 
with standard-of-care assessments at the study 
visit to aid compliance with study assessments 
and requirements.
o
Clarification text was added regarding the 
reporting of standard-of-care measurements for 
vital sign assessments.
o
In addition, the physical examination and vital 
sign assessment windows for the study were 
aligned to provide greater logistical convenience 
for the investigational sites to comply with study 
protocol requirements.
o
For further clarification, the RTI study visit 
assessment requirements were amended to 
emphasize the difference between the MA-RTI 
visit criteria and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements.
Section 8.11.7.1: For further clarification, the RTI 
study visit assessment requirements have been 
amended to emphasize the following:
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o
The RTI study visit window, including nasal 
swab collection from the MA-RTI notification 
for the infant participant.
o
Duplicate text was removed pertaining to the 
MA-RTI definition and the signs and symptoms 
of interest pertinent to an RTI study visit.
o
Guidance regarding the difference between the 
MA-RTI visit and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements.
Section 8.11.8: Clarification text was added to 
address the RTI study visit window, including nasal 
swab collection from the MA-RTI notification for the 
infant participant.
o
For further clarification, the RTI study visit 
assessment requirements have been amended to 
emphasize the difference between the MA-RTI 
visit and the subsequent study visit after the event 
has been reported. This is to improve clarity and 
consistency with the RTI study visit requirements 
and provide guidance to the investigational sites.
Section 9.1.2.1, Section 9.1.2.2, Section 9.4.1, 
Section 9.2, and Section 9.5: Text was added to 
clarify the statistical analysis procedures in line with 
the current revisions.
Appendix 2: Clarification text was added to support 
the safety and pregnancy outcome reporting 
requirements for participants who may experience 
exposure during pregnancy while in the study.
Appendix 5: Further clarification was added to the 
background factors of interest during the infant’s 
participation in the study.
Appendix 6: Clarification text was added to the 
examination and treatment criteria checklist for 
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reported MA-RTI visits. This is to ensure there is 
some consistency to the source records provided for 
these events in relation to the protocol requirements.
Throughout: Several changes were made to 
incorporate the replacement of the Clinical Trial 
Serious Adverse Event Report Form (CT SAE 
Report Form) to Vaccine SAE Reporting Form, as 
part of the new vaccine SAE reporting requirements 
for Pfizer.
Throughout: Minor editorial revisions were 
incorporated as appropriate.
Protocol 
amendment 2
26 June 2020
Section 5.1.1: Administrative update was 
incorporated to address the recently added 
Appendices 7 and 8.
Appendix 7: A country-specific appendix was added 
for Japan to address consent/assent issues for minors, 
temperature measurement, definition of fever, and 
enrollment of maternal participants in the sentinel 
cohort for safety monitoring.
Appendix 8: A country-specific appendix was added 
for the Gambia and South Africa to address an 
extension to the screening period for maternal 
participants with regard to GA requirements and 
consent process.
Protocol 
amendment 3
26 August 2020
PROTOCOL SUMMARY: Added clarification text 
to the exploratory endpoint section for the infant 
participants; changes were made in the protocol 
summary to match the revisions made in the main 
body of the protocol.
Section 1.2.2: Study Design – Infant Participants: 
Added text to address RSV seasonality and the 
required RTI surveillance periods during the study. 
Rationale: The previous placement was potentially 
confusing to readers. The revisions provide clarity to 
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the investigational sites with regard to the RTI 
surveillance follow-up activities.
Section 1.2.3 and Section 1.2.3.1: Added clarification 
text (where applicable) to address the following:
o
Added “Home or Telephone” to the type of visit 
options allowed for the 6-month-postdelivery 
visit.
o
Added clarification text to the alcohol history 
reporting requirements and included “obstetric” 
in the screening assessment requirements for the 
study.
o
Added “study staff,” as study personnel are 
allowed to collect and report baseline and 
reactogenicity assessments reported during the 
evaluation period.
o
Added clarification text regarding the reporting 
requirements for AEs, SAEs, and MA-RTIs for 
maternal participants.
Section 1.2.4 - Schedule of Activities for Infant 
Participants:
o
Added “Home” to the type of visit options 
allowed for the 1-month and 6-month follow-up 
visits and added further clarification to the visit 
status during potential COVID-19 pandemic 
situations or other natural disasters. Rationale: 
Infant participant visit options were aligned with 
the maternal participant requirements to allow for 
visit flexibility.
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o
For further clarification, the physical examination 
and vital sign assessment expectations at birth 
and at the 1-month visit were aligned to provide 
greater logistical convenience for the 
investigational sites to comply with study 
protocol requirements.
Sections 1.2.4, 1.2.4.1, 8.1.1, and 8.11 to 8.12: 
Added clarification text (where applicable).
o
To address alternate nasal swab collection 
procedures, if needed, during potential 
COVID-19 pandemic situations or other natural 
disasters.
o
Clarification text was added with regards to the 
start of the reporting period for MA-RTI events 
upon the infant’s delivery. This is to improve 
clarity and consistency with the capturing and 
reporting requirements for MA-RTI events and 
provide guidance to the investigational sites.
Sections 1.2.4.1, 8.11.7.1, 8.11.8, and Appendix 6:
o
Added temperature and body weight 
measurements for infant participants during study 
RTI visits.
o
For vital sign measurements, especially oxygen 
saturation measurements (where applicable), 
clarification text was added to state that it is 
recommended that the participant not be 
receiving supplemental oxygen at the time of 
measurement.
These updates are to ensure consistency with the 
study RTI assessment visits after a confirmed 
MA-RTI event.
Section 3.1: Added clarification text as follows:
o
Table 1.  Primary and Secondary Endpoint 
Events and Definitions in Infant Participants: For 
further clarification, added descriptive text to the 
table header to address endpoint events listed 
within the table. In addition, made corrections to 
the overlapping respiratory rate measurements 
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provided for some study endpoint events. These 
changes were made to improve clarity and 
consistency with the endpoint reporting and 
evaluation process for the study.
o
For the infant participant exploratory objectives, 
added the planned statistical analysis period of 
“after 6 months of age” to “all-cause MA-RTIs 
and hospitalizations due to RSV” in the pediatric 
population based on regulatory authority 
feedback from South Korea.
o
Incorporated revisions to align endpoints with 
study duration, specifically MA-LRTIs due to 
RSV A and RSV B, and MA-RTIs associated 
with non-RSV respiratory pathogens.
o
Added clarification text to address the analysis 
plans for the healthcare utilization endpoints.
Section 4.1: For further clarification, added text to 
address the desire to enroll across gestational age.
Section 4.3: Added a brief summary of the safety and 
immunogenicity results from the C3671003 trial to 
support the decision-making process for this study.
Section 5.1.1: Inserted administrative 
update/clarification text with regards to:
o
Participant eligibility guidance documentation 
available within the investigator site file.
o
The informed consent process for maternal 
participants.
Section 5.2.1: Based on study requirements:

Added clarification text to exclusion criterion 7, 
which addresses the investigator’s judgment 
when assessing participant eligibility (maternal 
participant or her fetus) and regional endemic 
conditions during routine maternal care, as per 
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local standards of care and obstetric 
recommendations.

Added clarification text to address illicit drug use 
pertaining to marijuana.
Section 5.2.2: Deleted the infant participants 
exclusionary criterion pertaining to the “receipt of 
investigational or approved monoclonal antibodies 
against RSV.” This was to provide additional 
clarification to the investigational sites with regards 
to the infant’s eligibility criteria.
Sections 5.2.3, 6.5.1, and 6.5.2: Modified the Tdap 
administration requirements text to describe the 
timing of vaccinations based on recent data from the 
C3671004 study (A Phase 2b, Placebo-Controlled, 
Randomized, Observer-Blind Study to Evaluate the 
Safety, Tolerability, and Immunogenicity of a 
Respiratory Syncytial Virus [RSV] Vaccine When 
Administered Concomitantly With Tetanus, 
Diphtheria, and Acellular Pertussis Vaccine [Tdap]
in Healthy Nonpregnant Women 18 Through 
49 Years of Age; ClinicalTrials.gov ID: 
NCT04071158).
Section 6.1.4: Added text to clarify what constitutes 
a medical device with regards to the investigational 
product in this study.
Section 6.5.2: Added text to clarify the tetanus and 
diphtheria vaccine administration requirements 
during the study.
Section 6.5.4: For further clarification, added text to 
address prohibited vaccinations and treatments for 
infant participants. This is to provide guidance to the 
investigational sites.
Section 6.5.5: Added text to clarify the permitted 
treatments, vaccines, and procedures acceptable to 
infant participants enrolled in the study.
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Sections 8.2.1 to 8.2.1.2 and Section 8.10.1: For 
further clarification, amended the e-diary completion 
requirements to emphasize the different reporting 
and/recording options for reactogenicity events 
should illiterate maternal participants be enrolled in 
the study. This is to improve clarity and consistency 
with the reactogenicity reporting requirements at the 
investigational sites.
Table 6 and Section 8.2.1.3: Based on regulatory 
feedback, provided a description of the intensity 
scale for the reactogenicity event “fever.”
Sections 8.3.1 to 8.3.1.2, Sections 8.3.5.2 to 8.3.8.1, 
and Section 10.2.3: Added clarification text (where 
applicable) to address the following safety-related 
updates and provide guidance to the investigational 
sites:
o
Several Pfizer text revisions were incorporated 
regarding the safety reporting requirements for 
this study.
o
Text was added to clarify the SAE reporting 
timelines for the study and provide guidance 
regarding the evaluation of and assessment 
procedures for congenital anomalies.
Section 8.10.1: For further clarification, aligned the 
study assessment window requirements before 
vaccination to provide guidance and greater logistical 
convenience for the investigational sites with respect 
to enrolling participants into the study.
Section 8.10.3: Added clarification text with regards 
to the reporting requirements for maternal 
participants diagnosed as GBS positive and 
pregnancy outcome information. This is to improve 
clarity and consistency with the reporting 
requirements at investigational sites.
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Section 8.11.1: Added clarification text on how the 
infant participant’s identifier will be assigned for this 
study.
Sections 8.11.1 to 8.11.6: Added clarification 
regarding the reporting of standard-of-care 
measurements for vital sign assessments, 
measurements, and physical examination procedures 
(where applicable) to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 9.2 and Section 9.4.1: Modified text to more 
generally describe Type 1 error control procedures 
and refer to the SAP for details.
Section 9.4.3.2: Added clarification regarding the 
planned analyses for the healthcare utilization 
endpoints.
Section 10.2.5: Deleted the “SAE Reporting to Pfizer 
Safety via an Electronic Data Collection Tool” 
section. For consistency, only the Vaccine SAE 
Reporting Form process will be used.
Appendix 6: Added clarification text to the 
microbiological data collection requirements for the 
study based on any pathogen-related 
assessments/findings performed as part of the 
participant’s routine clinical care.  This is to ensure 
there is some consistency to the source records 
provided for these events in relation to the protocol 
requirements and to address regulatory guidance in 
light of the COVID-19 outbreak or other outbreaks.
Appendix 7: Added clarification text to the 
following:
o
Incorporated minor editorial revisions into the 
Schedule of Activities for Maternal Participants 
Enrolled in the Sentinel Cohort in Japan.
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o
Added clarification text to exclusion criterion 12 
regarding the definition of illicit drug use based 
on country-specific requirements.
o
Incorporated clarification text regarding the 
definition of an SAE caused by a medical device.
Appendix 9: Added a country-specific appendix for 
South Korea and Taiwan to address the minimum 
age requirements for maternal participants in each 
country.
Throughout: Incorporated minor editorial revisions 
as appropriate.
Protocol 
amendment 4
22 March 2021
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made in 
the main body of the protocol.
Section 1.2.3: Added text to address safety reporting 
requirements during consent/assent for minors 
enrolled as maternal participants in the study.
Section 2.1: Added text to address the enrollment of 
adolescent menarchal females into the study, ie, no 
lower age limit for maternal participants.  This is 
based on recent regulatory feedback regarding the 
study design for RSVpreF evaluation in pregnant 
adolescent females.
Section 3.1 and Section 9.4.1: The secondary and 
exploratory endpoints were revised to correspond 
with the planned statistical analyses of RTI events in 
the pediatric population:
o
Updated secondary objectives pertaining to 
hospitalization and MA-LRTI due to any cause, 
extended the efficacy analysis to be in line with 
the duration of follow-up for infant participants 
during the first year of their participation in the 
study, which is 360 days after birth.
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o
An additional secondary objective added to 
assess the efficacy of RSVpreF in reducing the 
incidence of MA-LRTI due to RSV.
o
An additional exploratory objective added to 
assess the efficacy of RSVpreF in reducing the 
incidence of MA-RTI, MA-LRTI, and severe 
MA-LRTI in premature infants 37 weeks of 
age.
These updates are reflected in the statistical section 
of the protocol and do not represent a change to the 
study design but instead better reflect the total 
statistical analysis plan.
Section 4.1: For further clarification, added text to 
address the consent/assent requirements for minors 
enrolled as maternal participants in the study.
Section 4.1 and Section 4.1.2: Given the COVID-19 
pandemic situation, and the variable RSV season, the 
maternal participant sample size on the study may 
need to be increased and enrollment could possibly 
go up to 10,000 maternal participants.
Section 4.4: Added text to clarify the study definition 
for a completed maternal/infant participant in the 
study.
Section 5.1.1: Added clarification with regards to 
inclusion criteria and incorporated administrative 
update:
o
Removed the lower age limit for healthy pregnant 
females likely to be eligible for enrollment in the 
study.  This change will facilitate recruitment of 
suitable maternal participants for the study.
o
Allowed the GA determination to be based upon 
the first trimester ultrasound examination alone, 
without the last menstrual period, in countries 
where this is routine.  This is to improve clarity 
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and consistency with the GA determination 
requirements at the investigational sites.
o
Updated criterion 4 regarding fetal anomaly 
ultrasound examination requirements in the 
study.  This is to improve clarity and ensure 
consistency with study requirements at 
investigational sites.
Section 5.2.1: Incorporated administrative update and 
clarification with regards to:
o
Marijuana use and maternal participant eligibility 
in the study.
o
The use of licensed COVID-19 vaccines or 
COVID-19 vaccines authorized for temporary, or 
emergency use based on regulatory and national 
recommendations in maternal participants 
enrolled into the study.
This was to provide additional clarification to the 
investigational sites with regards to the eligibility 
criteria of maternal participants.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: Due 
to the current COVID-19 pandemic, added text to 
clarify the vaccination delay criteria and nonvaccine 
administration window for maternal participants 
receiving licensed COVID-19 vaccines or 
COVID-19 vaccines authorized for temporary or 
emergency use.  This change is consistent with other 
nonstudy vaccines allowed in the study.
Section 6.3.1, Section 8.1.2, Section 8.2.1 to 
Section 8.2.1.3, Section 8.3, Section 8.3.1, 
Section 8.3.1.2, Section 8.10.1 to Section 8.10.6, 
and Section 10.1.3: Added text to clarify the 
consent/assent requirements during study 
procedures/assessments in the event “a minor” is 
enrolled as a maternal participant.  This is to improve 
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clarity and ensure consistency for the investigational 
sites to comply with study protocol requirements.
Section 8.3.8.1: Added text to make the following 
safety-related updates and provide guidance to the 
investigational sites:
o
Incorporated safety reporting text for participants 
who report a positive test result for SARS-CoV-2 
during the study.
o
Text was added to clarify the AESI reporting 
requirements for the study and provide guidance 
regarding the definition of and categorization of 
a developmental delay in infant participants.
Section 8.10.1: Incorporated administrative update 
regarding which body systems are deemed 
mandatory and which discretionary during physical 
examination procedures for maternal participants in 
the study.  This is to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 8.11.1: Incorporated text regarding the 
reporting of standard-of-care measurements for vital 
sign and physical examination procedures at the 
infant’s birth.  This is to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 8.11.7, Section 8.11.8, and Section 8.12: 
Added text to clarify the nasal swab collection 
requirements from infant participants during a 
confirmed MA-RTI episode.  This is to provide 
flexibility and prioritize participant safety during 
the study.
Section 9.3, Section 9.4.2, Section 9.4.3, and 
Section 9.4.3.2: Added text to clarify the statistical 
analysis procedures in line with the current revisions.
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Appendix 7 and Appendix 9: Removed the lower 
age limit for healthy pregnant females likely to be 
eligible for enrollment into the study.  In addition, 
incorporated minor editorial revisions to the 
informed consent document for maternal participants 
enrolled in Japan only.
Appendix 8: Added the Philippines to the list of 
countries impacted by an extension to the screening 
period for maternal participants with regard to GA 
requirements and consent process.
Throughout: Incorporated minor editorial revisions 
as appropriate.
Protocol 
amendment 5
12 January 2022
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made in 
the main body of the protocol.
Section 1.1 and Section 3.1: Typographical error 
with the third secondary efficacy endpoint pertaining 
to EAC activities was removed to align with the 
protocol-defined procedures and SAP.
Section 5.2.3: Administrative update to clarify the 
coadministration window requirements for licensed 
COVID-19 vaccines and COVID-19 vaccines 
authorized for temporary or emergency use, based 
on evolving regulatory and national guidelines.
Section 6.5.1 and Section 6.5.2: Added text to clarify 
the coadministration requirements for any licensed 
vaccines containing pertussis in maternal participants 
likely to be eligible for the study.
Section 1.1, Section 4.1, Section 9.2, Section 9.4.1, 
and Section 9.5: Modified text to address additional 
interim analyses planned for the study.
Appendix 10: Added a country-specific appendix for 
South Korea to address marijuana use and maternal 
participant eligibility in the study.
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Appendix 11: Added a country-specific appendix for 
The Philippines at the request of the Philippine 
Health Research Ethics Board (PHREB) that clarifies 
the compensation/reimbursement requirements for 
participants enrolled in the Philippines based on 
national regulatory laws and recommendations.
Protocol 
amendment 6
01 June 2022
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made 
in the main body of the protocol.
Section 1.2.4: Updated the window of assessment for 
infant physical examination from 48 to 72 hours to 
reflect the current entry in Section 8.11.1.
Section 1.2.4.1: Revisions were made to the schedule 
of activities for infant participants to clarify language 
related to RTI assessments.
Section 2.2, Section 4.1, and Section 4.1.2: Modified 
language to justify a new enrollment strategy and 
endpoint case-accrual plan.
Section 5.2.1: Added text to exclusion criterion 11 to 
clarify that maternal participants who have 
previously received SARS-CoV-2 monoclonal 
antibodies as part of their COVID-19 treatment, 
postexposure prophylaxis, or preexposure 
prophylaxis are now permitted to be enrolled in the 
study.
Section 9.2, Section 9.4.1, and Section 9.5: Modified 
text to address final analyses planned for the study.
Section 10.1.5: Several Pfizer protocol template text 
revisions were incorporated pertaining to the 
dissemination of clinical study data.
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10.14. Appendix 14: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ADE
adverse device effect
AESI
adverse event of special interest
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
Apgar
appearance, pulse, grimace, activity, and respiration
AST
aspartate aminotransferase
BMI
body mass index
CBER
Center for Biologics Evaluation and Research
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
Clinical Laboratory Improvement Amendments
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EAC
endpoint adjudication committee
EACC
endpoint adjudication committee charter
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
E-DMC
external data monitoring committee
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine
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Abbreviation
Term
GA
gestational age
GBS
group B streptococcal
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBIG
hepatitis B immune globulin
HBV
hepatitis B virus
HCP
healthcare provider
HDEC
Health and Disabilities Ethics Committee
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HPV
human papillomavirus
IAP
intrapartum antibiotic prophylaxis
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
Ig
immunoglobulin
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ISF
investigator site file
ISO
International Organization for Standardization
IUI
intrauterine insemination
IV
intravenous
IWR
interactive Web-based response
LFT
liver function test
LMIC
lower- and middle-income country
LMP
last menstrual period
LRTI
lower respiratory tract illness
MA-LRTI
medically attended lower respiratory tract illness
MA-RTI
medically attended respiratory tract illness
MCAR
missing completely at random
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
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Abbreviation
Term
NAAT
nucleic acid amplification technology
NDCMC
newly diagnosed chronic medical condition
PACL
protocol administrative change letter
PCD
primary completion date
PCR
polymerase chain reaction
PFS
prefilled syringe
PHREB
Philippine Health Research Ethics Board
PMDA
Pharmaceuticals and Medical Devices Agency
PT
prothrombin time
RAD
reactive airway disease
RCDC
reverse cumulative distribution curve
RSV
respiratory syncytial virus
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RTI
respiratory tract illness
RT-PCR
reverse transcription–polymerase chain reaction
SAE
serious adverse event
SADE
serious adverse device effect
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SMS
short message service
SoA
schedule of activities
SOP
standard operating procedure
SpO2
oxygen saturation
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Tdap
tetanus, diphtheria, and acellular pertussis vaccine
TOC
table of contents
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VE
vaccine efficacy
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11. REFERENCES
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Elsevier; 2018:1162-5.
2
Hall CB, Weinberg GA, Blumkin AK, et al. Respiratory syncytial virus–associated 
hospitalizations among children less than 24 months of age. Pediatrics.
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3
Shi T, McAllister DA, O’Brien KL, et al. Global, regional, and national disease burden 
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Scheltema NM, Gentile A, Lucion F, et al. Global respiratory syncytial virus-associated 
mortality in young children (RSV GOLD): a retrospective case series. Lancet Glob
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5
Parikh RC, McLaurin KK, Margulis AV, et al. Chronologic age at hospitalization for 
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6
American Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis 
Guidelines Committee. Policy statement—updated guidance for palivizumab 
prophylaxis among infants and young children at increased risk of hospitalization for 
respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-20.
7
Blanken MO, Rovers MM, Molenaar JM, et al. Respiratory syncytial virus and recurrent 
wheeze in healthy preterm infants. N Engl J Med. 2013;368(19):1791-9.
8
Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk 
of wheeze and allergy by age 13 years. Lancet. 1999;354(9178):541-5.
9
Weber MW, Mulholland EK, Greenwood BM. Respiratory syncytial virus infection in 
tropical and developing countries. Trop Med Int Health. 1998;3(4):268-80.
10
Glezen WP, Taber LH, Frank AL, et al. Risk of primary infection and reinfection with 
respiratory syncytial virus. Am J Dis Child. 1986;140(6):543-6.
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American Academy of Pediatrics. Respiratory syncytial virus. In: Kimberlin DW, Brady 
MT, Jackson MA, Long SS, eds. Red book: 2018 report of the Committee on Infectious 
Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:682-92.
12
Prescott WA Jr, Doloresco F, Brown J, et al. Cost effectiveness of respiratory syncytial 
virus prophylaxis: a critical and systematic review. Pharmacoeconomics.
2010;28(4):279-93.
13
Synagis [prescribing information]. Gaithersburg, MD: MedImmune LLC; 2017.
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14
Munoz FM, Ralston SL, Meissner HC. RSV recommendations unchanged after review 
of new data. AAP News. Available from: 
http://www.aappublications.org/news/2017/10/19/RSV101917. Published: 19 Oct 2017. 
Accessed: 15 Nov 2018.
15
The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus 
monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection 
in high-risk infants. Pediatrics. 1998;102(3):531-7.
16
Baker CJ, Carey VJ, Rench MA, et al. Maternal antibody at delivery protects neonates 
from early onset group B streptococcal disease. J Infect Dis. 2014;209(5):781-8.
17
Dangor Z, Kwatra G, Izu A, et al. Correlates of protection of serotype-specific capsular 
antibody and invasive group B Streptococcus disease in South African infants. Vaccine.
2015;33(48):6793-9.
18
Scuff TH, Blain AE, Watt J, et al. Impact of the US maternal tetanus, diphtheria, and 
acellular pertussis vaccination program on preventing pertussis in infants <2 months of 
age: A case-control evaluation. Clin Infect Dis. 2017;65(12):1977-83.
19
Baxter R, Bartlett J, Fireman B, et al. Effectiveness of vaccination during pregnancy to 
prevent infant pertussis. Pediátrica. 2017;139(5):e20164091.
20
Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and 
protection of their infants. N Engl J Med. 2014;371(10):918-31.
21
Benowitz I, Esposito DB, Gracey KD, et al. Influenza vaccine given to pregnant women 
reduces hospitalization due to influenza in their infants. Clin Infect Dis.
2010;51(12):1355-61.
22
Forbes ML, Kumar VR, Yogev R, et al. Serum palivizumab level is associated with 
decreased severity of respiratory syncytial virus disease in high-risk infants. Hum 
Vaccin Immunother. 2014;10(10):2789-94.
23
Schmoele-Thoma B, Falsey AR, Walsh EE, et al. Phase 1/2, first-in-human study of the 
safety, tolerability, and immunogenicity of an RSV prefusion F-based subunit vaccine 
candidate [poster 2755]. Poster presented at IDWeek; 02-06 Oct 2019; Washington, DC.
24
Pichichero ME, Rennels MB, Edwards KM, et al. Combined tetanus, diphtheria, and 
5-component pertussis vaccine for use in adolescents and adults. JAMA.
2005;293(24):3003-11.
25
Block SL, Nolan T, Sattler C, et al. Comparison of the immunogenicity and 
reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 
18) L1 virus-like particle vaccine in male and female adolescents and young adult 
women. J Pediatr. 2006;118(5):2135-45.
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26
European Medicines Agency. Scientific discussion. Gardasil. In: European Public 
Assessment Report (EPAR). London, England: European Medicines Agency; 2006.
27
Straňák Z, Saliba E, Kosma P, et al. (2016) Predictors of RSV LRTI hospitalization in 
infants born at 33 to 35 weeks gestational age: a large multinational study (PONI). PLoS 
One. 2016;11(6):e0157446.
28
Gilbert W, Jandial D, Field N, et al. Birth outcomes in teenage pregnancies. J Matern 
Fetal Neonatal Med. 2004;16(5):265-70.
29
McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer 
bound to a prefusion-specific neutralizing antibody. Science. 2013;340(6136):1113-7.
30
Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants 
despite prior administration of antigenic inactivated vaccine. Am J Epidemiol.
1969;89(4):422-34.
31
Graham BS. Biological challenges and technological opportunities for respiratory 
syncytial virus vaccine development. Immunol Rev. 2011;239(1):149-66.
32
Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial 
virus purified fusion protein-2 vaccine in pregnant women. Vaccine. 2003;21(24):3465-
7.
33
Madhi SA, Polack FP, Piedra PA, et al. Respiratory syncytial virus vaccination during 
pregnancy and effects in infants. N Engl J Med. 2020;383(5):426-39.
34
Regen AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization 
during pregnancy in 4 high-income countries, 2010–2016.  Clin Infect Dis.
2018;67(12):1915-8.
35
Pettker CM, Goldberg JD, El-Sayed YY, et al. Committee opinion number 700: methods 
for estimating the due date. Obstet Gynecol. 2017;129(5):e150-54.
36
European Commission. Ethical considerations for clinical trials on medicinal products
conducted with minors. Available from:
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/2017_09_18_ethical_consid_ct_with_minors.pdf. Published: 18 Sep 2017. Accessed:
21 Feb 2019.
37
Centers for Disease Control and Prevention. Metropolitan Atlanta congenital defects 
program. Available from: https://www.cdc.gov/ncbddd/birthdefects/macdp.html. 
Accessed: 09 Jun 2020.
38
Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: case definition & guidelines for 
data collection, analysis, and presentation of immunisation safety data. Vaccine.
2016;34(49):6047-56.
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Document Approval Record
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PPD
PPD

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine)
Protocol C3671008
Final Protocol Amendment 6, 01 June 2022
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLINDED,
PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND 
SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F 
SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING 
PREGNANCY
Investigational Product Number:
PF-06928316
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine
United States (US) Investigational New 
Drug (IND) Number:
017931
European Clinical Trials Database 
(EudraCT) Number:
2019-002943-85
Protocol Number:
C3671008
Phase:
3
Short Title: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants 
Born to Women Vaccinated During Pregnancy.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original 
protocol
05 December 2019
Not applicable (N/A)
Protocol 
Amendment 1
24 March 2020
PROTOCOL SUMMARY: Clarification text was 
added in various sections of the main body of the 
protocol to match the revisions made to the protocol 
summary.
Throughout: The protocol now contains final 
wording regarding the double-blinded, 
placebo-controlled study design and the final dose 
and formulation of the respiratory syncytial virus 
stabilized prefusion F subunit vaccine (RSVpreF). 
This is as a result of the analysis of the safety, 
tolerability, and immunogenicity data from the 
C3671003 maternal Phase 2b trial.
Section 1.2.1 Study Design – Maternal Participants: 
The final dose and formulation of RSVpreF were 
inserted, including the lyophile match for the 
placebo.
Section 1.2.2 Study Design – Infant Participants: The 
text box pertaining to the vaccine group arms was 
deleted. The maternal-infant dyads will be randomly 
assigned in this study. Rationale: Infant participants 
will not be administered the investigational product. 
Therefore, the current placement is potentially 
confusing to readers.
Section 1.2.3 Schedule of Activities for Maternal 
Participants, Section 5.2.3, and Section 8.10.1: 
Clarification text was added as follows:
o
The immunogenicity blood collection and 
physical examination window requirements 
before vaccination were aligned to provide 
greater logistical convenience for the 
investigational sites with respect to enrolling 
participants into the study.
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Document History
Document
Version Date
Summary of Changes and Rationale
o
The wording for the study objectives pertaining 
to the request for intrapartum antibiotic 
prophylaxis (IAP) details for maternal 
participants with a group B streptococcal (GBS) 
status was revised to be consistent with the study 
procedural objectives, which are to collect GBS 
status and to ascertain whether any medication 
was given for IAP. This resulted in the deletion 
of the text in Section 6.5.3, as this information is 
captured in Section 8.10.3.
o
A reference to the immunogenicity blood draws 
for maternal participants was added to clarify the 
adverse event (AE) reporting requirements for 
events that might occur as a result of 
study-related procedures.
Section 1.2.3.1 Schedule of Activities for Maternal 
Participants – Respiratory Tract Illness (RTI) 
Surveillance for Medically Attended Respiratory 
Tract Illness (MA-RTI) Visits:
o
Details to be collected during an MA-RTI were 
revised.
o
Clarification was added regarding the safety 
reporting requirements for MA-RTI events that 
might occur during the study.
Section 1.2.4 Schedule of Activities for Infant 
Participants:
o
Visit flexibility was increased to prioritize 
participant safety and adherence to local 
guidance in the event of a coronavirus disease 
2019 (COVID-19) outbreak or other outbreaks.
o
The physical examination and vital sign 
assessment windows for the study were aligned 
to provide greater logistical convenience for the 
investigational sites with respect to compliance to 
study protocol requirements.
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Document
Version Date
Summary of Changes and Rationale
o
The protocol safety reporting criteria and period 
for adverse events (AEs), serious adverse events 
(SAEs), and newly diagnosed chronic medical 
conditions (NDCMCs) were streamlined.
Section 1.2.4.1 Schedule of Activities for Infant 
Participants: RTI Study Visits During the Study: The 
table was revised, including splitting the schedules of 
activities for unscheduled RTI visits for all infant 
participants into RTI surveillance from birth to 
6 months and RTI surveillance from 6 months to the 
end of the study. The procedures were streamlined 
for these RTI study visits to improve clarity and 
consistency.
Table 1: Clarification has been added as to when a 
study visit is triggered for reported MA-RTI endpoint 
events on the study. Day 1 is the day of the MA-RTI 
visit as detailed in Section 8.11.7.
In addition, clarification has been added as to what 
constitutes the site source for confirmed study 
endpoint criteria, in order to provide the sites 
guidance on what documentation will eventually be 
submitted to the endpoint adjudication committee 
(EAC) for evaluation.
Section 3.1: The exploratory endpoints were revised 
to correspond with the planned statistical analyses of 
RTI events in the pediatric population. This does not 
represent a change to the study design but instead 
better reflects the total statistical analysis plan.
Section 3.1, Section 3.2, and throughout: To improve 
clarity and ensure consistency, the use of 
“RSV-neutralizing antibody titers” has been changed 
to RSV serum neutralizing titers.” This is the 
sponsor’s preference based on what the neutralizing 
activity assay is based upon, and in this case, it is 
whole serum and not just the purified antibodies 
during these immunogenicity assessments.
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Version Date
Summary of Changes and Rationale
Section 3.3, Section 8.1.1.2, Section 8.1.3, and 
Section 10.2: For further clarification, the protocol’s 
safety and endpoint reporting requirements were 
amended to ensure consistency with Pfizer’s updated 
safety reporting requirements for endpoint-defined 
studies.
Section 4.3: The text “availability of these data are
expected in 2020” was removed as this statement 
does not accurately reflect the current 
decision-making process for the dose and 
formulation selection activities for this study.
Section 5.2.1: Clarification text was added to the 
exclusion criterion for body mass index (BMI) and 
congenital anomalies based on study requirements.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: The 
tetanus, diphtheria, and acellular pertussis vaccine 
(Tdap) administration requirements text was 
modified to describe the timing of vaccinations based 
on data from the C3671004 study, once available. 
This change will better reflect clinical practice and 
will facilitate recruitment of suitable maternal 
participants for the study.
Section 6.1.1, Section 6.1.3, Section 8.4, and 
Section 8.10.1: Clarification text was added to 
address investigational product reconstitution volume 
and administration requirements. This change is to 
ensure consistency with the investigational product 
administration documentation for the study.
Section 7.2: Clarification text was added to address 
the notification process for biological sample 
management in the event of study participant 
withdrawal from the study.
Section 7.3 and Appendix 1 Informed Consent 
Process: Clarification text was added to address 
study retention and data collection requirements for 
the study. In addition, further clarification has been 
added to emphasize the informed consent process 
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Version Date
Summary of Changes and Rationale
during circumstances where the maternal participant 
is no longer able to provide consent but the infant 
participant’s continued participation in the study 
could be retained by the parent(s)/legal guardian as 
per local regulatory, local laws, and local governance 
approval.
Section 8.1.1.1: Clarification text was added to 
provide guidance regarding the midturbinate swab 
processing requirements and the definition of 
acceptable certified/accredited laboratory bodies for 
this process in the study.
Section 8.2.1.1 and Section 8.10.1: The reporting 
requirements for Grade 4 local reactions in the study 
were clarified; the assessment and reporting are 
carried out by the investigators (or appropriately 
qualified designees).
Section 8.3.1.1, Section 8.3.1.2, Section 8.3.5.1, 
Section 8.3.5.2, Section 8.10, and Section 8.11: The 
reporting requirements were clarified for this 
vulnerable patient population with regard to AEs and 
SAEs likely to occur in the study in women with 
gestational age (GA) eligibility criterion between 
24 0/7 and 36 0/7 weeks.
Section 8.3.6: Text was added to address and 
standardize reporting procedures for adverse events 
of special interest (AESIs) for this patient population.
Section 8.3.7 and Appendix 4: Several Pfizer text 
revisions were incorporated regarding device 
deficiencies and the safety reporting requirements for 
this study.
Section 8.10: The immunogenicity blood collection 
and physical examination window requirements 
before vaccination were aligned to provide greater 
logistical convenience for the investigational sites 
with respect to enrolling participants into the study.
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Version Date
Summary of Changes and Rationale
Section 8.10.1: The prepregnancy BMI text revisions 
in Section 5.2.1 were aligned with the study 
assessment requirements for maternal participants at 
screening.
Section 8.10.2, Section 8.10.3, Section 8.10.4, and 
Section 8.10.6: Clarification text was added to the 
MA-RTI reporting requirements for maternal 
participants in the study to provide guidance and 
ensure the investigational sites provide accurate 
information pertaining to these self-reported events.
Section 8.11.1 to Section 8.11.6: Clarification text 
was added (where applicable) to address the 
following study assessments:
o
“Birth weight must be the first birth weight and 
cannot be based on the standard-of-care 
examination” was removed as this statement is 
confusing to the investigational sites. Birth 
weight assessments have now been realigned 
with standard-of-care assessments at the study 
visit to aid compliance with study assessments 
and requirements.
o
Clarification text was added regarding the 
reporting of standard-of-care measurements for 
vital sign assessments.
o
In addition, the physical examination and vital 
sign assessment windows for the study were 
aligned to provide greater logistical convenience 
for the investigational sites to comply with study 
protocol requirements.
o
For further clarification, the RTI study visit 
assessment requirements were amended to 
emphasize the difference between the MA-RTI 
visit criteria and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements.
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Version Date
Summary of Changes and Rationale
Section 8.11.7.1: For further clarification, the RTI 
study visit assessment requirements have been 
amended to emphasize the following:
o
The RTI study visit window, including nasal 
swab collection from the MA-RTI notification 
for the infant participant.
o
Duplicate text was removed pertaining to the 
MA-RTI definition and the signs and symptoms 
of interest pertinent to an RTI study visit.
o
Guidance regarding the difference between the 
MA-RTI visit and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements.
Section 8.11.8: Clarification text was added to 
address the RTI study visit window, including nasal 
swab collection from the MA-RTI notification for the 
infant participant.
o
For further clarification, the RTI study visit 
assessment requirements have been amended to 
emphasize the difference between the MA-RTI 
visit and the subsequent study visit after the event 
has been reported. This is to improve clarity and 
consistency with the RTI study visit requirements 
and provide guidance to the investigational sites.
Section 9.1.2.1, Section 9.1.2.2, Section 9.4.1, 
Section 9.2, and Section 9.5: Text was added to 
clarify the statistical analysis procedures in line with 
the current revisions.
Appendix 2: Clarification text was added to support 
the safety and pregnancy outcome reporting 
requirements for participants who may experience 
exposure during pregnancy while in the study.
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Appendix 5: Further clarification was added to the 
background factors of interest during the infant’s 
participation in the study.
Appendix 6: Clarification text was added to the 
examination and treatment criteria checklist for 
reported MA-RTI visits. This is to ensure there is 
some consistency to the source records provided for 
these events in relation to the protocol requirements.
Throughout: Several changes were made to 
incorporate the replacement of the Clinical Trial 
Serious Adverse Event Report Form (CT SAE 
Report Form) to Vaccine SAE Reporting Form, as 
part of the new vaccine SAE reporting requirements 
for Pfizer.
Throughout: Minor editorial revisions were 
incorporated as appropriate.
Protocol 
Amendment 2
26 June 2020
Section 5.1.1: Administrative update was 
incorporated to address the recently added 
Appendices 7 and 8.
Appendix 7: A country-specific appendix was added 
for Japan to address consent/assent issues for minors, 
temperature measurement, definition of fever, and 
enrollment of maternal participants in the sentinel 
cohort for safety monitoring.
Appendix 8: A country-specific appendix was added 
for the Gambia and South Africa to address an 
extension to the screening period for maternal 
participants with regard to GA requirements and 
consent process.
Protocol 
Amendment 3
26 August 2020
PROTOCOL SUMMARY: Added clarification text 
to the exploratory endpoint section for the infant 
participants; changes were made in the protocol 
summary to match the revisions made in the main 
body of the protocol.
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Section 1.2.2: Study Design – Infant Participants: 
Added text to address RSV seasonality and the 
required RTI surveillance periods during the study. 
Rationale: The previous placement was potentially 
confusing to readers. The revisions provide clarity to 
the investigational sites with regard to the RTI 
surveillance follow-up activities.
Section 1.2.3 and Section 1.2.3.1: Added clarification 
text (where applicable) to address the following:
o
Added “Home or Telephone” to the type of visit 
options allowed for the 6-month-postdelivery 
visit.
o
Added clarification text to the alcohol history 
reporting requirements and included “obstetric” 
in the screening assessment requirements for the 
study.
o
Added “study staff,” as study personnel are 
allowed to collect and report baseline and 
reactogenicity assessments reported during the 
evaluation period.
o
Added clarification text regarding the reporting 
requirements for AEs, SAEs, and MA-RTIs for 
maternal participants.
Section 1.2.4 - Schedule of Activities for Infant 
Participants:
o
Added “Home” to the type of visit options 
allowed for the 1-month and 6-month follow-up 
visits and added further clarification to the visit 
status during potential COVID-19 pandemic 
situations or other natural disasters. Rationale: 
Infant participant visit options were aligned with 
the maternal participant requirements to allow for 
visit flexibility.
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o
For further clarification, the physical examination 
and vital sign assessment expectations at birth 
and at the 1-month visit were aligned to provide 
greater logistical convenience for the 
investigational sites to comply with study 
protocol requirements.
Sections 1.2.4, 1.2.4.1, 8.1.1, and 8.11 to 8.12:
Added clarification text (where applicable).
o
To address alternate nasal swab collection 
procedures, if needed, during potential 
COVID-19 pandemic situations or other natural 
disasters.
o
Clarification text was added with regards to the 
start of the reporting period for MA-RTI events 
upon the infant’s delivery. This is to improve 
clarity and consistency with the capturing and 
reporting requirements for MA-RTI events and 
provide guidance to the investigational sites.
Sections 1.2.4.1, 8.11.7.1, 8.11.8, and Appendix 6:
o
Added temperature and body weight 
measurements for infant participants during study 
RTI visits.
o
For vital sign measurements, especially oxygen 
saturation measurements (where applicable), 
clarification text was added to state that it is 
recommended that the participant not be 
receiving supplemental oxygen at the time of 
measurement.
These updates are to ensure consistency with the 
study RTI assessment visits after a confirmed 
MA-RTI event.
Section 3.1: Added clarification text as follows:
o
Table 1.  Primary and Secondary Endpoint 
Events and Definitions in Infant Participants: For 
further clarification, added descriptive text to the 
table header to address endpoint events listed 
within the table. In addition, made corrections to 
the overlapping respiratory rate measurements 
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provided for some study endpoint events. These 
changes were made to improve clarity and 
consistency with the endpoint reporting and 
evaluation process for the study.
o
For the infant participant exploratory objectives,
added the planned statistical analysis period of
“after 6 months of age” to “all-cause MA-RTIs 
and hospitalizations due to RSV” in the pediatric 
population based on regulatory authority 
feedback from South Korea.
o
Incorporated revisions to align endpoints with 
study duration, specifically MA-LRTIs due to 
RSV A and RSV B, and MA-RTIs associated 
with non-RSV respiratory pathogens.
o
Added clarification text to address the analysis 
plans for the healthcare utilization endpoints.
Section 4.1: For further clarification, added text to 
address the desire to enroll across gestational age.
Section 4.3: Added a brief summary of the safety and 
immunogenicity results from the C3671003 trial to 
support the decision-making process for this study.
Section 5.1.1: Inserted administrative 
update/clarification text with regards to:
o
Participant eligibility guidance documentation 
available within the investigator site file.
o
The informed consent process for maternal 
participants.
Section 5.2.1: Based on study requirements:

Added clarification text to exclusion criterion 7, 
which addresses the investigator’s judgment 
when assessing participant eligibility (maternal 
participant or her fetus) and regional endemic 
conditions during routine maternal care, as per 
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local standards of care and obstetric 
recommendations.

Added clarification text to address illicit drug use 
pertaining to marijuana.
Section 5.2.2: Deleted the infant participants 
exclusionary criterion pertaining to the “receipt of 
investigational or approved monoclonal antibodies 
against RSV.” This was to provide additional 
clarification to the investigational sites with regards 
to the infant’s eligibility criteria.
Sections 5.2.3, 6.5.1, and 6.5.2: Modified the Tdap 
administration requirements text to describe the 
timing of vaccinations based on recent data from the 
C3671004 study (A Phase 2b, Placebo-Controlled, 
Randomized, Observer-Blind Study to Evaluate the 
Safety, Tolerability, and Immunogenicity of a 
Respiratory Syncytial Virus (RSV) Vaccine When 
Administered Concomitantly With Tetanus, 
Diphtheria, and Acellular Pertussis Vaccine (Tdap) 
in Healthy Nonpregnant Women 18 Through 
49 Years of Age; ClinicalTrials.gov identifier: 
NCT04071158).
Section 6.1.4: Added text to clarify what constitutes 
a medical device with regards to the investigational 
product in this study.
Section 6.5.2: Added text to clarify the tetanus and 
diphtheria vaccine administration requirements 
during the study.
Section 6.5.4: For further clarification, added text to 
address prohibited vaccinations and treatments for 
infant participants. This is to provide guidance to the 
investigational sites.
Section 6.5.5: Added text to clarify the permitted 
treatments, vaccines, and procedures acceptable to 
infant participants enrolled in the study.
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Sections 8.2.1 to 8.2.1.2 and Section 8.10.1: For 
further clarification, amended the e-diary completion 
requirements to emphasize the different reporting 
and/recording options for reactogenicity events 
should illiterate maternal participants be enrolled in 
the study. This is to improve clarity and consistency 
with the reactogenicity reporting requirements at the 
investigational sites.
Table 6 and Section 8.2.1.3: Based on regulatory 
feedback, provided a description of the intensity 
scale for the reactogenicity event “fever.”
Sections 8.3.1 to 8.3.1.2, Sections 8.3.5.2 to 8.3.8.1, 
and Section 10.2.3: Added clarification text (where 
applicable) to address the following safety-related 
updates and provide guidance to the investigational 
sites:
o
Several Pfizer text revisions were incorporated 
regarding the safety reporting requirements for 
this study.
o
Text was added to clarify the SAE reporting 
timelines for the study and provide guidance 
regarding the evaluation of and assessment 
procedures for congenital anomalies.
Section 8.10.1: For further clarification, aligned the 
study assessment window requirements before 
vaccination to provide guidance and greater logistical 
convenience for the investigational sites with respect 
to enrolling participants into the study.
Section 8.10.3: Added clarification text with regards 
to the reporting requirements for maternal 
participants diagnosed as GBS positive and 
pregnancy outcome information. This is to improve 
clarity and consistency with the reporting 
requirements at investigational sites.
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Section 8.11.1: Added clarification text on how the 
infant participant’s identifier will be assigned for this 
study.
Sections 8.11.1 to 8.11.6: Added clarification 
regarding the reporting of standard-of-care 
measurements for vital sign assessments, 
measurements, and physical examination procedures
(where applicable) to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 9.2 and Section 9.4.1: Modified text to more 
generally describe Type 1 error control procedures 
and refer to the statistical analysis plan (SAP) for 
details.
Section 9.4.3.2: Added clarification regarding the 
planned analyses for the healthcare utilization 
endpoints.
Section 10.2.5: Deleted the “SAE Reporting to Pfizer 
Safety via an Electronic Data Collection Tool” 
section. For consistency, only the Vaccine SAE 
Reporting Form process will be used.
Appendix 6: Added clarification text to the 
microbiological data collection requirements for the 
study based on any pathogen-related 
assessments/findings performed as part of the 
participant’s routine clinical care. This is to ensure 
there is some consistency to the source records 
provided for these events in relation to the protocol 
requirements and to address regulatory guidance in 
light of the COVID-19 outbreak or other outbreaks.
Appendix 7: Added clarification text to the 
following:
o
Incorporated minor editorial revisions into the 
Schedule of Activities for Maternal Participants 
Enrolled in the Sentinel Cohort in Japan.
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o
Added clarification text to exclusion criterion 12 
regarding the definition of illicit drug use based 
on country-specific requirements.
o
Incorporated clarification text regarding the 
definition of an SAE caused by a medical device.
Appendix 9: Added a country-specific appendix for 
South Korea and Taiwan to address the minimum 
age requirements for maternal participants in each 
country.
Throughout: Incorporated minor editorial revisions 
as appropriate.
Protocol 
Amendment 4
22 March 2021
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made in 
the main body of the protocol.
Section 1.2.3: Added text to address safety reporting 
requirements during consent/assent for minors 
enrolled as maternal participants in the study.
Section 2.1: Added text to address the enrollment of 
adolescent menarchal females into the study, ie, no 
lower age limit for maternal participants. This is 
based on recent regulatory feedback regarding the 
study design for RSVpreF evaluation in pregnant 
adolescent females.
Section 3.1 and Section 9.4.1: The secondary and 
exploratory endpoints were revised to correspond 
with the planned statistical analyses of RTI events in 
the pediatric population:
o
Updated secondary objectives pertaining to 
hospitalization and MA-LRTI due to any cause, 
extended the efficacy analysis to be in line with 
the duration of follow-up for infant participants 
during the first year of their participation in the 
study, which is 360 days after birth.
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o
An additional secondary objective added to 
assess the efficacy of RSVpreF in reducing the 
incidence of MA-LRTI due to RSV.
o
An additional exploratory objective added to 
assess the efficacy of RSVpreF in reducing the 
incidence of MA-RTI, MA-LRTI, and severe 
MA-LRTI in premature infants 37 weeks of 
age.
These updates are reflected in the statistical section 
of the protocol and do not represent a change to the 
study design but instead better reflect the total 
statistical analysis plan.
Section 4.1: For further clarification, added text to 
address the consent/assent requirements for minors 
enrolled as maternal participants in the study.
Section 4.1 and Section 4.1.2: Given the COVID-19 
pandemic situation, and the variable RSV season, the 
maternal participant sample size on the study may 
need to be increased and enrollment could possibly 
go up to 10,000 maternal participants.
Section 4.4: Added text to clarify the study definition 
for a completed maternal/infant participant in the 
study.
Section 5.1.1: Added clarification with regards to
inclusion criteria and incorporated administrative 
update:
o
Removed the lower age limit for healthy pregnant 
females likely to be eligible for enrollment in the 
study. This change will facilitate recruitment of 
suitable maternal participants for the study.
o
Allowed the GA determination to be based upon 
the first trimester ultrasound examination alone, 
without the last menstrual period, in countries 
where this is routine. This is to improve clarity 
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and consistency with the GA determination 
requirements at the investigational sites.
o
Updated criterion 4 regarding fetal anomaly 
ultrasound examination requirements in the 
study. This is to improve clarity and ensure 
consistency with study requirements at 
investigational sites.
Section 5.2.1: Incorporated administrative update and
clarification with regards to:
o
Marijuana use and maternal participant eligibility
in the study.
o
The use of licensed COVID-19 vaccines or 
COVID-19 vaccines authorized for temporary, or 
emergency use based on regulatory and national 
recommendations in maternal participants 
enrolled into the study.
This was to provide additional clarification to the 
investigational sites with regards to the eligibility 
criteria of maternal participants.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: Due 
to the current COVID-19 pandemic, added text to 
clarify the vaccination delay criteria and nonvaccine 
administration window for maternal participants 
receiving licensed COVID-19 vaccines or 
COVID-19 vaccines authorized for temporary or 
emergency use. This change is consistent with other 
nonstudy vaccines allowed in the study.
Section 6.3.1, Section 8.1.2, Section 8.2.1 to 
Section 8.2.1.3, Section 8.3, Section 8.3.1, 
Section 8.3.1.2, Section 8.10.1 to Section 8.10.6,
and Section 10.1.3: Added text to clarify the 
consent/assent requirements during study 
procedures/assessments in the event “a minor” is 
enrolled as a maternal participant. This is to improve 
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clarity and ensure consistency for the investigational 
sites to comply with study protocol requirements.
Section 8.3.8.1: Added text to make the following 
safety-related updates and provide guidance to the 
investigational sites:
o
Incorporated safety reporting text for participants 
who report a positive test result for severe acute 
respiratory syndrome coronavirus 2 
(SARS-CoV-2) during the study.
o
Text was added to clarify the AESI reporting 
requirements for the study and provide guidance 
regarding the definition of and categorization of 
a developmental delay in infant participants.
Section 8.10.1: Incorporated administrative update 
regarding which body systems are deemed 
mandatory and which discretionary during physical 
examination procedures for maternal participants in 
the study. This is to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 8.11.1: Incorporated text regarding the 
reporting of standard-of-care measurements for vital 
sign and physical examination procedures at the 
infant’s birth. This is to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 8.11.7, Section 8.11.8, and Section 8.12: 
Added text to clarify the nasal swab collection 
requirements from infant participants during a 
confirmed MA-RTI episode.  This is to provide 
flexibility and prioritize participant safety during 
the study.
Section 9.3, Section 9.4.2, Section 9.4.3, and 
Section 9.4.3.2: Added text to clarify the statistical 
analysis procedures in line with the current revisions.
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Appendix 7 and Appendix 9: Removed the lower 
age limit for healthy pregnant females likely to be 
eligible for enrollment into the study. In addition, 
incorporated minor editorial revisions to the 
informed consent document for maternal participants 
enrolled in Japan only.
Appendix 8: Added the Philippines to the list of 
countries impacted by an extension to the screening 
period for maternal participants with regard to GA 
requirements and consent process.
Throughout: Incorporated minor editorial revisions
as appropriate.
Protocol 
Amendment 5
12 January 2022
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made in 
the main body of the protocol.
Section 1.1 and Section 3.1: Typographical error 
with the third secondary efficacy endpoint pertaining 
to endpoint adjudication committee (EAC) activities 
was removed to align with the protocol defined
procedures and SAP.
Section 5.2.3: Administrative update to clarify the 
coadministration window requirements for licensed 
COVID-19 vaccines and COVID-19 vaccines 
authorized for temporary or emergency use, based 
on evolving regulatory and national guidelines.
Section 6.5.1 and Section 6.5.2: Added text to clarify 
the coadministration requirements for any licensed 
vaccines containing pertussis in maternal participants 
likely to be eligible for the study.
Section 1.1, Section 4.1, Section 9.2, Section 9.4.1, 
and Section 9.5: Modified text to address additional 
interim analyses planned for the study.
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Appendix 10: Added a country-specific appendix for 
South Korea to address marijuana use and maternal 
participant eligibility in the study.
Appendix 11: Added a country-specific appendix for 
The Philippines at the request of the Philippine 
Health Research Ethics Board (PHREB) that clarifies 
the compensation/reimbursement requirements for 
participants enrolled in the Philippines based on 
national regulatory laws and recommendations.
Protocol 
Amendment 6
01 June 2022
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made 
in the main body of the protocol.
Section 1.2.4: Updated the window of assessment for 
infant physical examination from 48 to 72 hours to
reflect the current entry in Section 8.11.1.  
Section 1.2.4.1: Revisions were made to the 
Schedule of Activities for Infant Participants to 
clarify language related to RTI assessments.
Section 2.2, Section 4.1, and Section 4.1.2: Modified 
language to justify a new enrollment strategy and 
endpoint case-accrual plan.
Section 5.2.1: Added text to exclusion criterion 11 to 
clarify that maternal participants who have 
previously received SARS-CoV-2 monoclonal 
antibodies as part of their COVID-19 treatment, 
postexposure prophylaxis, or preexposure 
prophylaxis are now permitted to be enrolled in the 
study.
Section 9.2, Section 9.4.1, and Section 9.5: Modified 
text to address final analyses planned for the study.
Section 10.1.5: Several Pfizer protocol template text 
revisions were incorporated pertaining to the 
dissemination of clinical study data.
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This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................30
1. PROTOCOL SUMMARY...................................................................................................31
1.1. Synopsis ..................................................................................................................31
1.2. Schematic for Study Participants ............................................................................40
1.2.1. Study Design – Maternal Participants ........................................................40
1.2.2. Study Design – Infant Participants .............................................................41
1.2.3. Schedule of Activities for Maternal Participants........................................42
1.2.3.1. Schedule of Activities for Maternal Participants: RTI 
Surveillance for Medically Attended Respiratory Tract Illness 
Visits (Vaccination Until the End-of-Study Visit) ............................45
1.2.4. Schedule of Activities for Infant Participants.............................................46
1.2.4.1. Schedule of Activities for Infant Participants: Respiratory 
Tract Illness Study Visits During the Study......................................48
2. INTRODUCTION ...............................................................................................................51
2.1. Study Rationale .......................................................................................................52
2.2. Background .............................................................................................................52
2.3. Benefit/Risk Assessment.........................................................................................53
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................55
3.1. Infant Participants ...................................................................................................55
3.2. Maternal Participants...............................................................................................61
3.3. Protocol-Defined Efficacy Endpoints .....................................................................62
4. STUDY DESIGN.................................................................................................................62
4.1. Overall Design.........................................................................................................62
4.1.1. Approximate Duration of Participation for Each Participant .....................64
4.1.2. Approximate Number of Participants.........................................................64
4.2. Scientific Rationale for Study Design.....................................................................64
4.3. Justification for Dose ..............................................................................................64
4.4. End of Study Definition ..........................................................................................66
5. STUDY POPULATION......................................................................................................66
5.1. Inclusion Criteria.....................................................................................................67
5.1.1. Inclusion Criteria – Maternal Participants..................................................67
5.1.2. Inclusion Criteria – Infant Participants.......................................................69
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5.2. Exclusion Criteria....................................................................................................69
5.2.1. Exclusion Criteria – Maternal Participants.................................................69
5.2.2. Exclusion Criteria – Infant Participants......................................................71
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants ................72
5.3. Lifestyle Considerations..........................................................................................72
5.4. Screen Failures ........................................................................................................72
6. STUDY INTERVENTION..................................................................................................72
6.1. Study Intervention(s) Administered........................................................................73
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........73
6.1.2. Placebo........................................................................................................73
6.1.3. Administration............................................................................................73
6.1.4. Medical Devices .........................................................................................74
6.2. Preparation/Handling/Storage/Accountability ........................................................74
6.2.1. Preparation and Dispensing........................................................................75
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................75
6.3.1. Blinding of Study Site Personnel................................................................75
6.3.2. Blinding of the Sponsor..............................................................................76
6.3.3. Allocation to Investigational Product .........................................................76
6.3.4. Breaking the Blind......................................................................................76
6.4. Study Intervention Compliance...............................................................................77
6.5. Concomitant Therapy..............................................................................................77
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................77
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................77
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................78
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................78
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................78
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications –
Infant Participants............................................................................................78
6.6. Dose Modification...................................................................................................79
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6.7. Intervention After the End of the Study..................................................................79
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................79
7.1. Discontinuation of Study Intervention ....................................................................79
7.2. Participant Discontinuation/Withdrawal From the Study.......................................79
7.3. Withdrawal of Consent............................................................................................80
7.4. Lost to Follow-up....................................................................................................80
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................80
8.1. Efficacy Assessments..............................................................................................81
8.1.1. Efficacy Assessments – Infant Participants................................................81
8.1.1.1. Midturbinate Nasal Swab Collection and Testing 
Requirements for Endpoint Confirmation – Infant Participants........82
8.1.1.2. Events for Adjudication and Submission Guidance –
Infant Participants..............................................................................83
8.1.2. Exploratory Efficacy Assessments – Maternal Participants.......................83
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal 
and Infant Participants .....................................................................................84
8.1.4. Immunogenicity Assessments ....................................................................84
8.1.4.1. Total Volume of Blood Collected – Maternal Participants.......84
8.1.4.2. Total Volume of Blood Collected – Infant Participants............84
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant 
Participants ........................................................................................85
8.1.4.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development – Maternal and Infant 
Participants ........................................................................................85
8.1.4.5. Respiratory Pathogens – Infant Participants .............................85
8.1.4.6. Biological Samples – Maternal and Infant Participants............86
8.2. Safety Assessments .................................................................................................86
8.2.1. Participant Electronic Diary – Maternal Participants .................................86
8.2.1.1. Local Reactions – Maternal Participants...................................87
8.2.1.2. Systemic Events – Maternal Participants..................................89
8.2.1.3. Temperature – Maternal Participants ........................................90
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant 
Participants.......................................................................................................91
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8.3. Adverse Events and Serious Adverse Events..........................................................92
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......92
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................94
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................94
8.3.2. Method of Detecting AEs and SAEs ..........................................................95
8.3.3. Follow-up of AEs and SAEs.......................................................................95
8.3.4. Regulatory Reporting Requirements for SAEs...........................................96
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Investigational Product ..........................................................................96
8.3.5.1. Exposure During Breastfeeding ................................................96
8.3.5.2. Occupational Exposure .............................................................96
8.3.6. Cardiovascular and Death Events...............................................................97
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................97
8.3.8. Adverse Events of Special Interest.............................................................98
8.3.8.1. Lack of Efficacy........................................................................98
8.3.9. Medical Device Deficiencies......................................................................99
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........99
8.3.9.2. Follow-up of Medical Device Deficiencies...............................99
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................99
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies .....................................................................................100
8.3.10. Medication Errors...................................................................................100
8.4. Treatment of Overdose..........................................................................................101
8.5. Pharmacokinetics ..................................................................................................101
8.6. Pharmacodynamics................................................................................................101
8.7. Genetics.................................................................................................................101
8.7.1. Specified Genetics ....................................................................................101
8.8. Biomarkers ............................................................................................................101
8.9. Health Economics .................................................................................................102
8.10. Procedures – Maternal Participants.....................................................................102
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8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to 
Vaccination to Day 1 – Visit 1) .....................................................................102
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After 
Vaccination)...................................................................................................106
8.10.3. Delivery (Maternity Unit).......................................................................107
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 
210 Days After Delivery)...............................................................................108
8.10.5. Unscheduled Reactogenicity Visits........................................................109
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria –
Maternal Participants .....................................................................................111
8.11. Procedures – Infant Participants..........................................................................112
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After 
Birth)..............................................................................................................112
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After 
Birth)..............................................................................................................113
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 
Days After Birth) ...........................................................................................115
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 
Days After Birth) ...........................................................................................116
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days 
After Birth; Infant Participants Born During the First Year of the Study 
Only) ..............................................................................................................117
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 
742 Days After Birth; Infant Participants Born During the First Year of 
the Study).......................................................................................................118
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 
6 Months After Delivery)...............................................................................119
8.11.7.1. Study Visits Following a Medically Attended RTI –
Hospital, Home, or Clinic Visit.......................................................119
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit 
Criteria ...........................................................................................................121
8.12. Nasal Swab Collection ........................................................................................122
8.13. Communication and Use of Technology.............................................................123
9. STATISTICAL CONSIDERATIONS ..............................................................................124
9.1. Estimands and Statistical Hypotheses...................................................................124
9.1.1. Estimands – Infant Participants ................................................................124
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9.1.1.1. Efficacy ...................................................................................124
9.1.1.2. Immunogenicity ......................................................................125
9.1.1.3. Safety.......................................................................................125
9.1.2. Estimands – Maternal Participants ...........................................................125
9.1.2.1. Immunogenicity ......................................................................125
9.1.2.2. Safety.......................................................................................126
9.2. Sample Size Determination...................................................................................126
9.3. Populations for Analysis .......................................................................................127
9.4. Statistical Analyses ...............................................................................................128
9.4.1. Efficacy Analyses .....................................................................................128
9.4.2. Safety Analyses ........................................................................................131
9.4.3. Other Analyses..........................................................................................132
9.4.3.1. Immunogenicity Analyses.......................................................132
9.4.3.2. Healthcare Utilization Analyses..............................................133
9.5. Interim Analyses ...................................................................................................134
9.5.1. Data Monitoring Committee.....................................................................135
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................136
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............136
10.1.1. Regulatory and Ethical Considerations ..................................................136
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................137
10.1.2. Financial Disclosure ...............................................................................137
10.1.3. Informed Consent Process ......................................................................137
10.1.4. Data Protection .......................................................................................139
10.1.5. Dissemination of Clinical Study Data ....................................................139
10.1.6. Data Quality Assurance ..........................................................................140
10.1.7. Source Documents..................................................................................141
10.1.8. Study and Site Closure............................................................................142
10.1.9. Publication Policy...................................................................................142
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................143
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................143
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10.2.1. Definition of AE .....................................................................................144
10.2.2. Newly Diagnosed Chronic Medical Conditions.....................................145
10.2.3. Definition of SAE...................................................................................145
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs.....................147
10.2.5. Reporting of SAEs..................................................................................150
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......150
10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting............................................152
10.4.1. Definition of AE and ADE .....................................................................152
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device 
Effect, and Unanticipated Serious Adverse Device Effect............................153
10.4.3. Definition of Device Deficiency.............................................................153
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................154
10.4.5. Reporting of SAEs..................................................................................156
10.4.6. Reporting of SADEs...............................................................................156
10.5. Appendix 5: Background Factors........................................................................157
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria 
Checklist for MA-RTI Visit – Infant Participants...................................................157
10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only...............159
10.7.1. Informed Consent for the Maternal Participants <20 Years Old............159
10.7.2. Temperature Measurement and Definition of Fever ..............................160
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants.........160
10.7.3.1. Enrollment of Maternal Participants in the Sentinel 
Cohort..............................................................................................161
10.7.3.2. Conclusion of the Sentinel Cohort ........................................161
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or 
Telephone; 14 to 16 Days After Vaccination).................................161
10.7.3.4. Schedule of Activities for Maternal Participants Enrolled 
in the Sentinel Cohort in Japan........................................................162
10.7.4. Exclusion Criterion 12 Clarification.......................................................165
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and 
Unanticipated SAE Caused by Medical Device ............................................165
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix –
Applicable to the Philippines, Gambia, and South Africa Only..............................165
10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to 
South Korea and Taiwan Only ................................................................................166
10.10. Appendix 10: Country-Specific Appendix – Applicable to South Korea 
Only.........................................................................................................................166
10.11. Appendix 11: Country-Specific Appendix – Applicable to the Philippines 
Only.........................................................................................................................167
10.12. Appendix 12: Abbreviations .............................................................................168
11. REFERENCES ................................................................................................................171
LIST OF TABLES
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants ...............................................................................................55
Table 2.
Endpoint Events and Definitions in Maternal Participants.......................61
Table 3.
Guideline for Infant Blood Draw, If Cord Blood Sample Was Not 
Obtained....................................................................................................85
Table 4.
Grading Scale for Local Reactions...........................................................88
Table 5.
Grading Scale for Systemic Events ..........................................................90
Table 6.
Ranges for Fever.......................................................................................91
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals 
at an Interim Analysis.............................................................................135
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1. PROTOCOL SUMMARY
1.1. Synopsis
Indication
Pfizer’s respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSVpreF) 
is a prophylactic vaccine that is being investigated for the prevention of medically attended
RSV-associated lower respiratory tract illness (LRTI) in infants by active immunization of 
pregnant women.
Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given the global burden of disease, maternal immunization offers an attractive 
strategy for infant disease prevention.  Both preclinical studies in animals and interim data 
from a Phase 1/2 study in healthy nonpregnant adults have demonstrated acceptable 
tolerability and safety of RSVpreF.  A robust immune response has also been observed in 
participants from the aforementioned trial. RSVpreF is currently under assessment in healthy 
pregnant women 18 through 49 years of age (Study C3671003: A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blinded Trial to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT04032093).
The safety and tolerability of RSVpreF in pregnant adolescents has yet to be demonstrated. 
Vaccine-elicited immune responses with RSVpreF are expected to be similar in adolescents 
and women based on studies comparing maternal immunization with Tdap and HPV 
vaccination.  Infants born to adolescent mothers are known to be at a higher risk of 
prematurity, an important risk factor for RSV disease. Therefore, pregnant adolescents 
(18 years of age) are an appropriate pediatric population for RSVpreF maternal 
immunization, providing insight toward the efficacy, safety, and tolerability of the vaccine.
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
lower respiratory tract illness (MA-LRTI) in infants.
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Objectives, Estimands, and Endpoints
Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC):

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants 
born to maternal 
participants receiving 
1 dose of investigational 
product, the percentage 
of participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

Adverse events (AEs) from birth to 
1 month of age.

Serious adverse events (SAEs) and 
newly diagnosed chronic medical 
conditions (NDCMCs):
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants 
enrolled during the first year of 
the study).
Secondary Efficacy Objectives
– Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth,
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI:

occurring within 210 days after birth.

occurring within 240 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 270 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 270 days meets 
efficacy criteria.
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Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of medically attended 
respiratory tract illness 
(MA-RTI) due to RSV.
RSV-positive MA-RTI:

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs 
from vaccination up to 730 days after 
birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 12 months 
of age.
MA-LRTIs due to RSV occurring 361 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV in infants after 6 months 
of age.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA--LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
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To assess the impact of 
RSVpreF on RSV illness based 
on socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
To assess the effect of RSVpreF 
on healthcare utilization.
Univariate summaries of healthcare 
utilization variables, which may include 
the following: number and type of 
medical visits, length of hospital stay, 
requirement for mechanical ventilation, 
requirement for respiratory diagnostic 
procedures, requirement for intravenous 
(IV) fluids, requirement for prescriptions, 
and antibiotic use.
To describe the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI, 
MA-LRTI, and severe 
MA-LRTI in premature infants 
37 weeks of age.
MA-RTI, MA-LRTI, and severe 
MA-LRTI due to RSV occurring 0 to 
730 days after birth.
Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimand
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery 
study visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum
neutralizing titers and prefusion F 
immunoglobulin G (IgG) titers 
measured:

before vaccination.

at delivery.
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Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
This is an event-driven study with a target of at least 67 adjudicated (primary-endpoint) cases 
of MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis section [Section 9.2]). However, the final analysis will be 
performed at the end of the 2022 southern hemisphere RSV season, if fewer than 67 cases 
have occurred at that point.  There is no specific case target for the additional primary 
endpoint of severe MA-LRTI. The total enrollment number of maternal participants may 
vary depending on the incidence rate of the primary endpoint in the infant participants, the 
true underlying VE, and a potential early stop for efficacy or futility. In the event that 
efficacy in the infant population is demonstrated at an interim analysis, enrollment of 
maternal participants may continue in order to obtain safety evaluations in an adequate 
number of maternal and infant participants to support vaccine registration with national 
health authorities.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It was anticipated that approximately 
6900 mother-infant pairs would be needed to accumulate the original target of 
124 per-protocol cases prior to the global COVID-19 pandemic.  With the variable RSV 
season, the sample size is now expected to accrue at least 67 per-protocol cases. However,
with further variations in RSV seasonality, the sample size may need to be increased and 
enrollment could go up to 10,000 maternal participants based on the number of cases of 
RSV.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF will be 120 µg 
(60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants. Note: Maternal participants 
will include adolescent females who may be referred to as “minors.” 
Information/assessments for minors may require parental/legal guardian 
awareness/approval per local regulations.
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Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study, all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term respiratory 
tract illness (RTI) surveillance and safety oversight to address safety and the possibility of 
conferred enhanced protection (antibody persistence) during a second RSV season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee.
Planned Duration
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on gestational age (GA) at the time of vaccination and 
when the infant is actually born.
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
Data Monitoring Committee
This study will use an external data monitoring committee (E-DMC) to monitor vaccine 
safety and efficacy and study futility.
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Statistical Methods
The primary hypothesis to be tested is that VE with respect to MA-LRTI due to RSV or 
severe MA-LRTI due to RSV in infants within at least 90 days after birth is more than 20%, 
relative to placebo. The 2 primary endpoints will be tested in parallel using a multiplicity 
adjustment procedure. VE will be estimated using the exact conditional binomial method. 
There will also be hierarchical testing of the primary endpoints to 120 days, 150 days, and 
180 days, conditional on success of the analysis for the shorter intervals. Interim analyses of 
the MA-LRTI-due-to-RSV endpoint with the opportunity to stop the study for efficacy or 
futility may be included. At the end of the trial, the RSV vaccine may be deemed efficacious 
if there are 20 or fewer cases of MA-LRTI due to RSV in the RSV vaccine group out of the 
67 total primary-endpoint cases at 90 days.  This corresponds to estimated VE = 57% with 
97.6% confidence interval (CI) = (21%, 78%). For severe MA-LRTI, assuming a total of 
34 cases occur, the vaccine may be deemed efficacious if there are 8 or fewer cases in the 
RSV vaccine group.  This corresponds to estimated VE = 69% with 97.6% CI = (22%, 90%).
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1.2. Schematic for Study Participants
1.2.1. Study Design – Maternal Participants
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1.2.2. Study Design – Infant Participants
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Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
1.2.3. Schedule of Activities for Maternal Participants
Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier
X
Demography
X
Medical history including obstetric historyd
X
Record current/former alcohol, tobacco, marijuana, or any illicit drug 
usage
X
Record vital signs
X
Targeted physical and obstetric examination performed on the same 
day or within 7 days before the vaccination visit
X
Record details of any antenatal and/or postnatal steroid treatment, 
monoclonal antibodies, blood products, or Rho(D) immune globulin
X
X
X
X
Record details of the maternal participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
Review eligibility criteria
X
X
X
Review temporary delay criteria
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Prevaccination blood draw for serologic assessment (~15 mL) on the 
same day or within 7 days before the vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and measuring devicef
X
Obtain and record baseline assessment of prespecified systemic events 
on the day of and prior to vaccination in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic assessment (~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X---------------------------X
Record AEs, as appropriateh
X-------------------------- X
Record SAEs, as appropriateh
X
X
X
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of the 
schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; 
ICD = informed consent document; MA-RTI = medically attended respiratory tract illness.
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the LMP and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures and will be 
provided with instructions on their use. Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) a baseline 
assessment of prespecified systemic events on the day of and prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination 
(where Day 1 is the day of vaccination).  Remind maternal participants and their parent(s)/legal guardian (if a minor) that the study staff/field worker may 
contact them to obtain additional information on events entered into the e-diary.  Ask maternal participants or their parent(s)/legal guardian (if a minor) to 
contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 following vaccination, to determine if an 
unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal participant may be referred to the appropriate healthcare facility 
at the discretion of the study staff/field worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 28 days after vaccination.  From the signing of 
the ICD until the maternal participant completes the study, all SAEs will be collected. Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
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1.2.3.1. Schedule of Activities for Maternal Participants: RTI Surveillance for Medically Attended Respiratory Tract Illness
Visits (Vaccination Until the End-of-Study Visit)
Visit Description
Assessments of MA-RTIa
Visit Window
As Soon as Possible After Confirmed MA-RTI
Type of Visit
Telephone
Record details of a confirmed MA-RTI
X
Details of an acute illness visit AND a report of 1 or more of the following RTI
signs and symptoms:

New or increased sore throat

New or increased cough

New or increased nasal congestion

New or increased nasal discharge

New or increased wheezing

New or increased sputum production

New or increased shortness of breath
X
Obtain standard-of-care records, including local NAAT testing results 
(if applicable)b
X
Record nonstudy vaccine information
X
Record AEs and SAEs, as appropriatec
X
Complete the CRF with details
X
Abbreviations: CRF = case report form; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; 
RSV = respiratory syncytial virus; RTI = respiratory tract illness.
a.
Confirmed cases of MA-RTI will be collected from vaccination until the maternal participant completes the study. The assessment of the event would 
involve a telephone call, or a clinic visit if determined by the investigator to be warranted.
b.
Site staff will review and collect data pertaining to the illness and any local NAAT testing results (RSV, influenza, etc.), if available.
c.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  MA-RTI events will not be captured as safety 
events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to have resulted in death. Please see 
Section 8.3.1 for reporting requirements and timelines.
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1.2.4. Schedule of Activities for Infant Participants
Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 Days
After Birth
180 to 210 Days
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Assign infant participant identifier
X
Demography
X
Collect background factorsc
X
X
X
X
X
X
Collect birth outcome information including 
infant’s birth data and appearance, pulse, grimace, 
activity, and respiration (Apgar) score
X
Obtain and record infant’s length, head 
circumference, and weight
X
X
X
X
(if clinic visit)
X
(if clinic visit)
Physical examination including vital signs
(temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate) performed within 72 hours 
after birth
X
Obtain and record vital signs, including 
temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate
X
Targeted physical examination (record in the site 
source document)
X
X
X
(if clinic visit)
X
(if clinic visit)
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, 
packed cells)
X
X
X
X
X
X
Review eligibility
X
Cord blood sample (~10 mL) for serologic 
assessmentd
X
Record AEs, as appropriatee
X
Record NDCMCs and SAEs, as appropriatee
X
X
X
X
X
X
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Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 Days
After Birth
180 to 210 Days
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Surveillance reminder contact
Contact with the infant 
participants’ parent(s) or legal 
guardian(s) approximately 
every week until Visit 3
From Visit 3, contact with the infant participant’s parent(s) or legal guardian(s), 
approximately every 28 to 35 days until the end of the study
Assessment of MA-RTIsf,g
Assessment of MA-RTI events 
during the active RSV 
surveillance period as detailed 
in Section 1.2.4.1 of the 
schedule of activities
Assessment of MA-RTI events as detailed in Section 1.2.4.1 of the schedule of 
activities
Abbreviations: MA-RTI = medically attended respiratory tract illness; NDCMC = newly diagnosed chronic medical condition; 
RSV = respiratory syncytial virus; SpO2 = oxygen saturation.
a.
Applicable only for infant participants enrolled during the first year of the study.
b.
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), study visits that cannot be conducted in the clinic or at home, in 
accordance with the protocol requirements, may be conducted via telephone.
c.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV illness.
d.
Cord blood must be obtained on the day of birth. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical cord has 
been clamped and cut. If cord blood is unavailable, a blood sample may be collected from the infant participant preferably within the first 24 hours but up 
to 7 days after birth. The infant’s weight must be used to determine the volume of blood that can be collected.
e.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs, NDCMCs, and SAEs through 28 days after birth.  From 
29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected.  An NDCMC is defined as a disease or medical
condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
f.
A confirmed MA-RTI is defined as an expected study event based on the assessments detailed in the schedule of assessment in Section 1.2.4.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
g.
Reporting MA-RTI events should commence 72 hours after the infant’s delivery.  Respiratory distress events associated with and within 72 hours of birth 
should not be captured as MA-RTI events on the study but should be captured as AEs/SAEs (if applicable).
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1.2.4.1. Schedule of Activities for Infant Participants: Respiratory Tract Illness Study Visits During the Study 
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for All MA-RTIa
Hospital, Home, or Clinic
Follow-Up for
MA-RTI Visit
Telephone
RTI Study Visit for
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Surveillance reminder contact
Contact the infant participants’ parent(s) or 
legal guardian(s) approximately every week 
until Visit 3
From Visit 3, contact the infant participants’ parent(s) or legal 
guardian(s), approximately every 28 -35 days until the end of the 
study
Record confirmed MA-RTI as detailed in Appendix 6, as 
appropriate
X
X
X
Record details of the RTI, including 1 or more of the 
following RTI signs and symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid 
breathing for any duration

Cough

Inability to feed for any duration because of 
respiratory symptoms

Apnea

Any other respiratory symptom of concern
X
X
X
Obtain standard-of-care records and complete CRFc
X
X
X
Record local NAAT testing results, if performed and 
availabled
X
X
X
Perform RTI study visit, record targeted assessment
results (temperature, heart rate, respiratory rate, SpO2 by 
pulse oximetry, chest wall indrawing) and body weight, and 
collect nasal swab (for RT-PCR)e
X
X
Record concomitant medication associated with the 
treatment of the MA-RTI
X
X
X
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for All MA-RTIa
Hospital, Home, or Clinic
Follow-Up for
MA-RTI Visit
Telephone
RTI Study Visit for
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Collect background factors associated with MA-RTIf.
X
X
X
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, packed 
cells)
X
X
X
Record AEs , NDCMCs, and SAEs, as appropriateg
X
X
X
Compile MA-RTI visit source documentation upon 
request by adjudication committee (qualifying 
RSV-positive cases only)
X
X
Abbreviations: CRF = case report form; HCP = healthcare provider; ICU = intensive care unit; IV = intravenous; MA-LRTI = medically attended lower 
respiratory tract illness; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; NDCMC = newly diagnosed 
chronic medical condition; RSV = respiratory syncytial virus; RTI = respiratory tract illness; RT-PCR = reverse transcription–polymerase chain reaction; 
SpO2 = oxygen saturation.
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Final Protocol Amendment 6, 01 June 2022
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for All MA-RTIa
Hospital, Home, or Clinic
Follow-Up for
MA-RTI Visit
Telephone
RTI Study Visit for
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
a.
If the infant participant is reported to be experiencing or has had an MA-RTI from birth until Visit 3, the site should arrange a study visit as soon as possible 
and within 72 hours (preferable) or up to 10 days. Ideally, the RTI study visit will be conducted at the investigational study site; however, it is possible that 
the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit where the infant 
participant is residing. Note: Reporting MA-RTI events should commence 72 hours after the infant’s delivery.
b.
If the infant participant is reported to be experiencing or has had an MA-RTI associated with severe LRTI criteria or been hospitalized for an RTI from 
Visit 3 until the end of study participation, the site should arrange a RTI study (SRTI) visit as soon as possible and within 72 hours (preferable) or up to 
10 days ofthe MA-RTI visit. Ideally, assessment of these potential endpoint events (hospitalization due to RTI or severe MA-LRTI) will be conducted at 
the investigational study site; however, it is possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is 
hospitalized) or the site staff may visit where the infant participant is residing. Note: For nonsevere MA-RTIs, a telephone contact with the infant 
participants’ parent(s) or legal guardian(s) is acceptable to complete the follow-up assessments.
c.
Obtain case records, including details of hospitalization, ICU stays, use of oxygen, IV fluids usage, etc.
d.
The site staff/field worker will review and collect data related to any local NAAT testing results, if performed and available.
e.
The site staff/field worker will collect nasal swabs for confirmed MA- RTIs, including confirmed cases of hospitalizations due to an RTI and severe 
MA-LRTIs. In the event that restrictions prevent taking RTI study swabs because of an outbreak, pandemic situation, or natural disaster, the study nasal 
swab can be collected for processing at Pfizer’s central laboratory by the infant caregiver, during or within 10 days following an MA-RTI visit, or by the 
HCP assessing the infant during the MA-RTI visit (in addition to any samples obtained in the course of routine clinical care) as detailed in Section 8.11.7.1
and Section 8.11.8.
f.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV. This will be collected for 
all MA-RTI events reported.
g.
The investigator and site staff/field worker will ensure the active elicitation and collection of NDCMCs and SAEs through the end-of-study visit for the 
infant participant. From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected. An NDCMC is defined 
as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma). Note: A 
confirmed MA-RTI will not be captured as a safety event, unless the investigator or an appropriate designee deems it to be related to the investigational 
product or to have resulted in death.
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Protocol C3671008
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2. INTRODUCTION
Prevention of RSV disease in young infants is a significant unmet medical need globally.  
RSV is the leading cause of bronchiolitis and viral pneumonia in infants and can lead to fatal 
respiratory distress, especially in those with risk factors including premature infants with 
underlying cardiopulmonary disease, or in the absence of effective healthcare systems.1
However, most cases of RSV disease occur in healthy, full-term infants without risk factors.2
Worldwide, RSV kills approximately 118,200 children annually, with about half of those 
deaths occurring in infants under 6 months of age, and the majority of those occurring in 
resource-limited countries.3,4 In the United States, RSV is the leading cause of infant 
hospitalization, with more than 60,000 hospitalizations of children 12 months of age and 
younger annually.5,6  There is increasing evidence that the link between severe RSV disease 
in infancy and wheezing later in childhood may be causal.7,8  Like influenza, RSV infection 
follows a seasonal pattern, causing illness primarily in the cooler months of the year in 
temperate regions and during the wet season in tropical countries with seasonal rainfall.9  
Infection is essentially universal by the time children reach 2 years of age.10
Currently, there is neither specific treatment for RSV infection nor a vaccine to protect 
against RSV disease.  Treatment consists primarily of supportive care.  A prophylactic 
humanized monoclonal antibody, palivizumab (Synagis, AstraZeneca), targeting the RSV F 
glycoprotein is available for prevention of severe RSV disease in young infants at increased 
risk.11  Limitations of its use include its high cost12 and requirement of multiple monthly 
injections,13 and so it remains recommended for use only in very premature infants and 
others at increased risk of severe illness.6,14
Nevertheless, the protective effect of Synagis provides definitive proof of principle that 
serum neutralizing antibody directed against the F protein can provide clinically meaningful 
protection against RSV lower respiratory tract disease in young infants.15  Furthermore, it is 
well known that in other disease settings, antibodies transferred from mothers to their fetuses 
across the placenta can reduce infant disease early in life,16,17,18,19,20,21 suggesting that 
maternal immunization is a reasonable approach to RSV disease prevention among young 
infants.
There are 2 antigenic variants of RSV, namely, RSV subgroup A (RSV A) and RSV 
subgroup B (RSV B).  The RSV vaccine being investigated in this study is a bivalent vaccine 
composed of stable RSV prefusion F antigens representing the 2 subgroups to help ensure the 
broadest coverage against RSV illness.
RSVpreF is a prophylactic vaccine being developed to prevent medically attended
RSV-associated LRTI in infants by active immunization of pregnant women.
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2.1. Study Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given a global burden of disease in the millions of cases each year, maternal 
immunization offers an attractive strategy for infant disease prevention.  Both preclinical 
studies in animals and interim data from a Phase 1/2 study in healthy nonpregnant adults 
have demonstrated acceptable tolerability and safety of RSVpreF.  A robust immune 
response has also been observed in the population of the aforementioned trial, at 1 month 
after vaccination. The combined RSV A and B serum neutralization geometric mean titers 
(GMTs) have been shown to be 12 to 20 times higher than those with 100 μg/mL of
palivizumab, the concentration of the monoclonal antibody that is known to provide near to 
complete protection of high-risk infants from severe RSV disease.22,23 RSVpreF is currently 
under assessment in healthy pregnant women 18 through 49 years of age (Study C3671003, 
A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093).
The safety and tolerability of RSVpreF in pregnant adolescents has yet to be demonstrated. 
Vaccine-elicited immune responses with RSVpreF are expected to be similar in adolescents 
and women based on studies comparing maternal immunization with Tdap and HPV 
vaccination.24,25,26  Infants born to adolescent mothers are known to be at a higher risk of 
prematurity, an important risk factor for RSV disease.27,28 Therefore, pregnant adolescents 
(18 years of age) are an appropriate pediatric population for RSVpreF maternal 
immunization, providing insight toward the efficacy, safety, and tolerability of the vaccine.
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
RSV-associated LRTI in infants.
2.2. Background
RSV is an important cause of morbidity and mortality worldwide, with a substantial burden 
of disease borne by young infants.  Rates of severe RSV illness are highest in infants 
6 months of age, with a peak in hospitalization between 1 and 2 months of life, though the
highest case-fatality rates are observed in the neonatal period (<1 month).2 Infants born 
prematurely and those with underlying cardiac or pulmonary disease are at further increased 
risk of severe clinical disease due to RSV.  A 2017 retrospective case analysis that examined 
RSV mortality data from 23 countries demonstrates the global nature of the seriousness of 
RSV disease, with significant morbidity and mortality occurring in both lower- and 
middle-income countries (LMICs) and high-income countries.3,4
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No specific treatments for RSV exist, and available prophylactic measures (ie, RSV 
monoclonal antibody) are limited to use in only those infants at highest risk; additionally, in 
LMICs, use of available RSV prophylaxis is cost-prohibitive.  While active immunization 
against RSV in infants might be an option, multiple efforts, extending over half a century, to 
develop a safe and effective RSV vaccine to protect infants from disease have yielded little 
success.  The early peak of disease presents a further obstacle to an active vaccination 
strategy for infants.  Given these challenges, maternal immunization to protect infants early 
in life offers an attractive strategy for infant disease prevention.
The present RSV vaccine efforts were initiated in early 2014 based on a new scientific 
discovery (determination of the RSV prefusion F crystal structure)29 and a changing 
regulatory and policy environment that today supports the development of vaccines for 
maternal immunization to protect very young infants.  The trimeric RSV F surface 
glycoprotein in a prefusion conformation is now known to be the primary target of 
neutralizing antibodies and is the basis for the engineered antigens in Pfizer’s vaccine 
candidate.  Applying structure-guided vaccine design, Pfizer has developed a stabilized RSV 
prefusion F vaccine candidate.  The core hypothesis underlying Pfizer’s RSV vaccine 
development effort for prevention of infant disease is that vaccine antigens based on RSV 
prefusion F, when administered to pregnant women in the second or third trimester of 
pregnancy, will elicit sufficiently high neutralizing antibody titers that, when the antibodies
are actively transferred transplacentally to the fetus, will protect infants against RSV disease. 
The aim is for neutralizing antibody levels to be at sufficient levels such that infants will be 
protected from birth and possibly through their first RSV season. A post hoc analysis of the 
8 infants who had illness that met the Phase 3 case definition for MA-LRTI was performed. 
Observed efficacy (95% CI), against medically attended and medically attended severe infant 
LRTI due to RSV through 180 days, was 84.7% (21.5%, 97.6%) and 91.5% (-5.6%, 99.8%) 
respectively.
2.3. Benefit/Risk Assessment
RSVpreF is being evaluated in ongoing clinical studies.  Pfizer’s maternal immunization 
approach circumvents the risk of vaccine-mediated disease enhancement that was observed 
in the 1960s following direct immunization of RSV-naive infants with a formalin-inactivated 
RSV vaccine (FI-RSV).30  FI-RSV elicited a predominantly nonneutralizing antibody 
response and a Th2-biased cell-mediated response, both of which are considered potential 
contributing factors to disease enhancement.31  During preclinical studies, in a standard 
cotton rat infectious RSV challenge model, FI-RSV showed pathological signs of causing 
disease enhancement, and the current Pfizer vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease enhancement has not been reported to occur in 
RSV-experienced individuals after immunization with any RSV vaccine candidate.  Because 
pregnant women are universally RSV-experienced, they are not considered at risk for a 
disease-enhancing immune response to the vaccine that could exacerbate infection in 
themselves.  Enhanced disease has not been observed in infants born to mothers who
received prior investigational RSV vaccines; therefore, enhanced disease in infants is very
unlikely.  A previous study of maternal immunization with a Wyeth (later merged with 
Pfizer) investigational RSV vaccine (PFP-2) showed an acceptable safety profile, even 
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though this candidate contained a postfusion RSV F antigen that elicited a relatively weak 
RSV-neutralizing antibody response and a higher nonneutralizing RSV-binding antibody 
response in pregnant women.32  A recently completed Phase 3 maternal RSV trial (Novavax) 
with an RSV vaccine containing F not stabilized in the prefusion form, given to over 
4600 healthy pregnant volunteers, showed a similar safety profile in the RSV vaccine and 
placebo groups.33
Vaccination with the RSV prefusion F antigens elicit a higher ratio of neutralizing to 
nonneutralizing antibodies, more closely matching the profile in naturally exposed 
individuals.  The safety profile of RSVpreF observed to date is similar to that of prior RSV F 
subunit vaccines tested in RSV-experienced adults.
There are limited data on the global burden of maternal RSV infection, likely in part because 
of infrequent diagnostic testing. However, in one multisite study, RSV-associated disease in 
pregnancy was shown to result in prolonged hospitalization and an increased likelihood of 
preterm birth in women who tested RSV-positive.34 It is possible that vaccination may 
benefit the pregnant women who receive it. RTI in mothers who receive RSVpreF will be 
explored in this study.  The benefit of maternal vaccination is accrued to the infant by means 
of transplacental antibody transfer.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the investigator’s brochure (IB), which is the 
single reference safety document (SRSD) for this study.
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Protocol C3671008
Final Protocol Amendment 6, 01 June 2022
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Infant Participants
The study objectives and endpoints for infant participants employ the event definitions in 
Table 1.
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study Endpoints/Assessments
Study Definitions
Medically attended visit
Infant participant has been taken to or seen by a healthcare provider 
(eg, outpatient or inpatient visit, emergency room, urgent care, or home 
visit)
MA-RTI visit for infant 
participant
A medically attended visit AND 1 or more of the following RTI signs and 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any 
duration

Cough

Inability to feed for any duration because of respiratory symptoms

Apnea

Any other respiratory symptom of concern
RSV-positive testa

RSV RT-PCR–positive test result by Pfizer central laboratory
OR

RSV-positive test result by certified laboratory with NAAT for RSV
MA-RTI due to RSVb

An MA-RTI visit
AND

RSV-positive test result as described in Section 8.1.1.1
MA-LRTI due to any cause

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age], 
≥50 bpm for ≥2 months to <12 months of age, or ≥40 bpm for 
≥12 months to 24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age] or 
≥50 bpm for ≥2 to <12 months of age, or ≥40 bpm for ≥12 months to 
24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
AND

RSV-positive test result as described in Section 8.1.1.1
Hospitalized RTI due to RSVb
An RTI due to RSV that results in hospitalization
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Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study Endpoints/Assessments
Study Definitions
Severe MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥70 bpm for <2 months of age [<60 days of age], 
≥60 bpm for ≥2 months to <12 months of age, or ≥50 bpm for 
≥12 months to 24 months of age) OR

SpO2 <93% OR

High-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive) OR

ICU admission for >4 hours OR

Failure to respond/unconscious
AND

RSV-positive test result as described in Section 8.1.1.1
Protocol-defined primary 
endpoint

Any MA-LRTI or severe MA-LRTI due to RSV as determined by an 
EAC
Abbreviations: bpm = breaths per minute; EAC = endpoint adjudication committee; ICU = intensive care unit; 
MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically attended respiratory tract 
illness; NAAT = nucleic acid amplification technology; RR = respiratory rate; 
RSV = respiratory syncytial virus; RTI = respiratory tract illness; SpO2 = oxygen saturation.
a.
RSV-positive testing is defined as a positive RSV test (see Section 8.1.1.1) conducted on a sample 
obtained during the medically attended visit or within 10 days (where Day 1 is the day of the MA-RTI 
visit) as detailed in Section 8.11.7.
b.
The EAC will determine if the endpoint criteria have been met upon review of the site source 
documentation from the MA-RTI visit and RTI study visits, including all available RSV test results.
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Study Objectives – Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due 
to RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the EAC:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants born 
to maternal participants 
receiving 1 dose of 
investigational product, 
the percentage of 
participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

AEs from birth to 1 month of age.

SAEs and NDCMCs:
o
from birth through 6 months of 
age (first RSV season for all infant 
participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants enrolled 
during the first year of the study).
Secondary Efficacy Objectives –
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), defined 
as the relative risk reduction of 
the endpoint in the RSV 
vaccine group compared to the 
placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI:

occurring within 210 days after birth.

occurring within 240 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 270 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 270 days meets 
efficacy criteria.
Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI due to 
RSV.
RSV-positive MA-RTI:

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs from 
vaccination up to 730 days after birth.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 12 months of 
age.
MA-LRTIs due to RSV occurring 361 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI due 
to RSV in infants after 6 months 
of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV in infants after 6 months of 
age.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI in 
the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
To assess the impact of RSVpreF 
on RSV illness based on 
socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
To assess the effect of RSVpreF 
on healthcare utilization.
Univariate summaries of healthcare 
utilization variables, which may include the 
following: number and type of medical 
visits, length of hospital stay, requirement 
for mechanical ventilation, requirement for 
respiratory diagnostic procedures, 
requirement for IV fluids, requirement for 
prescriptions, and antibiotic use.
To describe the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI, MA-LRTI, 
and severe MA-LRTI in 
premature infants <37 weeks of 
age.
MA-RTI, MA-LRTI, and severe MA-LRTI
due to RSV occurring 0 to 730 days after 
birth.
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3.2. Maternal Participants
The study objectives and endpoints for maternal participants employ the event definitions in 
Table 2.
Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
Maternal medically attended visit
The maternal participant reports a visit with a healthcare 
provider (eg, outpatient or inpatient visit, emergency room, 
urgent care, or home visit)
MA-RTI visit maternal participant
A medically attended visit AND 1 or more of the following 
RTI signs and symptoms:

New or increased sore throat

New or increased cough

New or increased nasal congestion

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production

New or increased shortness of breath
Abbreviations: MA-RTI = medically attended respiratory tract illness; RTI = respiratory tract illness.
Study Objectives – Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimands
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery study 
visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum neutralizing 
titers and prefusion F IgG titers 
measured:

before vaccination.

at delivery.
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3.3. Protocol-Defined Efficacy Endpoints
All infant participants experiencing an MA-RTI will have an RTI study visit as detailed in
Section 8.1.  This protocol will use an independent EAC to determine whether certain 
investigator-reported events meet the definition of disease-related efficacy endpoints, using 
predefined endpoint criteria as summarized in Table 1. Members of this EAC will be blinded 
to the vaccine assignment to allow for unbiased assessments.
Recognizing that RSV disease is a dynamic illness, sites will be instructed to submit all 
available source documentation for adjudication from the MA-RTI visit and to record data 
from the worst day of illness in the electronic case report form (eCRF).  The EAC will 
determine if the endpoint criteria have been met upon review of the site source
documentation from the MA-RTI visit, including data collected at the RTI study visit, and all 
available RSV testing.  Further information about the EAC will be detailed in the 
adjudication charter, including specific descriptions of the scope of its responsibilities and 
the process and definitions to review and assess study endpoints.
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition and 
constitute a study endpoint will not be recorded as AEs.  For those AEs that are handled as 
disease-related efficacy endpoints, a data monitoring committee (DMC) will conduct 
unblinded reviews on a regular basis throughout the trial (see Data Monitoring Committee,
Section 9.5.1).
Nonendpoint events (eg, an event that is determined not to be an MA-RTI) must be evaluated 
for safety reporting as per the protocol requirements.  Any AE that is adjudicated by the EAC
to not meet any endpoint criteria will be reported back to the investigator site of incidence; 
the investigator at the site must evaluate the event for safety as described in Appendix 2 of 
this protocol.  If the event is classified as serious, the investigator’s SAE awareness date in 
this instance is identified as the date on which the investigator site receives the nonendpoint 
SAE back from the EAC.  Handling these SAEs in this manner will allow Pfizer to meet its 
sponsor reporting obligations to regulatory authorities upon receipt of such SAEs.
Any events that remain unadjudicated at the annual safety report cutoff date will not be 
included in the safety tables of the report.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
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This is an event-driven study with a target of at least 67 adjudicated (primary-endpoint) cases
of MA-LRTI due to RSV at 90 days (meeting the case definition in the per-protocol infant 
population described in the statistical analysis (Section 9.2). However, the final analysis will 
be performed at the end of the 2022 southern hemisphere RSV season, if fewer than 67 cases 
have occurred at that point. There is no specific case target for the additional primary 
endpoint of severe MA-LRTI. The total enrollment number of maternal participants may 
vary depending on the incidence rate of the primary endpoint in the infant participants, true 
underlying VE, and a potential early stop for efficacy or futility. In the event that efficacy in 
the infant population is demonstrated at an interim analysis, enrollment of maternal 
participants may continue in order to obtain safety evaluations in an adequate number of 
maternal and infant participants to support vaccine registration with national health 
authorities. Enrollment will be monitored to ensure even distribution of vaccination across 
gestational age between 24 0/7 and 36 0/7 weeks.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It was anticipated that approximately 
6900 mother-infant pairs would be needed to accumulate the original target of 
124 per-protocol cases prior to the global COVID-19 pandemic.  With the variable RSV 
season, the sample size is now expected to accrue at least 67 per-protocol cases. However,
with further variations in RSV seasonality, the sample size may need to be increased and 
enrollment could go up to 10,000 maternal participants based on the number of cases of 
RSV.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF for this study will be 
120 µg (60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.
Note: Maternal participants will include adolescent females who may be referred to as 
“minors.”  Information/assessments for minors may require parental/legal guardian 
awareness/approval per local regulations.
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term RTI 
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surveillance and safety oversight to address safety and the possibility of conferred enhanced 
protection (antibody persistence) during a second RSV season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. In addition, this study will use an 
E-DMC to monitor vaccine safety and efficacy and study futility.
4.1.1. Approximate Duration of Participation for Each Participant
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on GA at the time of vaccination and when the infant is 
actually born.
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
4.1.2. Approximate Number of Participants
Healthy pregnant women will be randomly assigned to a study intervention. It was 
anticipated that approximately 6900 mother-infant pairs would be needed to accumulate 
124 per-protocol cases as defined in Section 9.2 of the protocol prior to the global COVID-19 
pandemic.  With the variable RSV season, the sample size is now expected to accrue at least 
67 per-protocol cases. However, with further variations in RSV seasonality, the sample size 
may need to be increased and enrollment could go up to 10,000 maternal participants based 
on the number of cases of RSV.  Enrollment will be monitored to ensure that participants will 
be recruited from both the northern and southern hemispheres. Enrollment may vary 
depending on the incidence in the placebo group, the true underlying VE, the dropout rate, 
and a potential early stop for VE or futility.
4.2. Scientific Rationale for Study Design
Refer to Section 2.1.
4.3. Justification for Dose
The final dose and formulation of RSVpreF selected for use in this study is based on the 
safety and immunogenicity data from the ongoing C3671003 maternal immunization study
(A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093) and the first-in-human (FIH) study C3671001.
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The FIH study was designed to describe the safety, tolerability, and immunogenicity of 
6 RSVpreF candidates with bivalent formulations (RSV A and B) at 3 escalating dose levels 
of 60 µg (30 µg A and 30 µg B), 120 µg (60 µg A and 60 µg B), and 240 µg (120 µg A and 
120 µg B) of the RSV prefusion F antigen, with or without Al(OH)3, when administered 
alone or concomitantly with seasonal inactivated influenza vaccine.  The study utilizes a 
sentinel cohort (N=168; Phase 1) and an expanded cohort (N=1014; Phase 2).  Nonpregnant 
female and male study participants of 2 age groups, 18 through 49 years of age and 
50 through 85 years of age, were enrolled into both cohorts.  The age groups are being run in 
parallel.
An interim analysis of participants 18 through 49 years of age, including safety and 
tolerability (n=533) and immunogenicity (n=513) data up to 1 month after vaccination in the 
expanded cohort and additional immunogenicity data up to 3 months after vaccination in the 
sentinel cohort, has shown the RSVpreF candidate to be immunogenic and well tolerated.
Local reactions and systemic events were noted to be predominantly mild or moderate across 
all doses and formulations, which is consistent with the current safety profile. The safety 
results from this planned interim analysis of healthy male and nonpregnant female 
participants 18 through 49 years of age are consistent with those from the sentinel-cohort 
analysis and indicate that RSVpreF has an acceptable safety profile and is well tolerated.
The immunogenicity results showed that RSVpreF elicited neutralizing titer geometric mean 
fold rises (GMFRs) of 10 to 20, 1 month after vaccination, depending on the formulation. 
Similarly, across all dose levels, with and without Al(OH)3, RSVpreF elicited high 
1-month-postvaccination RSV A and RSV B neutralizing GMTs. Overall, RSVpreF elicited 
anti–prefusion F immunoglobulin G1 (IgG1) responses that paralleled the elicited 
RSV-neutralizing responses. The ratio of RSV 50% neutralizing antibody titer GMFRs to 
prefusion RSV F binding IgG1 titer GMFRs (calculated with combined data for subgroups A 
and B) for the sentinel and expanded 18 through 49 years of age cohorts combined ranged 
from 0.62 to 0.76. The IgG1 and neutralization responses were similar in antigen-level dose
response, in equivalence of RSV A titer GMFRs to RSV B titer GMFRs, and in a lack of 
effect of Al(OH)3.
Safety data for 403 mother/infant pairs, from maternal participants through 1 month after
maternal vaccination and for their infants from birth through the first month of life, in 
Study C3671003 provide further evidence of the safety of RSVpreF in maternal vaccine 
recipients, and initial evidence of the safety of maternal vaccination with RSVpreF for the 
infant. In maternal participants, solicited symptoms were generally mild to moderate in 
intensity and of short duration. Unsolicited AEs were consistent with anticipated events in 
this participant population and did not indicate any differences between RSVpreF and control 
recipients. No differences in pregnancy (eg, reports of preterm delivery or obstetric 
complications) and birth outcomes (eg, reports of respiratory distress at delivery or presence 
of congenital anomalies) were observed between RSVpreF and control recipients. No 
differences in the number or types of AEs reported were observed between infants born to 
mothers receiving RSVpreF and those receiving placebo in the first month of life.
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The high ratio of RSV-neutralizing antibody titer GMFRs to prefusion F–binding titer 
GMFRs elicited by Pfizer’s RSVpreF candidate indicates that most of the elicited antibody 
can neutralize the virus. It is assumed that this reflects the ability of the antibodies to prevent 
RSV disease in immunized participants and, in the case of maternal immunization, prevent 
disease in their infants.
The primary mechanism for protection of infants by the RSV maternal vaccine is 
neutralization of the virus by transplacentally transferred antibody, which is increased by 
immunization.  Maternal antibody decays exponentially in infants.  Therefore, it is 
anticipated that higher titers of transferred neutralizing antibodies will provide greater levels 
and durations of infant protection.  Results from the C3671001 FIH trial were used to 
determine the doses and formulations that are currently under investigation in the Phase 2b 
maternal immunization study: 120 µg or 240 µg of RSVpreF with or without Al(OH)3. 
These doses are expected to provide the greatest potential level of transplacental antibody 
transfer to infants and, therefore, the greatest potential benefit.  The dose and formulation of 
RSVpreF for the Phase 3 study was determined by the evaluation of the 1-month safety, 
tolerability, and immunogenicity results from the C3671003 maternal Phase 2b trial,
including infant RSV-neutralizing titers at birth.
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last visit.
The end of the study is defined as the date of the last visit of the last infant participant in the 
study. The study may also be terminated earlier for efficacy or futility as described in
Section 9.5.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1. Inclusion Criteria
5.1.1. Inclusion Criteria – Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply 
(refer to the investigator site file [ISF] for further eligibility details regarding region-specific 
timing of vaccination with respect to RSV seasonality and maternal gestational age at 
vaccination):
Note: In countries/locales where study procedures used to determine eligibility criteria 
(eg, ultrasound examination, human immunodeficiency virus [HIV] testing, syphilis testing) 
are not performed as part of routine prenatal care, they must be performed as part of this 
clinical trial and reviewed by the investigator or qualified designee within 28 days prior to 
randomization.  Maternal participants must provide informed consent prior to 
performing any procedures, including those that are being done exclusively to meet 
study eligibility criteria.
Note: Country-specific modifications associated with the study eligibility criteria are 
documented in Appendix 7, Appendix 8, and Appendix 9.
Age and Sex:
1. Healthy women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation 
on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are 
at no known increased risk for complications.
Note: GA must be based upon 1 of the following composite criteria based on timing and 
availability of data on the last menstrual period (LMP) and an ultrasound examination 
performed in the first or second trimester.35  The earliest ultrasound data available during 
the current pregnancy should be used. In countries where the routine practice is for the 
GA determination to be based upon the first trimester ultrasound examination alone, 
without the LMP, this routine practice will be accepted.
a.
First-trimester data available (data obtained at ≤13 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a first-trimester ultrasound examination.

If there is a discrepancy of 5 days between the LMP-determined GA and an 
ultrasound result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA 
should be determined using the first-trimester ultrasound result.

If there is a discrepancy of 7 days between the LMP-determined GA and an 
ultrasound result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, 
then the GA should be determined using the first-trimester ultrasound result.
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b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a second-trimester ultrasound result.

If there is a discrepancy of 7 days between the LMP-determined GA and the 
ultrasound result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of 10 days between the LMP-determined GA and the 
ultrasound result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of 14 days between the LMP-determined GA and the 
ultrasound result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
Type of Participant and Disease Characteristics:
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Receiving prenatal standard of care based on country requirements.
4. Had a fetal anomaly ultrasound examination performed at ≥18 weeks of pregnancy with 
no significant fetal abnormalities observed.
5. Determined by medical history, physical examination, and clinical judgment to be 
appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) 
surface antigen test during this pregnancy and prior to randomization (Visit 1).
7. Intention to deliver at a hospital or birthing facility where study procedures can be 
obtained.
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol OR
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If the maternal participant is illiterate, a thumb printed informed consent must be 
obtained, which must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process confirming that the maternal participant 
has been informed of all pertinent aspects of the study.
5.1.2. Inclusion Criteria – Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a 
thumb printed informed consent must have been obtained, which must have been signed 
and dated by an impartial witness who was present throughout the entire informed 
consent process confirming that the maternal participant/parent(s)/legal guardian(s) has 
been informed of all pertinent aspects of the study for herself (maternal participant) and 
her fetus/infant prior to taking part in the study.
Note: Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements.
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
5.2. Exclusion Criteria
5.2.1. Exclusion Criteria – Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not 
available, the BMI at the time of the first obstetric visit during the current pregnancy may 
be used.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any related 
vaccine.
4. Current pregnancy resulting from in vitro fertilization.  Participants known to have used 
clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are 
permitted.
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5. Current pregnancy complications or abnormalities at the time of consent that will 
increase the risk associated with the participation in and completion of the study, 
including but not limited to the following:

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.

Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated 
hypothyroidism.  This also includes disorders of glucose intolerance (eg, diabetes 
mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if 
uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the 
investigator’s judgment, that will increase the risk associated with the participation in and 
completion of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks’ gestation.

Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or significant congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the maternal 
or infant participant’s participation in, and completion of, the study or could preclude the 
evaluation of the maternal participant’s response (includes positive serologic testing for 
regional endemic conditions assessed during routine maternal care, as per local standards 
of care and obstetric recommendations).
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment.
9. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
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Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to 
consent and/or during study participation.
11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of 
systemic corticosteroids for >14 days within 28 days prior to study enrollment. 
Permitted treatments include the receipt of SARS-CoV-2 monoclonal antibodies, 
prednisone uses of <20 mg/day for ≤14 days and, inhaled/nebulized, intra-articular, 
intrabursal, or topical (skin or eyes) corticosteroids.
12. Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an 
exclusion criterion for the study when elicited in participant screening, though it may be 
considered illicit in some locales.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before 
investigational product administration, or planned receipt through delivery, with 
1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt 
during study participation. Note: Licensed COVID-19 vaccines or COVID-19 vaccines 
authorized for temporary, or emergency use will not be prohibited during the course of 
this study.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
5.2.2. Exclusion Criteria – Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
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5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and if no other exclusion criteria are met.  
The prevaccination blood draw and vaccination should take place on the same day. In the 
event that this is not possible, the prevaccination blood draw is also permissible within 7 days 
before the vaccination visit.

Current febrile illness (body temperature ≥38°C [≥100.4°F]) or other acute illness within 
48 hours before investigational product administration.

Diagnosed malaria within the last 7 days prior to investigational product administration.

Receipt of any inactivated vaccine (including licensed COVID-19 vaccines or COVID-19 
vaccines authorized for temporary or emergency use) within 14 days or any live vaccine 
within 28 days before investigational product administration.

If systemic corticosteroids (equivalent of ≥20 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical 
study but are not subsequently randomly assigned to investigational product. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs.
Maternal participants who do not meet the criteria for participation in this study (screen 
failure) may be rescreened.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
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6.1. Study Intervention(s) Administered
For this study, the investigational product(s) are RSVpreF and placebo (lyophile match).
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.  
The RSV drug product will be 120 µg of the RSV prefusion F antigen.  The drug product 
is supplied as a lyophilized white cake in a 2-mL glass vial, with a 13-mm lyophilization 
stopper, aluminum overseal, and flip-off cap. The drug product will be reconstituted by a 
diluent consisting of sterile water in a prefilled syringe (PFS). The lyophilized drug product 
contains excipients that, after reconstitution, will yield a solution as detailed in the IB.
The fill volume of the drug product vial and diluent PFS are designed such that the intended 
vaccine dose is delivered by injecting the entire contents of the syringe.
6.1.2. Placebo
Placebo will be a lyophile match to the vaccine, which will consist of excipients matched to 
those used in the RSVpreF vaccine formulation, minus the active ingredients.
The physical appearance of the reconstituted RSVpreF and placebo will be matched, and the 
study will be conducted in a double-blinded manner.
The fill volume of the placebo vial and diluent PFS is designed such that the intended 
placebo dose is delivered by injecting the entire contents of the syringe.
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
6.1.3. Administration
Maternal participants will receive 1 dose of investigational product at the vaccination visit 
(Day 1) in accordance with the study’s SoA.  The investigational product will be 
administered intramuscularly by injecting the entire contents of the syringe into the deltoid 
muscle, preferably of the nondominant arm, unless medically contraindicated, in which case 
the injection may be administered in the dominant arm. Investigational product
administration will be performed by appropriately designated study staff at the investigator 
site.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
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Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance.
Investigational product administration details will be recorded on the case report form (CRF).
6.1.4. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluent for the 
investigational product (RSV vaccine or placebo). The investigational product supplies are 
provided in a kit that contains the investigational product (RSV vaccine or placebo 
lyophilized powder in a vial), a prefilled syringe containing sterile water, and a vial adapter.
Instructions for medical device use are provided in the investigational product manual 
(IP manual).
Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the study personnel throughout the study.
Please refer to Section 8.3.9 for details.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention, as applicable for 
temperature-monitored shipments.
2. Only maternal participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking days must indicate the minimum and maximum 
temperature since previously documented for all site storage locations upon return to 
business.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  All study interventions will be 
accounted for using an investigational product accountability form/record.
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual.
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5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
6. Study interventions should be stored in their original containers and in accordance with 
the labels.
7. See the IP manual for storage conditions of the study intervention once reconstituted.
8. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use of 
the study intervention after the temperature excursion. Use of the study intervention prior 
to Pfizer approval will be considered a protocol deviation. Specific details regarding the 
definition of an excursion and information the site should report for each excursion will 
be provided to the site in the IP manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
6.2.1. Preparation and Dispensing
Refer to the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
Investigational product and placebo will be prepared by qualified site personnel according to 
the IP manual.  The investigational product will be administered only to maternal participants 
who are blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Blinding of Study Site Personnel
This study is a double-blinded study, as the physical appearance of RSVpreF and placebo 
will be matched. The maternal participant, her parent(s)/legal guardian (if a minor), 
investigator, study coordinator, and all site staff will be blinded.
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Please refer to the IP manual for further details.
6.3.2. Blinding of the Sponsor
The sponsor study team members will be blinded throughout the study to the vaccine 
assignments of all participants enrolled in the study.
Laboratory personnel performing the serology and virology assays will remain blinded to 
vaccine assigned/received throughout the study.
6.3.3. Allocation to Investigational Product
Allocation (randomization) of maternal participants to vaccine groups will proceed through 
the use of an interactive response technology (IRT) system (interactive Web-based response 
[IWR]).  The site personnel (study coordinator or specified designee) will be required to 
enter or select information including but not limited to the user’s identification (ID) and 
password, the protocol number, and the maternal participant number.  The site personnel will 
then be provided with a vaccine assignment, randomization number, and dispensable unit 
(DU) or container number as investigational product is being supplied via the IRT system.  
The IRT system will provide a confirmation report containing the maternal participant 
number, randomization number, and DU or container number assigned. The confirmation 
report must be stored in the site’s files.
Note: Maternal participants will be randomized to a vaccine group as described above.  The 
infants of the maternal participants will be manually assigned an infant participant number at 
birth.
Investigational product will be dispensed and administered at study Visit 1 summarized in 
the SoA.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Maternal participants will be assigned to receive investigational product according to the 
randomization scheme.  Investigators will remain blinded to the investigational product 
assigned to each maternal participant throughout the course of the study.
6.3.4. Breaking the Blind
The study will be maternal participant and investigator blinded.
At the initiation of the study, the investigator will be instructed on the method for breaking
the blind for an individual participant.  The method will be an electronic process.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the participant.  The 
investigators should make every attempt to contact a member of the sponsor’s study team 
prior to breaking the blind.  When the blinding code is broken, the reason must be fully
documented and entered on the CRF.
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The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal Participants

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study. Note: COVID-19 vaccines authorized for temporary, or emergency use will not be 
prohibited during the course of this study.

Receipt of blood/plasma products or Ig, from 60 days before investigational product 
administration, or planned receipt through delivery, with 1 exception, Rho(D) immune 
globulin (eg, RhoGAM), which can be given at any time.

Immunosuppressive therapy is prohibited during the course of the study.

Nonstudy vaccines may not be given concomitantly with the investigational product or 
within 7 days after investigational product administration (Day 1 to Day 7), except if 
medically necessary (eg, during an outbreak or pandemic situation).

Note: Licensed vaccines containing pertussis (including Tdap) may not be 
coadministered with the investigational product or given within 14 days after 
investigational product administration (Day 1 to Day 14), except if medically necessary 
(eg, during an outbreak- or pandemic-related situation).
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal Participants

Licensed vaccines (including influenza vaccine, tetanus toxoid, tetanus diphtheria 
vaccines, licensed COVID-19 vaccines, and COVID-19 vaccines authorized for 
temporary or emergency use) may be given during the study starting 7 days after
investigational product administration (Day 8), with the exception of licensed vaccines 
containing pertussis (including Tdap), which may be given starting 14 days after 
investigational product administration (Day 15) as detailed in Section 6.5.1.

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. Short-term systemic corticosteroid (equivalent of <20 mg/day of prednisone)
use for ≤14 days prior to the administration of investigational product is permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during participant participation in the 
study.
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6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following vaccinations and treatments for maternal participants would require reporting 
in the CRF during the study:

Details of any vaccinations given at any time during the pregnancy through the final 
study visit will be collected and recorded in the CRF.

Details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given to the maternal participant at any time during the 
pregnancy or during the study will be collected and recorded in the CRF.

Any prescribed medications taken to treat medically attended respiratory illnesses from 
enrollment until the final study visit will be recorded in the CRF.
Concomitant medications not meeting the criteria above will be assessed but not documented 
on the CRF.
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant Participants

Investigational vaccines, drugs, nutritional products, or medical devices are prohibited 
during the course of the study.
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant Participants

ONLY routine treatments, routine vaccinations, and routine procedures 
(eg, circumcision) are permitted at any time during the study, in accordance with national 
recommendations, medical standard of care, or accepted practice.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during infant participant participation in the study.

Local anesthetic may be applied to the site of the blood draw, as appropriate.
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications – Infant 
Participants
The following CRF reporting guidelines are applicable to treatments given to infant 
participants during the study:

Details of any Ig (including monoclonal antibodies [eg, Synagis] or immune globulin 
[eg, hepatitis B immune globulin (HBIG)]) or blood products (eg, whole blood, packed 
cells) given to the infant participant will be collected from the time of birth until the final 
study visit and recorded in the CRF.

Any prescribed medication taken to treat medically attended respiratory illnesses from 
the time of birth until the final visit.
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
Details of IV fluids given during an MA-RTI will be collected and recorded in the CRF.
6.6. Dose Modification
Dose modification is not applicable in this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Discontinuation of study intervention is not applicable in this study.
7.2. Participant Discontinuation/Withdrawal From the Study
A maternal participant may withdraw from the study at any time at her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. An infant participant may withdraw from the study at 
any time at the request of his or her parent(s) and/or legal guardian(s) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.
The participants, or, if appropriate, their parent(s) and/or legal guardian(s), should be
questioned regarding their reason for withdrawal. The participant will be permanently
discontinued from the study at that time.
If a maternal participant withdraws from the study, she may request destruction of any 
remaining samples taken and not tested, but data already generated from the samples will 
continue to be available and may be used to protect the integrity of existing analyses. If an 
infant participant is withdrawn from the study, his or her parent(s) and/or legal guardian(s) 
may request destruction of any remaining samples, but data already generated from the 
samples will continue to be available and may be used to protect the integrity of existing 
analyses. The investigator must document any such requests in the site study records and 
notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed, and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
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Participants who withdraw after randomization will not be replaced.
7.3. Withdrawal of Consent
Maternal participants and parent(s)/legal guardian(s) of infant participants born to maternal 
participants who request to withdraw consent from any further study contact or with persons 
previously authorized by the participant to provide this information should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible.  The withdrawal of consent should be explained in detail in the medical records by 
the investigator, as to whether the withdrawal is only from study procedures and/or 
postvaccination study follow-up. If the participant (maternal or infant) only withdraws from 
a study procedure, safety information should be completed until the end of the study, unless 
consent for further contact has been withdrawn.  In the event that vital status (whether the 
participant is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
The regulatory and ethical considerations for this study, including the informed consent 
process, are summarized in Section 10.1.1 and Section 10.1.3.
7.4. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant, or parent(s) and/or legal guardian(s) and
reschedule the missed visit as soon as possible and counsel the participant or parent(s) 
and/or legal guardian(s) on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or parent(s) and/or legal guardian(s) wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record.
o
Should the participant or parent(s) and/or legal guardian(s) continue to be 
unreachable, the participant will be considered to have withdrawn from the study.
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
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Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the maternal participant’s routine clinical 
management and obtained before signing of the ICD may be utilized for baseline 
purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA and protocol.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
8.1. Efficacy Assessments
8.1.1. Efficacy Assessments – Infant Participants
MA-RTIs in the infant participant will be identified from 72 hours after the infant’s delivery 
until the end of the infant’s participation in the study.  If the infant participant meets any RTI 
criteria listed below that require a visit by or a visit to an HCP (outpatient or inpatient visit, 
emergency room, urgent care, or scheduled home visit), an RTI study visit by the study staff 
will be required (see Section 8.11.7).
The RTI criteria are if the infant experiences 1 or more of the following respiratory signs or 
symptoms:
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
Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any duration

Cough

Inability to feed for any duration due to respiratory symptoms

Apnea

Any other respiratory symptom of concern
Evaluation of these MA-RTI events will be based on predefined clinical signs and symptoms 
and testing criteria (shown in Table 1) obtained at the medically attended visit with the 
healthcare provider and/or the study visit. These events will be assessed and confirmed to be 
contributing to the study endpoints by an independent EAC as per the protocol.
8.1.1.1. Midturbinate Nasal Swab Collection and Testing Requirements for Endpoint 
Confirmation – Infant Participants
Midturbinate nasal swabs will be collected for RSV analyses from infant participants at each 
RTI study visit during the RSV surveillance period from birth until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). The swabs
will be sent to Pfizer for centralized reverse transcription–polymerase chain reaction 
(RT-PCR) testing.
RSV testing performed locally as part of routine care will be considered valid when analyzed 
under the following conditions:

Nucleic acid amplification technology (NAAT)-based test result positive for RSV was 
obtained using a Food and Drug Administration (FDA)-cleared assay.
AND

NAAT-based test result was obtained in a laboratory that is currently Clinical Laboratory 
Improvement Amendments (CLIA)-certified or has the equivalent US 
certification/accreditation (eg, College of American Pathologists [CAP]) or the equivalent 
ex-US certification as outlined in the adjudication charter.
Note: Rapid antigen-based test results will not be considered for endpoint assessment.
Study samples should be collected as close to the medical visit as possible and preferably 
within 72 hours of the MA-RTI visit. Study samples positive for RSV by RT-PCR as 
defined above will count toward the endpoint definition when collected for up to 10 days 
after the MA-RTI, where Day 1 is the day of the MA-RTI visit. These results will be used 
for MA-RTI endpoint definition and confirmation as detailed in Table 1.
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8.1.1.2. Events for Adjudication and Submission Guidance – Infant Participants
To maintain scientific integrity, this protocol will use an EAC for the adjudication of all 
efficacy endpoints as summarized below.  The EAC will remain blinded to the maternal 
participants’ vaccine assignments, and the EAC’s assessment of these events will represent 
the final confirmed endpoint classification of the event.
The efficacy-related events for adjudication include all MA-RTI events. The study 
definitions for endpoint events and the MA-RTI adjudication criteria for the EAC, including 
roles and responsibilities, are specified in the endpoint adjudication committee charter 
(EACC).
The identification of an MA-RTI will be made by the investigational site and communicated 
to Pfizer or its designee. However, these MA-RTI events may also be identified by Pfizer or 
its designee during the review of clinical data listings or by site monitors during routine 
monitoring of the infant participants’ study records. Pfizer or its designee will notify the 
investigational site of any events identified during this process.
The EAC is responsible for adjudicating whether MA-RTI events fulfill the protocol-defined 
clinical criteria as a primary endpoint, whether the event was due to RSV based on 
confirmatory testing, and the severity of the illness (eg, MA-RTI, MA-LRTI, or severe 
MA-LRTI).  The EAC will adjudicate all RSV-positive MA-RTI cases through the active 
follow-up period including all cases occurring up to 180 days after birth. The EAC will 
adjudicate severe manifestations of RSV: all RSV-associated cases of hospitalization and 
severe MA-LRTI. All deaths during the study are to be reported to Pfizer Safety upon 
awareness.
The Pfizer study team or designee will provide a listing of specific documents needed to 
support endpoint adjudication by the EAC. These documents will be detailed in the EACC
and the ISF.  Obtaining and submitting the documentation, including results of local testing 
for RSV, will be the responsibility of the investigational site. Documentation will vary based 
on the potential endpoint requiring adjudication and may include (but not be limited to) 
emergency room visit records, hospital discharge summaries, clinic and/or progress notes, 
diagnostic tests, pathology reports, autopsy reports, and death certificate information, as 
applicable.
Pfizer may request that additional cases of interest be reported to the committee in addition to 
those listed above, including cases in which RSV testing is indeterminant or otherwise 
unclear. Cases that are determined to be RSV positive using non–NAAT-based clinical 
testing can be adjudicated, explored, and summarized descriptively.
8.1.2. Exploratory Efficacy Assessments – Maternal Participants
An MA-RTI will be identified from vaccination until the end of the study and will contribute 
to an exploratory endpoint for maternal participants.  The definition and assessment criteria 
as described in Section 8.10.6 include a visit by or to a healthcare provider (outpatient or 
inpatient visit, emergency room, urgent care, or home visit) for any symptoms in the RTI 
criteria as detailed in Table 2.
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The maternal participant or her parent(s)/legal guardian (if a minor) should contact the study 
staff immediately but no later than the next scheduled visit to report RTI signs and symptoms 
for which she sought medical attention. The procedures as detailed in Section 1.2.3.1 and 
Section 8.10.6 will be required to capture the event in the CRF.
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal and Infant 
Participants
Infant MA-RTI events that are consistent with the clinical and endpoint definitions for infant 
participants should not be recorded as AEs. These data will be captured as efficacy 
assessment data only, as these are expected endpoints.
For maternal participants, MA-RTI events that are consistent with the clinical and endpoint 
definition will be captured as detailed in Section 8.1.2 and will not be recorded as AEs.
Any event that the investigator has judged to have a causal relationship with the 
investigational product or to have resulted in death MUST be reported to Pfizer Safety as 
described in Appendix 2, even if that event is a component of an endpoint.
8.1.4. Immunogenicity Assessments
8.1.4.1. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be approximately 30 mL (~15 mL/visit).
8.1.4.2. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical 
Consideration for Clinical Trials Performed in Children.36
All infants will have a cord blood sample collected at birth. The cord blood is collected from 
the umbilical cord vein attached to the placenta after the umbilical cord has been clamped 
and cut. Blood should be collected as soon as feasible after birth to minimize coagulation 
and maximize volume. The total volume of cord blood to be collected for antibody 
assessment in this study will be 10 mL.
If cord blood is unavailable, a blood sample may be collected from the infant participant up 
to 7 days after birth but preferably within 24 hours after birth.  The infant’s weight must 
be used to determine the volume of blood that can be collected (see Table 3).
A blood sample will be collected from the infant participant only if a cord sample is not
obtained. In the event that a sample is collected, the volume of blood will vary depending on 
the infant’s weight.
The maximum volume of blood collected from the infant in the absence of cord blood will be 
no more than 5 mL.
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Table 3.
Guideline for Infant Blood Draw, If Cord Blood Sample Was Not 
Obtained
Body Weight (in kg)
Approximate Volume of Blood (in mL)
to Be Collected
1.3
No blood draw
1.3 to ≤2.4
1.0
>2.4 to ≤3.7
2.0
>3.7 to ≤4.9
3.0
>4.9 to ≤6.2
4.0
>6.2
5.0
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant Participants
Maternal sera (prevaccination/time of delivery) and infant cord blood collected will be 
assayed for RSV A and RSV B serum neutralizing titers and anti-RSV prefusion F IgG 
levels. Maternal sera collected may be tested for Ig levels against nonvaccine RSV antigens
to assess natural RSV exposure.
RSV A and RSV B serum neutralizing titers will be determined and reported as the 
neutralizing titer. IgG levels will be determined against both RSV A and RSV B prefusion F 
antigens in a direct-binding Luminex immunoassay (dLIA) and reported as an 
anti–prefusion F IgG level.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development – Maternal and Infant Participants
Samples remaining after completion of the planned assays from blood draws or infant 
respiratory nasal swab specimens taken throughout the study may be used for additional 
vaccine and infectious disease related research. Samples may also be used for assay 
development, standardization, qualification, and validation.  This work is critical in the 
development, qualification, and validation of serological assays and is required by regulatory 
authorities for their use in the licensure of a vaccine.
8.1.4.5. Respiratory Pathogens – Infant Participants
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI
visit during the RSV surveillance period from birth until Visit 3, and for all hospitalizations 
due to an RTI and severe cases of MA-LRTI during the RTI surveillance period from 
Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1).
Samples will be analyzed for RSV A, RSV B, and other respiratory pathogens by polymerase 
chain reaction (PCR)-based assays at a central laboratory. Additional exploratory analyses 
may also be performed.
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Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.6. Biological Samples – Maternal and Infant Participants
Samples will be used only for scientific research.  Each sample will be labeled with a code so 
that the laboratory personnel testing the samples will not know the maternal or infant
participant’s identity.  Samples that remain after performing assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.  If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No sequencing of the maternal or infant participant’s DNA will be performed.
The maternal participant may request that her (or her infant’s) samples, if still identifiable, be 
destroyed at any time; however, any data already collected from those samples will still be 
used for this research.  The biological samples may be shared with other researchers as long 
as confidentiality is maintained, and no testing of the maternal and infant participant’s DNA 
is performed.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
Safety parameters will be assessed as described in the SoA and below for both maternal and 
infant participants.
8.2.1. Participant Electronic Diary – Maternal Participants
All maternal participants vaccinated in the study will be observed for at least 30 minutes after 
investigational product administration for any acute reactions. For all maternal participants, 
prespecified local reactions and systemic events will be collected for 7 days after vaccination.
Maternal participants will be required to use an electronic diary (e-diary), installed on a 
provisioned device or as an application on a personal device, and will be asked to monitor 
and record local reactions, systemic events, and temperature each evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  Prior 
to vaccination, a baseline assessment of prespecified systemic events will be recorded in the 
e-diary.
The e-diary allows recording of these assessments only within a fixed time window each day, 
thus providing the accurate representation of the maternal participant’s experience at that 
time.
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If the maternal participant is illiterate, a study staff/field worker may visit the maternal 
participant in her home or contact her via phone daily after vaccination to assess and record 
local reactions, systemic events, and temperature each day (beginning in the morning) for 
6 days following vaccination (Day 2 through Day 7). Maternal participants or her 
parent(s)/legal guardian (if a minor) may call the site and report additional local reactions and 
systemic events at any time during the Day 1 to Day 7 reporting period.  The study staff/field 
worker will be required to record these data on a provisioned device or an application on a 
personal device, thus providing the accurate representation of the maternal participant’s 
experience at that time.  For events persisting at Day 7 and use of antipyretic medication 
continuing at Day 7, the field worker will continue to visit the participant and record 
information until resolution.
Data on local reactions, systemic events, and temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via an internet-based 
portal.  At intervals agreed to by the vendor and Pfizer, these data will be transferred 
electronically to Pfizer for analysis and reporting.  These data do not need to be recorded by 
the investigator in the CRF, except the following conditions:

If a maternal participant withdraws because of prompted events recorded in the e-diary, 
the event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF.
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate maternal participant compliance and as part of the 
ongoing safety review. These prospectively collected occurrences of local reactions and 
systemic events are graded as described in Section 8.2.1.1 and Section 8.2.1.2.
8.2.1.1. Local Reactions – Maternal Participants
Following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), the 
maternal participants or her parent(s)/legal guardian (if a minor)/study staff member/field 
worker will be asked to assess redness, swelling, and pain at the injection site and to record 
the symptoms in the e-diary or appropriate device, in the evening or daily based on local 
practice.
Redness and swelling will be measured by the maternal participant/study staff/field worker 
and recorded in measuring device units (range: 1 to 20 and 21+) and then categorized during 
analysis as mild, moderate, or severe based on the grading scale in Table 4. Measuring 
device units can be converted to centimeters according to the following scale: 1 measuring 
device unit = 0.5 cm.
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A maternal participant with severe redness, swelling, or pain at the injection site will be 
prompted to contact the investigator to perform an unscheduled visit to assess the reaction or 
will be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate.  In the event that the maternal participant
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor).
Only an investigator or a qualified designee is able to classify a maternal participant’s local 
reaction as Grade 4, after clinical evaluation of the maternal participant or documentation 
from another medically qualified source (eg, emergency room or hospital record) or, in the 
case of pain at the injection site only, contact with the maternal participant.  If a maternal 
participant experiences a Grade 4 local reaction, the investigator must immediately notify 
the sponsor.  A Grade 4 reaction will be collected as an AE on the CRF.  The event will be 
graded using the AE intensity grading scale (Section 10.2.4).
The site staff/field worker will educate the maternal participant and her parent(s)/legal 
guardian (if a minor) regarding signs and symptoms that would prompt site contact.
If a local reaction persists beyond the end of the e-diary period, the maternal participant or 
her parent(s)/legal guardian (if a minor) will be requested to report that information and/or 
any new AEs that develop to the investigator, or the study staff/field worker will continue to 
call or visit the maternal participant to assess and record the information until resolution, as 
per local practice. The investigator will enter this additional information in the maternal 
participant’s source notes and CRF.
Table 4.
Grading Scale for Local Reactions
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis
Pain (at the 
injection site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a maternal participant’s local reaction as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
contact with the maternal participant or her parent(s)/legal guardian (if a minor).  Grade 4 local reactions 
will be collected on the AE case report form and assessed by the investigator using the AE intensity 
grading scale as detailed in Section 10.2.4.
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8.2.1.2. Systemic Events – Maternal Participants
Prior to vaccination on Day 1, a baseline assessment of fatigue, headache, vomiting, 
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e-diary. Following 
vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), maternal 
participants or their parent(s)/legal guardian (if a minor) will be asked to assess fatigue, 
headache, vomiting, nausea, diarrhea, muscle pain, and joint pain and to record the symptoms 
in the e-diary in the evening or, based on local practice in certain countries/locales, a study 
staff member/field worker will call or visit maternal participants daily after vaccination to 
assess the presence of systemic events each day (beginning in the morning) for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  The 
study staff member/field worker will record the symptoms in the e-diary daily. The 
symptoms will be assessed by the maternal participant according to the grading scale in 
Table 5.  Maternal participants and their parent(s)/legal guardian (if a minor) will also be 
instructed to contact site staff if they visit the emergency room or are hospitalized for severe 
fatigue, headache, vomiting, nausea, diarrhea, muscle pain, or joint pain within 7 days after 
vaccination. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor). The study staff/field worker may also contact the 
maternal participant or her parent(s)/legal guardian (if a minor) to obtain additional 
information on events entered into the e-diary.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic 
event as Grade 4, after clinical evaluation of the maternal participant or documentation from 
another medically qualified source (eg, emergency room or hospital record) or contact with 
the maternal participant.  If a maternal participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.  Grade 4 reactions will be collected as an 
AE on the CRF.  The event will be graded using the AE intensity grading scale 
(Section 10.2.4).
Further, if a systemic event persists beyond the end of the e-diary period, the maternal 
participant or her parent(s)/legal guardian (if a minor) will be requested to report that 
information and/or any new AEs that develop to the investigator, or the study staff/field 
worker will continue to call or visit the maternal participant to assess and record the 
information until resolution, as per local practice. The investigator will enter this additional 
information in the maternal participant’s source notes and CRF.
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Table 5.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness in 
diaries)
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Headache
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Vomiting
1 to 2 times in 24 hours
>2 times
in 24 hours
Requires 
intravenous 
hydration
Emergency room 
visit
or hospitalization 
for severe vomiting
Nausea
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe nausea
Diarrhea
2 to 3 loose stools
in 24 hours
4 to 5 loose stools
in 24 hours
6 or more loose 
stools
in 24 hours
Emergency room 
visit
or hospitalization 
for severe diarrhea
Muscle pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe muscle pain
Joint pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe joint pain
a.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic event as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the maternal participant or her 
parent(s)/legal guardian (if a minor).  Grade 4 systemic reactions will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.1.3. Temperature – Maternal Participants
A digital thermometer will be given to the maternal participant with instructions on how to 
measure oral temperature at home in degrees Celsius.  Temperature will be collected in the 
evening for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination) and at any time during the 7 days following vaccination that fever is suspected. 
Similarly, based on local practice in certain countries/locales, the study staff/field worker will 
call or visit maternal participants daily for 6 days after vaccination (Day 2 through Day 7, 
where Day 1 is the day of vaccination) to collect the temperature.
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Fever is defined as an oral temperature of ≥38.0°C (≥100.4°F). The highest temperature for 
each day will be recorded in the e-diary, where possible. In certain countries/locales, if a 
temperature of ≥38.0°C (≥100.4°F) is recorded for a maternal participant during the 
collection of diary events after vaccination, the study staff/field worker will perform a rapid 
test for malaria as per local practice.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature less than 38.0°C [100.4°F]) in order to 
collect a stop date in the CRF.
A maternal participant with a fever >38.9°C (>102.0°F) will be prompted to contact the 
investigator. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as applicable. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor).  The investigator or qualified designee will assess 
the fever and perform an unscheduled visit as appropriate.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as 
Grade 4, after clinical evaluation of the maternal participant, documentation from another
medically qualified source (eg, emergency room or hospital record), or contact with the 
maternal participant or her parent(s)/legal guardian (if a minor).  Grade 4 fevers will be 
collected on the AE CRF and assessed by the investigator using the AE intensity grading 
scale as detailed in Section 10.2.4.
Temperature will be measured and recorded to 1 decimal place and then categorized during 
analysis as mild, moderate, or severe based on the intensity grading scale provided in
Table 6.
Table 6.
Ranges for Fever
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fever
≥38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°C
a.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as Grade 4, 
after clinical evaluation of the maternal participant, documentation from another medically qualified 
source (eg, emergency room or hospital record), or contact with the maternal participant or her 
parent(s)/legal guardian (if a minor).  Grade 4 fevers will be collected on the AE case report form and 
assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant Participants
There are no protocol-required laboratory assessments.
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8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 4.  Device deficiencies are covered in Section 8.3.9.
AEs will be reported by the maternal participant/parent(s)/legal guardian(s).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7).
Each maternal participant or her parent(s)/legal guardian (if a minor) and parent/legal 
guardian/legally authorized representative of an infant participant will be questioned about 
the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
Maternal Participants
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each maternal participant including her fetus begins from the time the maternal 
participant and her parent(s)/legal guardian (if a minor) provides informed consent, which is 
obtained before participation in the study (ie, before undergoing any study-related procedure 
and/or receiving investigational product), through and including a minimum of 28 calendar 
days after the last administration of the investigational product.
In this study, the investigator and site staff will ensure the active elicitation and collection of 
safety events as detailed below:

The active collection period for nonserious AEs begins once informed consent has been 
provided and continues through a minimum of 28 calendar days after vaccination.

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

In addition, AEs occurring up to 48 hours after blood draws that are related to study 
procedures must be reported in the CRF.
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
Details of any MA-RTI will not be collected as AEs/SAEs from informed consent until 
the maternal participant completes the study, unless the investigator or an appropriate 
designee deems the event to be possibly related to the investigational product or to have
resulted in death as detailed in Section 8.1.2 and Section 8.1.3.
For maternal participants who are screen failures, the active collection period ends when 
screen failure status is determined.
Infant Participants
For the infant participant, the time period for actively eliciting and collecting safety events is 
detailed below:

The active collection period for nonserious AEs begins at birth and continues through and 
including a minimum of 28 calendar days after birth.

The active collection period for NDCMCs and SAEs begins at birth and continues 
through the last study visit.
o
Details of any MA-RTI will not be collected as AEs/SAEs from 72 hours after 
birth until the infant participant completes the study, unless the investigator or an 
appropriate designee deems the event to be possibly related to the investigational 
product or if the event resulted in death. See Section 8.1 for the reporting 
procedures for efficacy-related endpoints. Note: Details of the MA-RTI visit 
should be recorded in the eCRF.

In addition, AEs occurring up to 48 hours after blood draws or nasal swabs that are 
related to study procedures must be reported in the CRF.
For Both Maternal and Infant Participants
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For maternal participants, and parent(s)/legal guardian(s) of infant participants born to 
maternal participants, who withdraw from the study and withdraw consent for the collection 
of future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form.
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Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the Vaccine SAE Reporting Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the Vaccine SAE Reporting Form, immediately upon awareness and under no 
circumstances should this exceed 24 hours.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy; 
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those that occur within 1 month after birth; or congenital 
anomaly* [in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal 
death]), the investigator should follow the procedures for reporting SAEs.  In addition, infant 
deaths after 1 month of age should be reported as SAEs.
Further follow-up may be requested by the sponsor and will be handled on a case-by-case 
basis (eg, follow-up on preterm infants to identify developmental delays).
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
The same is applied for those SAEs after the active collection period has ended, should they 
occur to the fetus.  In addition, infant deaths that occur after 12 months of age should be 
reported as SAEs when the investigator believes the SAE or death has at least a reasonable 
possibility of being related to investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.37
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All AEs/SAEs occurring in a participant during the active collection period, which begins 
after obtaining informed consent as described in Section 8.3.1, will be recorded on the AE 
section of the CRF.
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The investigator is to record on the CRF all directly observed, and all spontaneously reported 
AEs and SAEs reported by the participant, or her parent(s)/legal guardian (if a minor) and
parent(s)/legal guardian(s) of infant participants born to maternal participants.
The investigator obtains general information on the pregnancy and its outcome for all study 
participants.  The investigator will follow the pregnancy until completion (or until pregnancy 
termination).  In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth.  In the event of a termination, the reason(s) for termination should be 
specified and, if clinically possible, the structural integrity of the terminated fetus should be 
assessed by gross visual inspection (unless preprocedure test findings are conclusive for a 
congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, stillbirth, neonatal death,
defined as those deaths that occur within 1 month after birth; or congenital anomaly* [in a 
live-born baby, a stillbirth, or a neonatal death]), the investigator should record this 
information in the CRF.  In addition, infant deaths after 1 month of age should be recorded in 
the CRF as SAEs.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.37
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.4).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety.
Further information on follow-up procedures is given in Appendix 2.
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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
Potential efficacy endpoints on this study as defined in Section 8.1 will be excluded from the 
standard SAE reporting process unless deemed possibly related to investigational product.
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the 
Investigational Product
8.3.5.1. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Scenarios of exposure during breastfeeding for infants not delivered during the study must be 
reported, irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours 
of the investigator’s awareness, using the Vaccine SAE Reporting Form.  An 
exposure-during-breastfeeding report is not created when a Pfizer drug specifically approved 
for use in breastfeeding women (eg, vitamins) is administered in accord with authorized use.  
However, if the infant experiences an SAE associated with such a drug’s administration, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.2. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
investigational product, which may or may not lead to the occurrence of an AE. Such 
persons may include HCPs, family members, and other roles that are involved in the trial 
participant’s care.
Note: This does NOT apply to maternal participants enrolled in this trial.
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In addition, the scenarios below describe environmental exposures that could lead to an 
exposure during pregnancy (EDP):

A female becomes or is found to be pregnant, having been exposed (eg, because of 
environmental exposure) to the investigational product; or the female becomes or is 
found to be pregnant after being exposed to the investigational product;

A male has been exposed (eg, because of environmental exposure) to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the Vaccine SAE Reporting Form and the Exposure During Pregnancy 
Supplemental Form, as applicable, regardless of whether there is an associated SAE.  In the 
event of an EDP, the information submitted should include the anticipated date of delivery.  
Since the information does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the ISF.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
are as follows:

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.
8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
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8.3.8. Adverse Events of Special Interest
This section provides information on adverse events of special interest (AESIs) that may be 
detected during the study.
For infant participants:

Preterm birth (born at <37 weeks’ gestation)

Birth weight 1001 to 2500 g

Developmental delay*

Positive viral (PCR or antigen-based) testing for SARS-CoV-2, when not reported 
during a MA-RTI visit, should be reported as SARS-CoV-2 test positive
The following AESIs are to be reported as SAEs:

Extremely preterm birth (<28 weeks)

Extremely low birth weight (≤1000 g)
For maternal participants:

Preterm delivery

Positive viral (PCR or antigen-based) testing for SARS-CoV-2, when not reported 
during a MA-RTI visit, should be reported as SARS-CoV-2 test positive
All AESIs must be reported as an AE or SAE following the procedures described in
Section 8.3.1 through Section 8.3.4 except the active collection period for AESIs is from the 
signing of the ICD until the end of the study for maternal participants and from birth until the 
end of the study for infant participants.
Notes: An AESI that is recorded as an SAE must be reported using the Vaccine SAE 
Reporting Form.
*Developmental delay is to be assessed by clinical expertise using local guidelines for 
standard of care. Events identified as both an AESI and an NDCMC should be reported as an 
AESI in the CRF.
8.3.8.1. Lack of Efficacy
This section is not applicable for this study, as efficacy is yet to be demonstrated in the study 
population.
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8.3.9. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 4.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 2 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 4.
8.3.9.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  Follow-up applies to all participants, including 
those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
Information will be provided to the sponsor as described in the IP manual.
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
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8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration by an incorrect route;

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
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In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any additional dose of investigational product will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose in the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
No interruptions or dose modifications will be made in this study.
8.5. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
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8.9. Health Economics
Health economics will be evaluated in exploratory analyses assessing vaccine impact on 
healthcare resource utilization parameters evaluated during study visits, which may include 
the following: number and type of medical visits, length of hospital stay, requirement for 
mechanical ventilation, requirement for respiratory diagnostic procedures, requirement for 
IV fluids, requirement for prescriptions, and antibiotic use.
8.10. Procedures – Maternal Participants
8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to Vaccination to Day 1 –
Visit 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant or their parent(s)/legal 
guardian (if a minor). Each signature on the ICD must be personally dated by the signatory.
Maternal participants who might be illiterate must thumbprint the ICD and it must be signed 
and dated by an impartial witness who was present throughout the entire informed consent 
process before performing any study-related procedures.
The investigator or his or her designee will also sign and date the ICD.  A copy of the 
signed/thumbprinted and dated ICD must be given to the maternal participant and her 
parent(s)/legal guardian (if a minor).  The source data must reflect that the informed 
consent was obtained before participation in the study.
If the maternal participant is found ineligible for the study based on a full assessment of 
inclusion and exclusion criteria, the investigator may advise the participant and her 
parent(s)/legal guardian (if a minor), either by telephone or face to face, that the participant 
will be excluded from further participation in the study, as defined in Section 5.4.  All 
eligible maternal participants will proceed to complete the vaccination visit.
Standard-of-care procedures performed prior to informed consent can be considered for use 
in the study provided they follow guidance around the timing of procedures stipulated in the 
protocol.
In countries/locales where procedures to confirm maternal participant eligibility for
this clinical trial are not routinely performed, the procedures must be obtained and 
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.
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The following procedures will be performed:

Obtain written informed consent, and assent if appropriate, from the maternal participant
before performing any study-specific procedures. If the maternal participant is illiterate,
she must thumbprint the ICD and it must be signed and dated by an impartial witness 
who was present throughout the entire informed consent process.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity).  The date of birth will be 
collected to critically evaluate the immune response and safety profile by age.

Obtain and record current/former alcohol, tobacco, marijuana, or any illicit drug usage.

Obtain and record any medical, surgical, and obstetric history of clinical significance 
including history from prior and current pregnancy(ies).

Record the LMP and estimated delivery date (EDD).

Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.

Record the prepregnancy BMI in the source documentation. If the prepregnancy BMI is 
not available, record the BMI at the time of the first obstetric visit during the current 
pregnancy.

Perform targeted physical examination evaluating/noting any clinically significant 
abnormalities within the following body systems:
o
Mandatory - general appearance; heart; lungs; abdomen.
o
Discretionary - skin; head, eyes, ears, nose, and throat; musculoskeletal; extremities; 
neurological; lymph nodes.
Note: Significant medical and surgical history and abnormal observations from the 
physical examination will be documented and recorded in the CRF.

Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement.
o
Where an obstetric ultrasound examination is not performed at ≥18 weeks of 
pregnancy as part of prenatal standard of care, perform an ultrasound examination.
o
Note: Physical or obstetric examinations performed as standard of care may be 
admissible if performed within 7 days prior to the vaccination visit.
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
Obtain details of any Ig (including monoclonal antibodies or immune globulin [Rho(D) 
immune globulin, eg, RhoGAM]) or blood products (eg, whole blood, packed cells) given 
at any time during the current pregnancy.

Obtain details of any nonstudy vaccinations given at any time during the current 
pregnancy.

Obtain details of syphilis, HIV, and HBV status.
o
Note: Only participants with a documented negative syphilis test result and negative 
HIV antibody and HBV surface antigen test results obtained during the current 
pregnancy are eligible for randomization.
o
If not performed as standard of care, assessment should be performed as part of the 
study, locally, and vaccination of maternal participant should be deferred until the 
results are available and confirmed to be negative within 28 days prior to study 
randomization.

Ensure and document that all the inclusion criteria and none of the exclusion 
criteria are met.

Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.2.3.

Issue the maternal participant an e-diary and provide instructions on its completion
(if applicable). Note: eDiary completion instructions may be provided to her 
parent(s)/legal guardian (if a minor).

Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures and provide instructions on their use to the maternal 
participant and her parent(s)/legal guardian (if a minor).

On the day of and prior to vaccination, ask the maternal participant to capture the 
baseline systemic event measurements in her e-diary or the site staff will capture the 
baseline systemic event measurements in the provisioned device (if applicable for 
illiterate participants).

Prior to vaccination, collect a blood sample of approximately 15 mL for serologic 
assessments (prevaccination blood collection should take place on the same day or within 
7 days before the vaccination visit).

Obtain the maternal participant’s randomization number and investigational product kit 
number using the IRT system. Refer to the IRT manual for further instructions on this 
process.
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
Qualified site staff member(s) will administer a single-vial dose of investigational 
product into the deltoid muscle of the (preferably) nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
Please refer to the IP manual for further instruction on this procedure.

Site staff must observe the maternal participant for any acute reactions for at least 
30 minutes after investigational product administration.

Record any acute reactions in the maternal participant’s source documents, on the AE 
page of the CRF, and on the Vaccine SAE Reporting Form as applicable.

Ask the maternal participant to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination, OR explain to the maternal participant that a study staff 
member/field worker will call or visit her every day from Day 2 to Day 7 after 
vaccination (where Day 1 is the day of vaccination) to collect or take her temperature and 
record systemic events, acute local reactions, and use of antipyretic medication in a diary
(if applicable).

Ask the maternal participant or her parent(s)/legal guardian (if a minor) to contact the site 
staff or investigator immediately if she experiences any of the following from Day 1 to 
Day 7 after vaccination to determine if an unscheduled reactogenicity visit is required as 
detailed in Section 8.10.5 OR inform the maternal participant or her parent(s)/legal 
guardian (if a minor) that if she experiences any of the following from Day 1 to Day 7 
after vaccination or is taking antipyretic medication at Day 7, then the study staff/field 
worker will continue to visit until resolution.  Furthermore, the maternal participant will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns as detailed in Section 8.10.5.
o
Fever ≥39.0°C (≥102.1°F).
o
Redness or swelling at the injection site measuring >20 measuring device units 
(greater than 10 cm).
o
Severe pain at the injection site.
o
Any severe systemic event.

Inform the maternal participants or her parent(s)/legal guardian (if a minor) that if a 
temperature of ≥38.0°C (≥100.4°F) is recorded during the collection of diary data, she 
will be required to have a rapid test for malaria as per local practice and details will be 
recorded in the diary (if applicable, based on local practice).

Remind maternal participants or her parent(s)/legal guardian (if a minor) that study staff 
may contact them to obtain additional information on events entered into the e-diary.
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
Remind maternal participants or their parent(s)/legal guardian (if a minor) to inform the 
study staff of any AEs and SAEs that occur for the duration of the trial as described in 
Section 8.2 and Section 10.2.

Remind the maternal participant or her parent(s)/legal guardian (if a minor) to bring the 
completed e-diary to the next visit (if applicable).

Complete the source documents.

The investigator or an authorized designee completes the CRFs, and the blinded 
dispenser/administrator completes the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.

Maternal participants or their parent(s)/legal guardian (if a minor) will be instructed to 
contact the site to report any significant illness (new or worsening), any medically 
attended respiratory events (eg, doctor’s visit, emergency room visit), or any 
hospitalization that occurs during the study period as detailed in Section 8.10.6.

Request the maternal participant and her parent(s)/legal guardian (if a minor) to contact 
the site if she goes into labor/is admitted to the maternal unit (The study staff/field worker 
will contact the maternal participant prior to the next study visit to remind her, if 
applicable).
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After Vaccination)
If delivery occurs before this visit, this visit will not be conducted.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

Review the participant’s e-diary data. Collect stop dates of any e-diary events ongoing 
on the last day that the e-diary was completed and record stop dates in the CRF.

Record details of any MA-RTI, including the diagnosis.

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.
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
Record AEs and SAEs as described in Section 8.2 and Section 10.2. Note: Active 
elicitation and collection of AEs and SAEs through 28 days after vaccination must occur 
even if delivery occurs within 28 days after vaccination.

The investigator or an authorized designee completes the CRF.

Maternal participants and their parent(s)/legal guardian (if a minor) will be instructed to 
contact the site to report any significant illness (new or worsening), any medically 
attended respiratory events (eg, doctor’s visit, emergency room visit), or any 
hospitalization that occurs during the study period as detailed in Section 8.10.6.

Request the maternal participant and her parent(s)/legal guardian (if a minor) to contact 
the site if she goes into labor/is admitted to the maternal unit (The study staff/field worker 
will contact the maternal participant prior to the next study visit to remind her, if 
applicable).
8.10.3. Delivery (Maternity Unit)
The delivery visit spans the time from when a participant is admitted in labor through 
discharge following delivery of her infant. Protocol-specified procedures associated with 
this delivery visit may be done at any time during this period.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

If available, record the maternal participant’s group B streptococcal (GBS) status and if 
any medication was given for intrapartum antibiotic prophylaxis (IAP). Note: Positive 
GBS carriage should not be reported as an adverse event in the CRF if performed in the 
setting of routine prenatal care.

Record details of any nonstudy vaccinations given since the last visit.

Collect a blood sample of approximately 15 mL for serologic assessments.  Note: The 
maternal participant’s blood sample can be taken at any time during the delivery visit, 
preferably before delivery. In the event that the blood sample cannot be obtained 
before delivery, the sample should be collected as close to delivery as possible and at 
most 48 hours postpartum.
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments 
must also be collected.  Cord blood is collected from the umbilical cord vein attached to 
the placenta prior to the blood clotting within the cord and after the umbilical cord has 
been clamped and cut.  This sample should be labeled with the infant’s participant ID 
number.
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
Record pregnancy outcome information, including vital status of the infant (live, 
stillbirth, etc.), mode of delivery (vaginal delivery or cesarean section), and the use of any 
assisted devices (forceps or vacuum).

Record details of any MA-RTI, including the diagnosis.

Record AEs as described in Section 8.2 and Section 10.2.

Ask the maternal participants and her parent(s)/legal guardian (if a minor) to contact the 
site to report any significant illness (new or worsening), any medically attended 
respiratory events (eg, doctor’s visit, emergency room visit), or any hospitalization that 
occurs during the study period as detailed in Section 8.10.6.

Ask the maternal participant and her parent(s)/legal guardian (if a minor) to contact the 
site staff or investigator if her newborn infant meets the MA-RTI study criteria OR the 
study staff/field worker will contact the maternal participant/legal guardian(s) weekly to 
remind them to report any MA-RTI (if applicable).

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 210 Days After 
Delivery)

Obtain details of any postnatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [eg, HBIG]) or Rho(D) immune globulin [eg, RhoGAM]) or blood 
products (eg, whole blood, packed cells) given since the last visit.

Record details of any nonstudy vaccinations given since the last visit.

Record details of any MA-RTI, including the diagnosis.

Ask the maternal participant and her parent(s)/legal guardian (if a minor) to contact the 
site staff or investigator if her infant meets the MA-RTI study criteria OR the study 
staff/field worker will contact the maternal participant/legal guardian(s) weekly to remind 
them to report any MA-RTI, if applicable.

Record AEs as described in Section 8.2 and Section 10.2.

Complete the maternal participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.10.5. Unscheduled Reactogenicity Visits
If the maternal participant or her parent(s)/legal guardian (if a minor) reports 1 or more of the 
following, a contact must occur as soon as possible between the maternal participant and the 
investigator, or a medically qualified member of the study site staff, to assess if an 
unscheduled reactogenicity visit is required OR based on local practice in certain 
countries/locales, maternal participants will be referred to the appropriate healthcare facility 
at the discretion of the study staff/field worker if there are any concerns regarding 
reactogenicity events, including:

redness at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

swelling at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

severe injection site pain on the arm that the investigational product was 
administered, 

fever ≥39.0°C (≥102.1°F).
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The maternal participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or

The participant/study staff/field worker recorded an incorrect value in the e-diary 
(confirmation of an e-diary data entry error), or

The investigator or appropriate designee determines that the visit is not required.
This contact will be recorded in the maternal participant’s source notes and in the CRF.
Any ongoing reactions must be assessed at the next scheduled visit.
The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure oral temperature.

Measure the participant’s heart rate.

Measure the participant’s blood pressure (seated).
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
Measure the minimum and maximum diameters of redness (if present) on the arm in 
which the investigational product was administered.

Measure the minimum and maximum diameters of swelling (if present) on the arm in 
which the investigational product was administered.

Assess if necrosis is present at the injection site on the arm in which the investigational 
product was administered.

Assess if any exfoliative dermatitis is present.

Assess any injection site pain on the arm in which the investigational product was 
administered that is present in accordance with the reactogenicity grading scale provided 
in Section 8.2.1.1.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 8.2.1.2.

Ask the participant or her parent(s)/legal guardian (if a minor) if she attended an 
emergency room visit or was hospitalized.

For severe pain at the injection site resulting in an emergency room visit or 
hospitalization, severe systemic events associated with an emergency room visit or 
hospitalization, any necrosis on the arm in which the investigational product was 
administered, or exfoliative dermatitis, the investigator or qualified designee must assess 
these events in accordance with the intensity AE grading scale provided in
Section 8.2.1.1 and Section 8.2.1.2.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

Complete the participant’s source documents.

The investigator or an authorized designee will complete the CRFs.

The study staff/field worker may contact the participant to obtain additional information 
on events entered into the e-diary, as appropriate.
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8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria – Maternal 
Participants

Starting from Day 1 after vaccination (where Day 1 is the day of vaccination) until the 
end of the study, all maternal participants will be monitored for MA-RTIs as detailed in 
Section 1.2.3.1 and Section 8.1.2. Maternal participants or their parent(s)/legal guardian 
(if a minor) should notify the site and/field worker of the occurrence of any MA-RTIs 
immediately but no later than the next study visit. Note: Site contact may be by an 
electronic method of communication (including but not limited to electronic messaging, 
short message service [SMS], text, email), by phone call, or by face-to-face contact.

The definition of maternal RTI includes 1 or more of the following signs and/or 
symptoms:
o
New or increased sore throat
o
New or increased cough
o
New or increased nasal congestion
o
New or increased nasal discharge
o
New or increased wheezing
o
New or increased sputum production
o
New or increased shortness of breath

Record the details of any MA-RTI, including the diagnosis, the medically attended visit 
location (hospital, outpatient visit, emergency room, urgent care, or home visit), duration 
of hospitalization, intensive care unit (ICU) duration if applicable, prescribed medications 
for the MA-RTI, assessments including RSV test result (eg, NAAT, rapid antigen 
detection tests, or any other molecular diagnostic test), if available, and the final 
diagnosis.

Record the details of any nonstudy vaccinations.

Record AEs as described in Section 8.2 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.11. Procedures – Infant Participants
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After Birth)

Manually assign a single infant participant identifier. This will be assigned manually by 
the site using the following convention: the infant participant’s identifier will be the 
maternal participant’s IRT-generated numeric ID but with the fifth digit changed to a 2 
(eg, if the maternal participant is given number 10011001, then the infant will be 
10012001).

Collect a cord blood sample of approximately 10 mL for immunogenicity assessments.  
Cord blood is collected from the umbilical cord vein attached to the placenta prior to the 
blood clotting within the cord and after the umbilical cord has been clamped and cut.  
This sample should be labeled with the infant’s participant ID number.

If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 24 hours, but up to 7 days after birth.  The volume of blood collected 
will be based on the weight of the infant (refer to Table 3).

Ensure and document that all the infant inclusion criteria and none of the infant exclusion 
criteria are met.

Collect demography (including complete date of birth [ie, dd-Mmm-YYYY], sex, race, 
and ethnicity).  The date of birth will be collected to critically evaluate the immune 
response.
o
Obtain and record the infant’s length, head circumference, and weight at birth.
o
Obtain and record the infant’s birth data, including GA and appearance, pulse, 
grimace, activity, and respiration (Apgar) score.
o
Obtain and record background factors as described in Section 10.5.
o
Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.
o
Standard-of-care vital signs and examination procedures can be considered for use in 
the study provided they were performed within 72 hours after birth. Note: Please 
reference the physical examination procedures below for details.
o
Perform a physical examination, if not performed as part of standard of care, noting 
any clinically significant abnormalities within the following body systems: general 
appearance; skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; back; 
musculoskeletal; extremities; genitourinary; neurological; and lymph nodes.  
Abnormal results must be recorded on source documents as well as the physical 
examination pages of the CRF; only if the abnormal finding is deemed to be clinically 
significant should this be recorded on the AE pages of the CRF.
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o
Record details of any congenital anomalies on the AE page of the CRF, and report as 
an SAE as described in Section 10.2.3.

Record any medication as described in Section 6.5.6.

Obtain details of any Ig (including monoclonal antibodies [eg, Synagis] or immune 
globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given to the 
infant participant since birth.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Review the weekly contact schedule with the parent(s)/legal guardian(s) and collect 
contact information OR remind the parent(s)/legal guardian(s) that a field worker will 
contact them weekly to remind them to report any MA-RTI (if applicable).

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria. An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of this study visit.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate. Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the
study visit.
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
Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the site source documents. Newly 
identified abnormal findings must be recorded on source documents and, if considered 
clinically significant in the judgment of the investigator/examiner, on the AE page of the 
CRF. Note: Standard-of-care examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit.
o
Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee 
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria.  An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every 7 days 
from birth until the 6-month follow-up visit to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The weekly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.7.1 for guidance on reported cases of 
MA-RTIs in infant participants during the first 6 months after birth.
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8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.

Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.
Note: Standard-of-care examination procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.
o
Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants.

Ask the parent(s)/legal guardian(s) to contact the investigator immediately if any 
significant illness or hospitalization occurs or if the infant meets the MA-RTI visit
criteria.  An RTI study visit, along with a nasal swab collection, must be performed 
for all hospitalizations due to an RTI and severe MA-LRTIs as described in 
Section 1.2.4.1 and Section 8.11.8.
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
If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care as 
described above, noting any clinically significant abnormalities in the source documents. 
Newly identified abnormal findings must be recorded on source documents and, if 
considered clinically significant in the judgment of the investigator/examiner, on the AE 
page of the CRF. Only applicable if a clinic visit is conducted. Note: Standard-of-care 
examination procedures can be considered for use at this study visit, if they were 
performed within the window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants except for infant participants born during the first year of the study.

The investigator or an authorized designee completes the CRF for infant participants born 
during the first year of the study. Note: An additional 12-month blinded follow-up period 
for longer-term RTI surveillance and safety oversight will be included for these 
participants.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Confirm the understanding of the infant participant’s parent(s)/legal guardian(s) 
regarding site contact for the study, which is approximately every month (28 to 35 days) 
until the end-of-study visit. Ask the parent(s)/legal guardian(s) to contact the 
investigational site/field worker promptly if the infant meets the MA-RTI visit criteria.  
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The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants.

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days After Birth; 
Infant Participants Born During the First Year of the Study Only)

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants.
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Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 742 Days After 
Birth; Infant Participants Born During the First Year of the Study)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if 
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care, noting 
any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF. 
Only applicable if a clinic visit is conducted. Note: Standard-of-care examination 
procedures can be considered for use at this study visit, if they were performed within the 
window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants born during the first year of the study.
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8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 Months After 
Delivery)

This is an active surveillance period spanning from birth through 6 months after delivery 
(Visit 3). Note: Reporting MA-RTI events should commence 72 hours after the infant’s 
delivery.  Respiratory distress events associated with and within 72 hours of birth should 
not be captured as MA-RTI events for the study but should be captured as AEs/SAEs 
(if applicable).

The sponsor may alter the frequency of the weekly contacts or the duration of 
surveillance for MA-RTI based on RSV surveillance data or other operational factors.
8.11.7.1. Study Visits Following a Medically Attended RTI – Hospital, Home, or Clinic 
Visit

Contact the infant participant’s parent(s)/legal guardian(s) approximately every week 
(7 to 10 days) from birth until Visit 3 (6-month follow-up visit), to remind the 
parent(s)/legal guardian(s) to contact the investigational site promptly if the infant meets 
the criteria for an MA-RTI event.  The weekly contact may be via the e-diary device or 
study-related mobile application, text, email, phone call, or face-to-face contact with the 
site staff/field worker. Please refer to Table 1 regarding clinical signs and symptoms that 
meet the study definition of an MA-RTI, and Section 1.2.4.1 for study-required 
assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by:
o
The infant caregiver during or within 10 days following the MA-RTI visit
OR
o
The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an event requiring a visit to a healthcare provider, the site staff 
and/field worker should confirm, based on information provided, whether the event meets 
the criteria for an MA-RTI. Please refer to Table 1 and Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

When an infant MA-RTI criterion is met or confirmed, the site/field worker will obtain 
records from the medically attended visit and record the healthcare information as 
detailed in Appendix 6.
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When an infant MA-RTI criterion is met or confirmed, the infant participant will be 
seen as soon as possible and optimally within 72 hours or up to 10 days for an RTI study 
visit by the investigational site staff or qualified designee.

The infant participant may be seen either at the time of the MA-RTI, at home or at the 
study site (if discharged), or if the infant participant has been hospitalized or is receiving 
treatment at another medical facility, the site staff/field worker can conduct the RTI study 
visit at those facilities.
o
If the RTI study visit is not performed within 72 hours of the event, it should still be 
performed, including the collection of nasal swab specimens.
o
Targeted assessments at an RTI study visit include but are not limited to:
o
Respiratory signs: lower chest wall indrawing.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Nasal swab collection from the infant participant for testing at the central 
laboratory.
o
Body weight

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site/field worker if the infant’s 
illness worsens, or if the infant is hospitalized.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Compile the adjudication submission package for the event as detailed in Section 8.1.
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8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit Criteria

This is a long-term surveillance procedure for all infant participants from 6 months after 
delivery (Visit 3) until the last study visit.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) from Visit 3 (6-month follow-up visit) until the end-of-study visit, to 
remind the parent(s)/legal guardian(s) to contact the investigational site promptly if the 
infant meets the criteria for an MA-RTI visit.  The monthly contact may be via the 
e-diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by:

The infant caregiver during or within 10 days following the MA-RTI visit
OR

The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an MA-RTI, the site should obtain additional information and 
determine whether the event also meets the study definition of a severe MA-LRTI.

Note: Severe MA-LRTI is defined in Table 1.

The site/field worker will obtain records from the medically attended visit and record the 
healthcare information as detailed in Appendix 6.

When an infant MA-RTI criterion is confirmed and also meets the study definition of 
hospitalization due to an RTI or a severe MA-LRTI, the infant participant will be seen 
as soon as possible and optimally within 72 hours or up to 10 days for an RTI study 
visit that includes a nasal swab collection by the investigational site staff/field worker. 
The staff/field worker will obtain the nasal swab optimally within 72 hours or up to 
10 days of the event with the infant participant either at home (if discharged) or, if the 
infant participant has been hospitalized or receiving treatment at another medical facility, 
the site staff/field worker will conduct the visit at those facilities.

Note: Nasal swab collection from the infant participant is for testing at the central 
laboratory.
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A targeted RTI study visit will be required for all reported cases of hospitalization due to 
an RTI or severe MA-LRTI only, and this includes but is not limited to:
o
Respiratory signs: lower chest wall indrawing, failure to respond/unconsciousness.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Body weight

A targeted RTI study visit is not required for an MA-RTI event not meeting the definition 
of hospitalization due to an RTI or severe MA-LRTI.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the MA-RTI event, including emergency room or
hospitalization details with admission and discharge date (if applicable).

Record any medication as described in Section 6.5.6.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.  Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site if the infant’s illness worsens, 
or if the infant is hospitalized.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Compile the adjudication submission package for hospitalizations due to an RTI and 
severe MA-LRTI events only as detailed in Section 8.1.
8.12. Nasal Swab Collection
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI 
visit during the RSV surveillance period from 72 hours after delivery until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of an MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1).
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The nasal swab sample is to be collected as soon as possible and optimally within 72 hours or 
up to 10 days of an MA-RTI visit in either the infant participant’s home or a medical setting 
(eg, clinic, hospital, etc.) by the investigational site staff.
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), the 
nasal swab can be collected by the infant’s caregiver or the HCP assessing the infant 
(in addition to any samples obtained in the course of routine clinical care) for processing at a 
Pfizer central laboratory, as detailed in Section 8.11.7.1 and Section 8.11.8.
In the event that these restrictions prevent taking RTI study swabs at the investigational site, 
the infant’s caregiver will be given a study nasal swab collection kit including shipping 
instructions, to be used if necessary. The infant caregiver or the HCP assessing the infant 
during an MA-RTI visit may assist the investigational sites by collecting of the study nasal 
swab samples, as required.
Note: Investigational site staff will review the procedures for nasal swab sample collection 
and shipping instructions with each infant caregiver and ensure that he/she understands the 
appropriate procedures for collecting and packaging samples for shipment to the study site.
The process for nasal swab collection and transport to the Pfizer central laboratory via study 
sites is detailed in the ISF.
8.13. Communication and Use of Technology
In a study of this duration that is event-driven, it is vital to ensure that communication 
between the study site and the maternal participant and parent(s)/legal guardian(s) is 
maintained to ensure that endpoint events are not missed.  This study will employ various 
methods, tailored to the individual participant (maternal and/or infant participant), to ensure 
that communication is maintained, and study information can be transmitted securely.  Using 
appropriate technology, a communication pathway between the maternal participant and 
parent(s)/legal guardian(s) and the study site staff will be established.  The maternal 
participant and the parent(s)/legal guardian(s) may be able to utilize their own devices to 
access this technology, or use a device provided by the sponsor.  Traditional methods of 
telephone communication will also be available. The technology solution may facilitate the 
following:

Contact with the investigator.

The ability of the maternal participant/parent(s)/legal guardian(s) to report MA-RTI visits
associated with the infant participant.

An alert in the event that the maternal or infant participant is hospitalized.

Visit reminders.
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
Messages of thanks and encouragement from the study team.

A platform for recording local reactions and systemic events (e-diary).
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in an SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Estimands and Statistical Hypotheses
The null hypothesis to be tested concerns VE for the primary endpoints. The RSV vaccine 
will be compared to placebo, testing the hypotheses H0: VE ≤20% vs Ha: VE 20%. For all 
secondary efficacy endpoints, the RSV vaccine will be compared to placebo, testing the 
hypotheses H0: VE ≤0% vs Ha: VE >0%. Hypothesis testing of the secondary endpoints is 
conditional upon rejection of the null hypothesis for at least 1 of the primary endpoints.
9.1.1. Estimands – Infant Participants
9.1.1.1. Efficacy
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with key protocol criteria (evaluable participants):

VE, defined as the percentage relative risk reduction in the incidence of MA-LRTI due to 
RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of severe MA-LRTI 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of hospitalization 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of all-cause 
MA-LRTI in the RSV vaccine group, relative to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  For participants who 
discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
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9.1.1.2. Immunogenicity
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with the key protocol criteria (evaluable participants):

Functional antibody levels estimated by the GMT for RSV A and RSV B serum
neutralizing titers.

Geometric mean ratio (GMR), estimated by the ratio of the GMTs for RSV A and RSV B
serum neutralizing titers of the RSV vaccine group to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as missing completely at random (MCAR) is assumed.  For participants 
who discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.3. Safety
In infant participants born to the maternal participants receiving 1 dose of investigational 
product:

The percentage of infant participants with specific birth outcomes.

The percentage of infant participants having AEs from birth through 1 month of age.

The percentage of infant participants having SAEs, NDCMCs, and new diagnosed 
congenital anomalies from birth through the last study visit.
Missing AE dates and missing AE intensity will be handled according to Pfizer safety rules.
9.1.2. Estimands – Maternal Participants
9.1.2.1. Immunogenicity
In maternal participants receiving 1 dose of investigational product and in compliance with 
the key protocol criteria (evaluable participants):

The immune response, estimated by the GMT for RSV A and RSV B serum neutralizing 
titers.

The immune response, estimated by the GMFR from baseline in RSV A and RSV B 
serum neutralizing titers.

GMR, estimated by the ratio of the GMTs for RSV A and RSV B serum neutralizing 
titers of the RSV vaccine group to the placebo group.
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
Geometric mean of the IgG levels against RSV prefusion F.

Geometric mean of the Ig levels to nonvaccine RSV antigens.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as MCAR is assumed.  For participants who discontinue from the study 
or have major protocol violations, all postdiscontinuation or postviolation observations will 
be censored.
9.1.2.2. Safety
In maternal participants receiving 1 dose of investigational product:

The percentage of maternal participants reporting AEs through 1 month after vaccination.

The percentage of maternal participants reporting obstetric complications and SAEs 
through the end of the study.

The percentage of maternal participants reporting local reactions within 7 days of 
vaccination.

The percentage of maternal participants reporting systemic events within 7 days of 
vaccination.
Missing e-diary data will not be imputed; missing AE dates and missing AE intensity will be 
handled according to Pfizer safety rules.
9.2. Sample Size Determination
This is an event-driven study. Sample size is determined as the number of participants to be 
randomized that is expected to accrue the required number of primary-endpoint cases in the 
evaluable population. In this study there are 2 primary endpoints, and success on either 
primary endpoint is sufficient (see Section 9.1); power for the study overall is therefore at 
least as high as the power for either primary endpoint individually. In the evaluable 
population, a total of at least 67 cases of MA-LRTI due to RSV within 90 days of birth will 
ensure more than 90% power to reject the null hypothesis when true VE is 70% at 90 days. 
This also accounts for potential use of an alpha of 1.25% 1-sided within the multiplicity 
adjustment. There is no explicit case target for the endpoint of severe MA-LRTI due to 
RSV; depending on the assumed true VE, power for that individual hypothesis may be lower, 
but the power for the primary endpoint family will be at least 90%. Hypotheses about VE 
may be restated as hypotheses about the proportion of cases in the RSV vaccine group, 
conditional upon a fixed total number of cases. If this proportion is p, the null hypothesis H0: 
VE ≤20% is equivalent to H0: p ≥0.444; the assumption of VE = 70% corresponds to p =
0.231. Power was evaluated by the exact binomial test, and the case target established as that 
number k for which power is guaranteed to be at least 90%, for all k* ≥k. The calculation 
accounted for the study design (1:1 randomization of participants to RSV vaccine : placebo), 
planned interim analyses of efficacy (see Section 9.5), and an overall type 1 error of 2.5% 
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1-sided across the 2 primary endpoints. This global study is planned to be conducted in the 
United States and other high-income countries as well as LMICs. Incidence rates of the 
primary endpoints are expected to vary in different regions. Based on the cases of MA-LRTI 
due to RSV through 90 days, available at the first interim analysis of the study conducted in 
April 2022, the pooled rate of evaluable cases in the study (placebo and RSV vaccine groups 
combined) is approximately 0.95%. With this rate, the current enrollment should ensure that 
the case target of at least 67 cases is achieved. However, if fewer than 67 cases have 
occurred at the end of the 2022 southern hemisphere RSV season, the final analysis will be 
performed at that point. It is acknowledged that there may be some loss of power in that 
event.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined for infant and maternal 
participants:
Population
Description
Enrolled
All maternal participants who sign the ICD.
Randomly assigned to 
investigational product
All maternal participants who are assigned a randomization 
number in the IRT system.
Evaluable efficacy –
infant (per-protocol)
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized at least 14 days prior to delivery, did not 
receive palivizumab or another monoclonal antibody targeting 
RSV, have no major protocol violations, and did not have 
transfusions of more than 20 mL/kg of any blood products at 
<180 days.
Modified intent-to-treat 
(mITT) efficacy – infant
All infant participants who are born to vaccinated maternal 
participants.
Evaluable 
immunogenicity – infant
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized, have blood drawn for assay testing 
within the specified time frame, have valid and determinate 
assay results for the proposed analysis, and have no major 
protocol violations.
Evaluable 
immunogenicity –
maternal
All maternal participants who are eligible, receive the 
investigational product to which they were randomized, have 
blood drawn for assay testing within the specified time frame, 
have valid and determinate assay results for the proposed 
analysis, and have no major protocol violations.
mITT immunogenicity –
infant
All infant participants who are born to vaccinated maternal 
participants and have at least 1 valid and determinate assay 
result for the proposed analysis.
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Population
Description
mITT immunogenicity –
maternal
All randomized maternal participants who receive 
investigational product and have at least 1 valid and determinate 
assay result for the proposed analysis.
Safety – infant
All infant participants who are born to vaccinated maternal 
participants.
Safety – maternal
All randomized maternal participants who receive 
investigational product.
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock for the first planned analysis 
and will describe the participant populations to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data.  This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The analysis of efficacy will use a conditional exact test based on the 
binomial distribution of the number of disease cases in the RSV vaccine 
group, given the total number of cases in both groups. The incidence of 
MA-LRTI due to RSV and severe MA-LRTI due to RSV in infant 
participants will be evaluated in both groups up to 90 days, 120 days, 
150 days, and 180 days after birth.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.

The 2 primary endpoints of MA-LRTI due to RSV and severe 
MA-LRTI due to RSV will be tested in parallel using a multiplicity 
adjustment procedure. Success of the trial requires rejection of the null 
hypothesis (ie, a CI lower bound >20%) for either one of the 2 primary 
endpoints.

Testing of the 2 primary endpoints across the time intervals will follow a 
fixed sequence with a gatekeeping strategy. First, the hypothesis 
pertaining to the incidence of the 2 primary endpoints within 90 days 
after birth will be tested, at the full multiplicity-adjusted alpha level, 
using a multiplicity adjustment for the 2 endpoints. If that null 
hypothesis cannot be rejected, testing ends. Otherwise, testing proceeds 
to the incidence within 120 days after birth. Only primary endpoint(s)
that are successful at all earlier time intervals will be considered at 
subsequent intervals. Testing will proceed to the endpoints evaluated at 
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Endpoint
Statistical Analysis Methods
150 days and 180 days, conditional on rejection of the null hypotheses for 
all earlier time intervals. Refer to the SAP for full details of the testing 
sequence and multiplicity correction strategy.

There may be up to 2 interim analyses of the MA-LRTI-due-to-RSV
endpoint when there is an adequate number of cases (at least 43 cases
within 90 days). Based on the fraction of cases included in an interim 
analysis, an alpha level will be derived based on a Lan-DeMets
implementation of the O’Brien-Fleming alpha spending function. See 
Section 9.5 for more details.

At the interim analyses there will also be an assessment for futility, based 
on conditional power for the MA-LRTI-due-to-RSV endpoint. If the 
probability of success at the end of the trial is low, given the interim 
analysis results and the initially assumed VE is applied to the remaining 
data, consideration will be given to stopping the study for futility.

The first interim analysis occurred in April 2022 and did not result in 
stopping of the study for efficacy or futility. The nominal 1-sided alpha 
used at that interim analysis was 0.00085, so the remaining 1-sided alpha 
is at least 0.02415. Therefore, a conservative 1-sided alpha of 0.02415 is 
planned as the adjusted alpha level for the final analysis, to be shared 
between the 2 primary endpoints as defined in the SAP.

CIs for VE will be calculated using the appropriate multiplicity-adjusted 
alpha level α. If the lower 100(1 - α)% confidence limit for VE exceeds 
20%, the null hypothesis for that endpoint will be rejected.

At the end of the trial, the RSV vaccine may be deemed efficacious if 
there are 20 or fewer cases of MA-LRTI due to RSV in the RSV vaccine 
group out of the 67 total primary-endpoint cases at 90 days.  This 
corresponds to estimated VE = 57% with 97.6% CI = (21%, 78%). For 
severe MA-LRTI, assuming a total of 34 cases occur, the vaccine may be 
deemed efficacious if there are 8 or fewer cases in the RSV vaccine 
group.  This corresponds to estimated VE = 69% with 97.6% CI = (22%, 
90%).

Kaplan-Meier curves showing accrual of primary-endpoint cases over 
180 days will be presented.

There will be a sensitivity analysis of the primary endpoints to examine 
the impact of missing RSV swab results. Details are provided in the 
SAP.
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Endpoint
Statistical Analysis Methods
Secondary

The analysis of secondary efficacy endpoints will use the exact 
conditional binomial method, as for the primary endpoint. Secondary 
endpoints will be examined at the final analysis only. VE will be 
estimated along with 2-sided 95% CI.

Inference for the secondary endpoints will be conditional upon 
demonstrating success for one of the primary efficacy endpoints. The 
secondary endpoints of hospitalizations due to RSV, all-cause MA-LRTI, 
and MA-LRTI beyond 180 days will be tested in parallel so as to 
preserve the overall type 1 error across primary and secondary endpoint 
families at no more than 2.5% 1-sided. Multiplicity correction strategies 
will be defined in the SAP. VE will be evaluated sequentially at 90 days, 
120 days, 150 days, 180 days, and 360 days for hospitalization due to 
RSV and all-cause MA-LRTI and at 210 days, 240 days, 270 days, and 
360 days for MA-LRTI due to RSV. Testing will only proceed to later 
time points conditional on success of all previous time points.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.
Exploratory

The incidence in infant participants of MA-RTIs due to RSV with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized.

The incidence in infant participants of MA-RTIs due to any cause with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized. All MA-RTIs and severe MA-LRTIs will be summarized 
separately.

The incidence in infant participants of MA-LRTIs due to RSV occurring 
361 to 730 days after birth will be summarized.

The incidence in infant participants of severe MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized.

The incidence in infant participants of hospitalization due to RSV 
occurring 181 to 730 days after birth will be summarized.

The primary endpoint through 180 days after birth will be summarized 
separately as cases associated with RSV subgroup A or RSV subgroup B 
infection.
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Endpoint
Statistical Analysis Methods

The primary endpoint through 180 days after birth will be summarized 
by interval from vaccination to delivery and by GA at the time of 
vaccination.

The incidence of MA-RTI, MA-LRTI, and severe MA-LRTI due to RSV 
occurring 0 to 730 days after birth in premature infants (<37 weeks GA) 
will be summarized.

The incidence of MA-RTI due to any cause in maternal participants from 
vaccination through 180 days after delivery will be summarized.
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

A 3-tier approach will be used to summarize AEs. For both Tier 1 and 
Tier 2 events, the 95% CIs for the difference in the percentage of 
participants reporting the events between the RSV vaccine group and the 
placebo group will be calculated using the test statistic proposed by 
Miettinen and Nurminen; in addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in the percentage of 
participants reporting the events, based on the same test statistic and under 
the assumption that the test statistic is asymptotically normally distributed.  
A Medical Dictionary for Regulatory Activities (MedDRA) preferred term 
is defined as a Tier 2 event if there are 1% or more participants in at least 
1 vaccine group reporting the event.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Secondary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.
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Endpoint
Statistical Analysis Methods

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Exploratory 
Subgroup analyses of safety will be performed based on age at vaccination 
(18 years, ≥18 years). These and other exploratory analyses will be 
described in the SAP, finalized before first database lock.
9.4.3. Other Analyses
9.4.3.1. Immunogenicity Analyses
Immunogenicity endpoints are exploratory in the study.  The analyses of immunogenicity 
endpoints will be based on the evaluable populations.  An additional analysis will be 
performed based on the mITT populations if there is enough difference between the mITT 
populations and the evaluable populations.  Immunogenicity data for maternal participants 
and infant participants will be summarized separately, with the exception of 
maternal-to-infant placental transfer analysis.  Participants will be summarized according to 
the vaccine group to which they (for maternal participants) or their mothers (for infant 
participants) were randomized.
The secondary and exploratory immunogenicity endpoints will be described by the following 
summaries and the 95% CIs:

GMT of the RSV A and RSV B serum neutralizing titers at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMT of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMFR for RSV A and RSV B serum neutralizing titers from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMFR of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMR of the RSV vaccine group to the placebo group for the RSV A and 
RSV B serum neutralizing titers at each available time point after vaccination (maternal 
participants and infant participants, separately).
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
GMR of the RSV vaccine group to the placebo group for the combined RSV A/B serum
neutralizing titers at each available time point after vaccination (maternal participants and 
infant participants, separately).

Geometric mean of the IgG levels against RSV prefusion F and Ig levels to nonvaccine 
RSV antigens at each available time point by vaccine group (maternal participants and 
infant participants, separately).

Geometric mean of IgG subclass levels (minimally IgG1) against RSV prefusion F at 
each available time point by vaccine group (maternal participants only).
Empirical reverse cumulative distribution curves (RCDCs) for combinations of time points 
and vaccine groups will be presented for RSV A and RSV B serum neutralizing titers.
A sensitivity analysis will be performed to exclude immunogenicity data from mothers and 
their infants following onset of RSV infection between vaccination and delivery (based on 
evidence from the nonvaccine antigen assay).
Subgroup analyses of the secondary and exploratory immunogenicity endpoints will be 
performed, including an analysis based on GA at the time of vaccination, age at vaccination 
(18 years, ≥18 years), time from vaccination to delivery, and by country subcategories. All 
subgroup analyses will be defined in the SAP.
In addition, the maternal-to-infant placental transfer ratio (infant/mother) of RSV A and 
RSV B serum neutralizing titers and associated 95% CI will be summarized.
9.4.3.2. Healthcare Utilization Analyses
Healthcare utilization endpoints are exploratory in the study; these analyses will be described 
in the SAP and finalized before first database lock. For these analyses, details of healthcare 
resource utilization for all infants will be assessed at each MA-RTI visit from 72 hours after 
the infant’s delivery through the last study visit (730 days after birth). Univariate summaries
of healthcare resource utilization variables will be compared between the RSVpreF and 
placebo groups. The summarized variables may include the following: number and type 
(eg, respiratory, reactive airway disease [RAD]/asthma/wheezing) of medical visits 
(eg, outpatient, urgent care, emergency room, hospitalization, ICU), length of hospital stay, 
requirement for mechanical ventilation (yes/no, total number of episodes, total number of 
hours/days on treatment), requirement for IV fluids, requirement for respiratory diagnostic 
procedures (eg, chest radiograph, supplemental oxygen, pulse oximetry), requirement for 
prescriptions (eg, total number of prescriptions, selected respiratory medications 
[eg, bronchodilators, corticosteroid therapy, racemic epinephrine]), and antibiotic use 
(eg, total number of prescriptions, number of use days).
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9.5. Interim Analyses
Interim analyses may be performed to assess efficacy and safety after at least 43 cases of 
MA-LRTI due to RSV within 90 days have occurred. Because of the relatively low number 
of cases of severe MA-LRTI due to RSV expected, the interim analyses may not consider 
that endpoint. Interim analysis results may be used for internal business decisions regarding 
future study planning, stopping for futility, or stopping for early success.
The order of cases included in the interim analysis will be determined by the adjudication 
committee as those first confirmed as meeting the protocol-defined criteria. When the target 
number of cases for an interim analysis is reached, it is possible that additional potential 
cases will be under adjudication. Only cases that have been fully adjudicated prior to taking a 
data snapshot will be included in an interim analysis.
The analysis of efficacy will utilize an O’Brien-Fleming alpha spending rule based on the 
fraction of cases of MA-LRTI due to RSV within 90 days available. The exact number of 
cases at each interim analysis is not fixed and may be decided based on operational reasons. 
However, no fewer than 43 cases will be included in the first interim analysis.  The alpha 
levels used at interim and final analyses will depend on the exact fraction of cases available 
at the interim analysis.
The first interim analysis occurred in April 2022 and did not result in stopping of the study 
for efficacy or futility. The nominal 1-sided alpha used at that interim analysis, in 
accordance with the alpha spending function, was 0.00085, so the remaining 1-sided alpha 
for the study is at least 0.02415. A conservative 1-sided alpha of 0.02415 is planned as the 
adjusted alpha level for the final analysis, to be shared between the 2 primary endpoints as 
defined in the SAP.
Testing of the primary endpoints at the interim analysis will follow the sequence of 
interval-specific tests as described in Section 9.4.1.  However, consideration will be given to 
stopping the study for efficacy only if all time intervals through 180 days indicate statistically 
significant efficacy. Secondary endpoints will not be tested at the interim analysis.
Futility will also be assessed using conditional power. Full details will be defined in the 
SAP. For example, if there are 62 cases available for the interim analysis, Table 7 indicates 
case splits for which stopping the study will be considered. The actual number of cases 
available may be slightly higher or lower than 62, and the decision rules amended 
accordingly. These examples utilized the original study final case target of 124 cases.
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Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals at an 
Interim Analysis
Total Cases
RSV Vaccine 
Group Cases
Placebo Group 
Cases
VE (CI)a
Notes
43 (First interim)
24
19
-26% (-145%, 34%)
Conditional power 
<20%,b possible 
futility declaration
43 (First interim)
7
36
81% (23%, 97%)
Maximum number 
of vaccine group
cases permitted to 
declare VE >20%
62 (Second interim)
29
33
12% (-49%, 49%)
Conditional power 
<20%,b possible 
futility declaration
62 (Second interim)
15
47
68% (24%, 88%)
Maximum number 
of vaccine group
cases permitted to 
declare VE >20%
Abbreviation: VE = vaccine efficacy.
a.
Confidence level for efficacy declaration based on available alpha at each interim; 95% confidence level 
for futility.
b.
Other conditional power levels may be considered as a trigger for a futility decision.
Before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan, and method of maintaining the study blind as per Pfizer’s standard 
operating procedures (SOPs) will be documented and approved in the DMC charter.  In 
addition, the analysis details must be documented and approved in an interim analysis SAP 
or final SAP.
9.5.1. Data Monitoring Committee
This study will use an E-DMC.  Refer to the E-DMC charter for further details.
The E-DMC will review safety data at defined intervals as specified in the charter.  The 
E-DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.
The E-DMC may review unblinded data during closed meeting sessions; however, the 
sponsor will remain blinded and will not be permitted access to the randomization 
assignments until the database is locked and unblinded.
After each meeting, the E-DMC will make recommendations that may include continuing the 
study with or without modification or pausing or stopping vaccination for safety or other 
reasons.
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The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints, to regulatory authorities, as appropriate.
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
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10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the maternal 
participant and her parent(s)/legal guardian (if a minor) and answer all questions regarding 
the study.
Maternal participants must be informed that their participation is voluntary.  Maternal 
participants and their parent(s)/legal guardian (if a minor) will be required to sign a statement 
of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant and her parent(s)/legal guardian (if a 
minor) is fully informed about the nature and objectives of the study, the sharing of data 
related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data.
The participant and her parent(s)/legal guardian (if a minor) must be informed that his/her 
personal study-related data will be used by the sponsor in accordance with local data 
protection law.  The level of disclosure must also be explained to the participant.
The participant and her parent(s)/legal guardian (if a minor) must be informed that his/her
medical records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities.
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The investigator further must ensure that each study participant or his or her parent(s)/legal 
guardian(s) is fully informed about his or her right to access and correct his or her personal 
data and to withdraw consent for the processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants and parent(s)/legal guardian(s) must be reconsented to the most current version 
of the ICD(s) during their participation in the study.
A copy of the ICD(s) must be provided to the maternal participant or the parent(s)/legal 
guardian(s).
A study-specific assent form will be provided to maternal participants denoted to be “minor 
participants” as required by local regulations.  It is to be understood as the “minor” maternal 
participants will participate in a trial after having received age-appropriate information and is 
sometimes also referred to as “knowing agreement.”  If the study includes minor participants 
who reach the age of majority during the study, as recognized under local law, they must 
reconsent as adults to remain in the study.  If the enrollment of emancipated minors is 
permitted by the study age criteria, the IRB/EC, and local law, they must provide 
documentation of legal status to give consent without the permission of a parent or legal 
guardian.
Before any study-specific activity is performed, the investigator, or a person designated by 
the investigator, will obtain written informed consent from each maternal participant and her 
parent(s)/legal guardian (if a minor).  This will include written informed consent for the 
mother and the fetus during the pregnancy, and the infant’s continuation in the study after 
delivery.  Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements.
Participants and their parent(s)/legal guardian (if a minor) who are rescreened may be 
required to sign a new ICD as per IRB, local regulations, etc.
If during the study, the investigator determines that the maternal participant is for any reason 
no longer capable of providing informed consent, the infant’s continued participation in the 
study requires consent to be obtained from the parent(s)/legal guardian as determined by 
local regulations, legal requirements, and the IRB/EC.
Note: For the infant participant, the term parent(s)/legal guardian denotes the “legally 
authorized representative.”
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10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT)/Clinical Trial Information System (CTIS), and/or www.pfizer.com, and 
other public registries in accordance with applicable local laws/regulations.  In addition, 
Pfizer reports study results outside of the requirements of local laws/regulations pursuant to 
its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted.  These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT/CTIS
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements.
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www.pfizer.com
Pfizer posts clinical study report (CSR) synopses and plain language study results summaries 
on www.pfizer.com for Pfizer-sponsored interventional studies at the same time the 
corresponding study results are posted to www.clinicaltrials.gov. CSR synopses will have 
personally identifiable information anonymized.
Documents Within Marketing Applications 
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized.
Data Sharing
Pfizer provides researchers secure access to participant-level data or full CSRs for the 
purposes of “bona-fide scientific research” that contribute to the scientific understanding of 
the disease, target, or compound class.  Pfizer will make data from these trials available 
24 months after study completion.  Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations.  CSRs will have personally identifiable 
information anonymized.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
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Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan/contracts.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
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Definition of what constitutes source data can be found in the site Source Data Agreement 
Plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study 
(or study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
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The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements.
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
For maternal immunization clinical studies conducted in pregnant women, data on the EDP
including any SAEs/nonserious AEs as well as pregnancy outcomes are collected and 
analyzed in the clinical database. All SAEs are reported to Pfizer Safety using the Vaccine 
SAE Reporting Form. In case of a new pregnancy in a maternal participant before the end of 
the study, any exposure to the investigational product is reportable to Pfizer Safety within 
24 hours of investigator awareness using the Vaccine SAE Reporting Form/EDP 
supplemental form.
The term “participant” in this section refers to (1) the maternal participant and her fetus; and 
after delivery (2) the maternal participant and (3) the infant participant.
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10.2.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.
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Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, cesarean section, endoscopy, appendectomy): the 
condition that leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.2.2. Newly Diagnosed Chronic Medical Conditions
An NDCMC is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
10.2.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting.  Complications that occur during hospitalization are AEs.  If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious.  When in 
doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
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d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a Pfizer 
product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited 
cases by pharmacovigilance personnel.  Such cases are also considered for reporting as 
product defects, if appropriate.
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10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording safety events on the CRF and 
for reporting safety events on the Vaccine SAE Reporting Form to Pfizer Safety.  These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and 
(3) occupational exposure.
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE 
Reporting Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study via 
occupational exposure
Occupational exposure is 
not recorded.
Occupational exposure 
(regardless of whether 
associated with an AE)
Note:  Include all AEs/SAEs 
associated with occupational 
exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.
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AE and SAE Recording/Reporting

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING
to describe the maximum intensity of the AE. For purposes of 
consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent
intervention indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.
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Assessment of Causality

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused the 
event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible.  This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any anonymized 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.
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Follow-up of AEs and SAEs

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.2.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
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are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT values 
>2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
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hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of
reasonable investigations have been received and have excluded an alternative etiology.
10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with International 
Organization for Standardization (ISO) 14155.
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.4.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational medical device.  
This definition includes events related to the investigational medical device or 
comparator for study participants, users, and other persons.  This definition also 
includes events considered related to procedures for study participants only.

An ADE is defined as an AE related to the use of an investigational medical device.  
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
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10.4.2. Definition of Serious Adverse Event, Serious Adverse Device Effect, and 
Unanticipated Serious Adverse Device Effect
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is an AE that:
a. Led to death.
b. Led to serious deterioration in the health of the participant, that either resulted 
in:

A life-threatening illness or injury.  The term “life-threatening” in the definition of 
serious refers to an event in which the participant was at risk of death at the time of 
the event. It does not refer to an event that hypothetically might have caused death, 
if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
SADE Definition

A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE.
Unanticipated Serious Adverse Device Effect (USADE) Definition

A USADE is a serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis management 
file.
10.4.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance.  Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
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10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator 
to review all documentation (eg, hospital progress notes, laboratory reports, and 
diagnostic reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information in 
the participant’s medical records, in accordance with the investigator’s normal clinical 
practice and on the appropriate form of the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of following the reporting process described in the IP 
manual.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
“severe” should not be confused with an SAE. “Severe” is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as “severe.”

An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as “severe.”
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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE/device deficiency.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the medical 
notes that he/she has reviewed the AE/SAE/device deficiency and has provided an 
assessment of causality.

There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE/SAE/Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE/SAE/ device deficiency as fully as 
possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally completed CRF.
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Follow-up of AE/SAE/Device Deficiency

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.4.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.4.6. Reporting of SADEs
SADE Reporting to Pfizer Safety
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.
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10.5. Appendix 5: Background Factors
1. Information on the following will be collected at Visit 1, Visit 4 (12-Month), and 
Visit 6 (24-Month) for all infant participants:

Educational level of parent(s) or legal guardian(s).

Exposure to smoke (including tobacco smoke).

Number of persons in the household ≥18 years of age.

Number of children <18 years of age in the household and if they attend school/ 
daycare.
o
Number of children in the household under 5 years of age (under 60 months).
o
Number of children in the household ≥5 years of age (≥60 months).
2. Information on the following will be collected at each postbirth visit:

Childcare/daycare (for infant participants).

Breastfeeding information (including whether or not breastfeeding is exclusive).
3. Information on the following will be collected at each RTI study visit:

Number of missed days of work for parent(s) or legal guardian(s) due to the infant 
participant’s illness.
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria Checklist 
for MA-RTI Visit – Infant Participants
When an infant MA-RTI medical visit criterion is met or confirmed, the site will obtain 
records from the medical visit and capture the healthcare information as detailed below in the 
eCRF. This information is based on respiratory-related assessments including examination 
findings, clinical findings, and any pathogen-related assessments/findings.
Medical Visit - Visit Details and Assessment Requirements
Note: This should not be linked to a study visit but may overlap with the RTI study visit. 
The following fields and clinical assessment details should be obtained from relevant 
records for the medically attended event prior to each RTI study visit to support the 
assessment of the RTI event.

Reason for visit including date/time, eg,
o
Nasal discharge for 24 hours or more.
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o
Difficulty breathing, labored breathing, or rapid breathing for any duration.
o
Cough.
o
Inability to feed for any duration due to respiratory symptoms.
o
Apnea.
o
Any other respiratory symptom of concern.

Location of medical visit (inpatient clinic, outpatient clinic, emergency department, 
urgent care, hospitalization, home visit, other). Note: study visits should NOT be 
recorded here.
o
If hospital visit, was this triggered by an RTI (include details pertaining to duration
as well as admission and discharge information and records)?

Clinical findings pertaining to respiratory symptoms and/or RTI, as detailed below but 
not limited to:
o
Presence or absence of pertinent examination findings, eg, apnea (documented as per 
chart), wheezing, fever, cough, nasal congestion, intercostal retractions, lower chest 
wall indrawing, grunting, crackles, decreased breath sounds, other abnormal breath 
sounds, dry mucous membranes, skin tenting, sunken fontanelle, difficulty feeding, 
failure to respond/unconsciousness, etc.
o
Respiratory rate from highest/worst value of visit.
o
Oxygen saturation (SpO2) from lowest/worst value of visit.
o
Oxygen supplementation (assisted ventilation, including type of respiratory assistance 
[respirator, “state-of-the-art” occlusive nasal prongs, face tent, etc.]).

Days of supplementary oxygen.

Use of nasal cannula.

Use of high-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive).
o
Heart rate from worst value of visit when performed consistently.
o
Body weight from the date of the MA-RTI event.
o
Temperature from worst value of visit when performed consistently.
o
Additional clinical or respiratory related assessments including chest x-ray.
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
Local test results for RSV as part of routine clinical care:
o
Testing platform used (clinical list of all platforms and validated by research).
o
Result (list: positive, negative, indeterminate, other).

Results for any local non-RSV respiratory pathogen testing conducted as part of routine 
clinical care:
o
Result (list: detected, not detected, indeterminate)

Record the provider diagnosis, including any causative pathogen (if applicable), eg, RSV 
bronchiolitis, asthma, influenza, etc.

Obtain details of all prescribed medications including IV fluid usage.

Obtain details of all AEs/SAEs in line with study requirements. Note: MA-RTIs are not 
AEs/SAEs, unless related to the investigational product or resulting in death.
10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
10.7.1. Informed Consent for the Maternal Participants <20 Years Old
Informed consent for maternal participants <20 years old and their infant participants will be 
obtained based on current Japanese civil code article 753 until 01 April 2022.

Married maternal participants 16 to <20 years of age are deemed to have reached 
“majority” and each maternal participant will sign the ICD for her and her infant’s study 
participation.

The maternal participants 16 years of age and unmarried maternal participants 16 to 
20 years of age are deemed “minors.”

When the maternal participant is a minor under local law, the investigator, or a person 
designated by the investigator, will obtain written informed consent from the maternal 
participant’s legally acceptable representative, parent(s), or legal guardian as well as 
the maternal participant’s assent (affirmative agreement) for her and her child’s study 
participation before any study-specific activity is performed. The investigator will 
retain the original of each signed consent and assent document.
o
The assent form for a minor must be in compliance with ICH GCP, local
regulatory requirements, and legal requirements, including applicable privacy 
laws.
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o
The assent form for a minor used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB before use, and available for 
inspection.
o
The investigator must ensure that the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian is fully informed about the nature and 
objectives of the study and possible risks associated with participation.
o
The source documents must record that the maternal participant was a minor at 
the time of signing the ICD, how the investigator determined that the person 
signing the consent was the maternal participant’s legally acceptable 
representative, the consent signer’s relationship to the maternal participant 
(eg, parent), and that the maternal participant’s assent was obtained.

When the minor maternal participants reach the age of majority during the study, as 
recognized under local law, they must reconsent as adults to remain in the study.

Beginning on 01 April 2022, when the amended civil law in which individuals 18 years 
of age and older are deemed to have reached majority and marriage age for women is 
implemented:

The investigator, or a person designated by the investigator, will obtain written informed 
consent from the maternal participant 18 to <20 years of age and married maternal 
participants 16 to <18 years of age.

For all maternal participants <16 years of age and unmarried maternal participants 16 to 
<18 years of age, the investigator, or a person designated by the investigator, will obtain 
written informed consent from the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian as well as the maternal participant’s assent.
10.7.2. Temperature Measurement and Definition of Fever

Axillary temperature will be measured at Visit 1 and as required at an unscheduled visit 
and will be measured by the maternal participants for 7 days following vaccination.

For the maternal participants enrolled in Japan, an axillary temperature of ≥37.5°C
(99.5°F) meets the definition of a current febrile illness in the criteria for temporarily 
delaying vaccine administration described in Section 5.2.3.

For the purpose of recording the temperature in the e-diary, fever is defined as an axillary
temperature of ≥38.0°C (100.4°F) for maternal participants enrolled in Japan.
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants
As Study C3671008 is a first-in-Japanese study and in accordance with a recommendation 
from the Pharmaceuticals and Medical Devices Agency (PMDA), the study will utilize a 
sentinel cohort for the maternal participants enrolled in Japan with progression to study 
enrollment at all study sites after a safety review (data from each maternal participant 
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through 14 days after vaccination).  In addition to the study procedures and requirements 
specified in the protocol for Study C3671008, the following procedures will be required for 
the maternal participants enrolled in the sentinel cohort in Japan.
10.7.3.1. Enrollment of Maternal Participants in the Sentinel Cohort
In the sentinel cohort, approximately 8 maternal participants will be enrolled.  No more than 
4 maternal participants per day can be randomized.  Vaccination of the remaining maternal 
participants in the sentinel cohort will commence no sooner than 48 hours after the fourth 
participant received her vaccination.
10.7.3.2. Conclusion of the Sentinel Cohort
After enrollment in the sentinel cohort is completed, the Pfizer internal review committee 
(IRC) will review at least 14 days of postvaccination safety data from all maternal 
participants enrolled in the sentinel cohort, including all local reactions, systemic events, and 
AEs.  An acceptable review will trigger an expansion of study enrollment to all study sites in 
Japan. Refer to the IRC charter for further details.
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or Telephone; 14 to 16 Days 
After Vaccination)
All maternal and infant participants enrolled in this study will follow the protocol for 
Study C3671008.  In addition, the maternal participants enrolled in the sentinel cohort in 
Japan will have a Day 15 follow-up visit conducted either at the study site or via telephone.  
This visit should be conducted 14 to 16 days after vaccination.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given since the last visit.

Review the participant’s e-diary data.

Record details of any MA-RTI, including the diagnosis.

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

The investigator or an authorized designee completes the CRF.
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
Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6.

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit.
10.7.3.4. Schedule of Activities for Maternal Participants Enrolled in the Sentinel 
Cohort in Japan
The following table provides an overview of the protocol visits and procedures for the 
maternal participants enrolled in the sentinel cohort in Japan.  Refer to Section 1.2.3.1 for 
the Schedule of Activities for the Maternal Participants: RTI Surveillance for Medically 
Attended Respiratory Tract Illness Visits (Vaccination Until the End-of-Study Visit).
Visit Description
Screening 
and 
Vaccinationa
Day 15 
Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month 
Postdelivery
Visit Window (Days)
28 Days Prior 
to 
Vaccination 
to Day 1
14 to 16 Days
After 
Vaccination
28 to 42 Days
After 
Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity 
Unit
Clinic, Home, or 
Telephone
Informed consent for maternal 
participant and her infant
X
Assign single maternal participant 
identifier 
X
Demography
X
Medical history including obstetric 
historyd
X
Record current/former alcohol, 
tobacco, marijuana, or any illicit drug 
usage
X
Record vital signs
X
Targeted physical and obstetric 
examination performed on the same 
day or within 7 days before the 
vaccination visit
X
Record details of any antenatal and/or 
postnatal steroid treatment, 
monoclonal antibodies, blood 
products, or Rho(D) immune globulin
X
X
X
X
X
Record details of the maternal 
participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
X
Review eligibility criteria
X
X
X
X
Review temporary delay criteria
X
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Visit Description
Screening 
and 
Vaccinationa
Day 15 
Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month 
Postdelivery
Visit Window (Days)
28 Days Prior 
to 
Vaccination 
to Day 1
14 to 16 Days
After 
Vaccination
28 to 42 Days
After 
Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity 
Unit
Clinic, Home, or 
Telephone
Prevaccination blood draw for 
serologic assessment (~15 mL) on the 
same day or within 7 days before the 
vaccination visit
Xe
Assign randomization and container 
number
X
E-diary training, dispense digital 
thermometer and measuring devicef
X
Obtain and record baseline 
assessment of prespecified systemic 
events on the day of and prior to 
vaccination in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 
30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic 
assessment 
(~15 mL)
Xe
Record pregnancy outcome 
information
X
Review e-diary datag
X
X
Record AEs, as appropriateh
X---------------------------------------------X
Record SAEs, as appropriateh
X
X
X
X
X
Record details pertaining to MA-RTI 
visiti
Assessment of confirmed MA-RTI events during the study as detailed in 
Section 1.2.3.1 of the schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = 
intrapartum antibiotic prophylaxis; ICD = informed consent document; MA-RTI = medically attended 
respiratory tract illness.
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Visit Description
Screening 
and 
Vaccinationa
Day 15 
Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month 
Postdelivery
Visit Window (Days)
28 Days Prior 
to 
Vaccination 
to Day 1
14 to 16 Days
After 
Vaccination
28 to 42 Days
After 
Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity 
Unit
Clinic, Home, or 
Telephone
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization 
assessments and test results to confirm maternal participant eligibility for this clinical trial can be obtained a
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation 
and collection of AEs and SAEs through 28 days after vaccination must occur even if delivery occurs 
within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge 
following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal 
standard of care, perform an ultrasound examination. As part of the obstetric history, details regarding the 
last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported 
in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital 
thermometer for recording daily temperatures and will be provided with instructions on their use. 
Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) 
a baseline assessment of prespecified systemic events on the day of and prior to vaccination and 
reactogenicity events from Day 1 to Day 7 following vaccination (where Day 1 is the day of vaccination).  
Remind maternal participants that the study staff/field worker may contact them to obtain additional 
information on events entered into the e-diary.  Ask maternal participants to contact the investigator or 
site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 following vaccination, to 
determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal 
participant may be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to 
evaluate maternal participant compliance and as part of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 
28 days after vaccination.  From the signing of the ICD until the maternal participant completes the study, 
all SAEs will be collected.  Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the 
schedule of assessments in Section 1.2.3.1. These events will not be captured as safety events, unless the 
investigator or an appropriate designee deems them to be related to the investigational product or to have 
resulted in death.
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10.7.4. Exclusion Criterion 12 Clarification
For exclusion criterion 12, “Current alcohol abuse or illicit drug use. Note: Marijuana use is 
not considered an exclusion criterion for the study when elicited in participant screening, 
though it may be considered illicit in some locales.” In Section 5.2.1, any current use of an 
illicit drug including marijuana will not be permitted for maternal participants enrolling from 
study sites in Japan.
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and Unanticipated SAE
Caused by Medical Device
Definition of SAE caused by medical device:
An SAE caused by medical device is defined as an AE caused by a medical device which led 
to an outcome characteristic to SAEs, or a device-related incident whose recurrence might 
lead to death or serious deterioration in health.
NOTE: See the Medical Device Adverse Events, Adverse Device Effects, Serious Adverse 
Events, and Device Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting section (Appendix 4). Deficiencies fulfilling the definition of an 
AE/SAE will also follow the processes outlined in Section 8.3.3 and Appendix 2 of the 
protocol.
10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix – Applicable 
to the Philippines, Gambia, and South Africa Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Participants who have not had ultrasound assessments to determine eligibility during 
routine care should be consented and have an ultrasound within 90 days prior to 
vaccination in order to comply with inclusion criteria #1 in Section 5.1.1.
Safety endpoints:
The time period and frequency for collecting AE and SAE information by the investigator 
and site staff should follow Appendix 2, with the exception of the additional screening 
window for sites conducting ultrasounds procedures from -90 to -28 days. At these sites, the 
safety reporting periods should be as follows:

AEs occurring up to 48 hours after ultrasound assessment that the investigator deems are 
related to the study procedure must be reported in the CRF.

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

The active collection period for nonserious AEs begins 28 days prior to vaccination and 
continues through a minimum of 28 calendar days after vaccination as described in
Section 8.3.1 and Section 10.2.
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MA-RTI endpoints:
Maternal MA-RTIs are collected from the time of vaccination to the end of the study period 
as described in Section 8.1.2.
Note: For maternal participants who are screen failures, the active collection period ends 
when screen failure status is determined.
10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to South 
Korea and Taiwan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Section 5.1.1: Inclusion criterion 1 states that healthy women ≤49 years of age who are 
between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an 
uncomplicated, singleton pregnancy, who are at no known increased risk for complications 
are eligible for the study.
Please find below country-specific minimum age requirements for study entry into the 
protocol:

In South Korea, the minimum age requirement of maternal participants who can be 
enrolled into the study is ≥19 years of age.

In Taiwan, the minimum age requirement of maternal participants who can be enrolled 
into the study is ≥20 years of age.
10.10. Appendix 10: Country-Specific Appendix – Applicable to South Korea Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Exclusion Criterion 12 Clarification
For exclusion criterion 12, “Current alcohol abuse or illicit drug use.  Note: Marijuana use is 
not considered an exclusion criterion for the study when elicited in participant screening, 
though it may be considered illicit in some locales.”  In Section 5.2.1, any current use of an 
illicit drug, including marijuana, will not be permitted for maternal participants enrolling 
from study sites in South Korea.
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10.11. Appendix 11: Country-Specific Appendix – Applicable to the Philippines Only
The following supplementary text should be read in conjunction with the C3671008 protocol
Section 10.1, Appendix 1 requirements, which details the Regulatory, Ethical, and Study 
Oversight Considerations, including the compensation/reimbursement requirements for study 
participants.
Study participants enrolled in the Philippines may be compensated to cover expenses related 
to completion of maternal and infant study visits in accordance with country-specific
applicable laws and regulations, as approved by the IRB/EC. In addition, compensation may 
be provided upon e-diary completion with the approval of the IRB/EC.
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10.12. Appendix 12: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ADE
adverse device effect
AESI
adverse event of special interest
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
Apgar
appearance, pulse, grimace, activity, and respiration
AST
aspartate aminotransferase
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
Clinical Laboratory Improvement Amendments
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EAC
endpoint adjudication committee
EACC
endpoint adjudication committee charter
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
E-DMC
external data monitoring committee
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine
GA
gestational age
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Abbreviation
Term
GBS
group B streptococcal
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBIG
hepatitis B immune globulin
HBV
hepatitis B virus
HCP
healthcare provider
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IAP
intrapartum antibiotic prophylaxis
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
Ig
immunoglobulin
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ISF
investigator site file
ISO
International Organization for Standardization
IUI
intrauterine insemination
IV
intravenous
IWR
interactive Web-based response
LFT
liver function test
LMIC
lower- and middle-income country
LMP
last menstrual period
LRTI
lower respiratory tract illness
MA-LRTI
medically attended lower respiratory tract illness
MA-RTI
medically attended respiratory tract illness
MCAR
missing completely at random
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NAAT
nucleic acid amplification technology
NDCMC
newly diagnosed chronic medical condition
PCD
primary completion date
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Abbreviation
Term
PCR
polymerase chain reaction
PFS
prefilled syringe
PMDA
Pharmaceuticals and Medical Devices Agency
PT
prothrombin time
RAD
reactive airway disease
RCDC
reverse cumulative distribution curve
RSV
respiratory syncytial virus
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RTI
respiratory tract illness
RT-PCR
reverse transcription–polymerase chain reaction
SAE
serious adverse event
SADE
serious adverse device effect
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SMS
short message service
SoA
schedule of activities
SOP
standard operating procedure
SpO2
oxygen saturation
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Tdap
tetanus, diphtheria, and acellular pertussis vaccine
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VE
vaccine efficacy
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11. REFERENCES
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2
Hall CB, Weinberg GA, Blumkin AK, et al. Respiratory syncytial virus–associated 
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3
Shi T, McAllister DA, O’Brien KL, et al. Global, regional, and national disease burden 
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4
Scheltema NM, Gentile A, Lucion F, et al. Global respiratory syncytial virus-associated 
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5
Parikh RC, McLaurin KK, Margulis AV, et al. Chronologic age at hospitalization for 
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6
American Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis 
Guidelines Committee. Policy statement—updated guidance for palivizumab 
prophylaxis among infants and young children at increased risk of hospitalization for 
respiratory syncytial virus infection. Pediatrics 2014;134(2):415-20.
7
Blanken MO, Rovers MM, Molenaar JM, et al. Respiratory syncytial virus and recurrent 
wheeze in healthy preterm infants. N Engl J Med 2013;368(19):1791-9.
8
Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk 
of wheeze and allergy by age 13 years. Lancet 1999;354(9178):541-5.
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Weber MW, Mulholland EK, Greenwood BM. Respiratory syncytial virus infection in 
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Glezen WP, Taber LH, Frank AL, et al. Risk of primary infection and reinfection with 
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American Academy of Pediatrics. Respiratory syncytial virus. In: Kimberlin DW, Brady 
MT, Jackson MA, Long SS, eds. Red book: 2018 report of the Committee on Infectious 
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Prescott WA Jr, Doloresco F, Brown J, et al. Cost effectiveness of respiratory syncytial 
virus prophylaxis: a critical and systematic review. Pharmacoeconomics
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Synagis [prescribing information]. Gaithersburg, MD: MedImmune LLC; 2017.
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14
Munoz FM, Ralston SL, Meissner HC. RSV recommendations unchanged after review 
of new data. AAP News 19 Oct 2017. Available from: 
http://www.aappublications.org/news/2017/10/19/RSV101917. Accessed 15 Nov 2018.
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The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus 
monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection 
in high-risk infants. Pediatrics 1998;102(3):531-7.
16
Baker CJ, Carey VJ, Rench MA, et al. Maternal antibody at delivery protects neonates 
from early onset group B streptococcal disease. J Infect Dis 2014;209(5):781-8.
17
Dangor Z, Kwatra G, Izu A, et al. Correlates of protection of serotype-specific capsular 
antibody and invasive group B Streptococcus disease in South African infants. Vaccine
2015;33(48):6793-9.
18
Scuff TH, Blain AE, Watt J, et al. Impact of the US maternal tetanus, diphtheria, and 
acellular pertussis vaccination program on preventing pertussis in infants <2 months of 
age: A case-control evaluation. Clin Infect Dis 2017;65(12):1977-83.
19
Baxter R, Bartlett J, Fireman B, et al. Effectiveness of vaccination during pregnancy to 
prevent infant pertussis. Pediátrica 2017;139(5):e20164091.
20
Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and 
protection of their infants. N Engl J Med 2014;371(10):918-31.
21
Benowitz I, Esposito DB, Gracey KD, et al. Influenza vaccine given to pregnant women 
reduces hospitalization due to influenza in their infants. Clin Infect Dis 
2010;51(12):1355-61.
22
Forbes ML, Kumar VR, Yogev R, et al. Serum palivizumab level is associated with 
decreased severity of respiratory syncytial virus disease in high-risk infants. Hum 
Vaccin Immunother 2014;10(10):2789-94.
23
Schmoele-Thoma B, Falsey AR, Walsh EE, et al. Phase 1/2, first-in-human study of the 
safety, tolerability, and immunogenicity of an RSV prefusion F-based subunit vaccine 
candidate [poster 2755]. Poster presented at IDWeek; 02-06 Oct 2019; Washington, DC.
24
Pichichero ME, Rennels MB, Edwards KM, et al. Combined tetanus, diphtheria, and 
5-component pertussis vaccine for use in adolescents and adults. JAMA 2005; 
293(24):3003-11.
25
Block SL, Nolan T, Sattler C, et al. Comparison of the immunogenicity and 
reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 
18) L1 virus-like particle vaccine in male and female adolescents and young adult 
women. J Pediatr 2006; 118(5):2135-45.
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26
European Medicines Evaluation Agency (EMEA). Scientific discussion. Gardasil. In: 
European Public Assessment Report (EPAR). London, England: European Medicines 
Agency; 2006: 40 pages.
27
Straňák Z, Saliba E, Kosma P, et al. (2016) Predictors of RSV LRTI Hospitalization in 
Infants Born at 33 to 35 Weeks Gestational Age: A Large Multinational Study (PONI). 
PLoS One 11(6): e0157446.doi:10.1371/journal.pone.0157446.
28
Gilbert W, Jandial D, Field N, et al. Birth outcomes in teenage pregnancies. J Matern 
Fetal Neonatal Med 2004;16(5):265-70.
29
McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer 
bound to a prefusion-specific neutralizing antibody. Science 2013;340(6136):1113-7.
30
Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants 
despite prior administration of antigenic inactivated vaccine. Am J Epidemiol
1969;89(4):422-34.
31
Graham BS. Biological challenges and technological opportunities for respiratory 
syncytial virus vaccine development. Immunol Rev 2011;239(1):149-66.
32
Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial 
virus purified fusion protein-2 vaccine in pregnant women. Vaccine 2003;21(24):3465-7.
33
Madhi SA, Polack FP, Piedra PA, et al. Respiratory syncytial virus vaccination during 
pregnancy and effects in infants. N Engl J Med 2020;383:426-39.
34
Regen AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization 
during pregnancy in 4 high-income countries, 2010–2016.  Clin Infect Dis 
2018;67(12):1915-8. Available from: https://doi.org/10.1093/cid/ciy439. Accessed: 
25 Nov 2019.
35
Pettker CM, Goldberg JD, El-Sayed YY, et al. Committee opinion number 700: methods 
for estimating the due date. Obstet Gynecol 2017;129(5):e150-54.
36
European Commission. Ethical considerations for clinical trials on medicinal products
conducted with minors. 18 Sep 2017. Available from:
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/2017_09_18_ethical_consid_ct_with_minors.pdf. Accessed 21 Feb 2019.
37
Centers for Disease Control and Prevention. Metropolitan Atlanta congenital defects 
program. Available from: https://www.cdc.gov/ncbddd/birthdefects/macdp.html. 
Accessed: 09 Jun 2020.
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Document Approval Record
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PPD
PPD

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671008
Final Protocol Amendment 5, 12 January 2022
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CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLINDED,
PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND 
SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F 
SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING 
PREGNANCY
Investigational Product Number:
PF-06928316 
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine 
United States (US) Investigational New 
Drug (IND) Number:
017931
European Clinical Trials Database 
(EudraCT) Number:
2019-002943-85
Protocol Number:
C3671008
Phase:
3
Short Title: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants 
Born to Women Vaccinated During Pregnancy.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original 
protocol
05 December 2019
Not applicable (N/A)
Protocol 
Amendment 1
24 March 2020
PROTOCOL SUMMARY: Clarification text was 
added in various sections of the main body of the 
protocol to match the revisions made to the protocol 
summary.
Throughout: The protocol now contains final 
wording regarding the double-blinded, placebo-
controlled study design and the final dose and 
formulation of the respiratory syncytial virus 
stabilized prefusion F subunit vaccine (RSVpreF). 
This is as a result of the analysis of the safety, 
tolerability, and immunogenicity data from the 
C3671003 maternal Phase 2b trial.
Section 1.2.1 Study Design – Maternal Participants: 
The final dose and formulation of RSVpreF were 
inserted, including the lyophile match for the 
placebo.
Section 1.2.2 Study Design – Infant Participants: The 
text box pertaining to the vaccine group arms was 
deleted. The maternal-infant dyads will be randomly 
assigned in this study. Rationale: Infant participants 
will not be administered the investigational product. 
Therefore, the current placement is potentially 
confusing to readers. 
Section 1.2.3 Schedule of Activities for Maternal 
Participants, Section 5.2.3, and Section 8.10.1: 
Clarification text was added as follows:
o
The immunogenicity blood collection and 
physical examination window requirements 
before vaccination were aligned to provide 
greater logistical convenience for the 
investigational sites with respect to enrolling 
participants into the study.
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Document History
Document
Version Date
Summary of Changes and Rationale
o
The wording for the study objectives pertaining 
to the request for intrapartum antibiotic 
prophylaxis (IAP) details for maternal 
participants with a group B streptococcal (GBS) 
status was revised to be consistent with the study 
procedural objectives, which are to collect GBS 
status and to ascertain whether any medication 
was given for IAP. This resulted in the deletion 
of the text in Section 6.5.3, as this information is 
captured in Section 8.10.3.
o
A reference to the immunogenicity blood draws 
for maternal participants was added to clarify the 
adverse event (AE) reporting requirements for 
events that might occur as a result of study-
related procedures.
Section 1.2.3.1 Schedule of Activities for Maternal 
Participants – Respiratory Tract Illness (RTI) 
Surveillance for Medically Attended Respiratory 
Tract Illness (MA-RTI) Visits: 
o
Details to be collected during an MA-RTI were 
revised.
o
Clarification was added regarding the safety 
reporting requirements for MA-RTI events that 
might occur during the study. 
Section 1.2.4 Schedule of Activities for Infant 
Participants: 
o
Visit flexibility was increased to prioritize 
participant safety and adherence to local 
guidance in the event of a coronavirus disease 
2019 (COVID-19) outbreak or other outbreaks. 
o
The physical examination and vital sign 
assessment windows for the study were aligned 
to provide greater logistical convenience for the 
investigational sites with respect to compliance to 
study protocol requirements.  
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Document History
Document
Version Date
Summary of Changes and Rationale
o
The protocol safety reporting criteria and period 
for adverse events (AEs), serious adverse events 
(SAEs), and newly diagnosed chronic medical 
conditions (NDCMCs) were streamlined.
Section 1.2.4.1 Schedule of Activities for Infant 
Participants: RTI Study Visits During the Study: The 
table was revised, including splitting the schedules of 
activities for unscheduled RTI visits for all infant 
participants into RTI surveillance from birth to 6 
months and RTI surveillance from 6 months to the 
end of the study. The procedures were streamlined 
for these RTI study visits to improve clarity and 
consistency.
Table 1: Clarification has been added as to when a 
study visit is triggered for reported MA-RTI endpoint 
events on the study. Day 1 is the day of the MA-RTI 
visit as detailed in Section 8.11.7.
In addition, clarification has been added as to what 
constitutes the site source for confirmed study 
endpoint criteria, in order to provide the sites 
guidance on what documentation will eventually be 
submitted to the endpoint adjudication committee 
(EAC) for evaluation.
Section 3.1: The exploratory endpoints were revised 
to correspond with the planned statistical analyses of 
RTI events in the pediatric population. This does not 
represent a change to the study design but instead 
better reflects the total statistical analysis plan. 
Section 3.1, Section 3.2, and throughout: To improve 
clarity and ensure consistency, the use of “RSV-
neutralizing antibody titers” has been changed to 
RSV serum neutralizing titers.” This is the sponsor’s 
preference based on what the neutralizing activity 
assay is based upon, and in this case, it is whole 
serum and not just the purified antibodies during 
these immunogenicity assessments.
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Section 3.3, Section 8.1.1.2, Section 8.1.3, and 
Section 10.2: For further clarification, the protocol’s 
safety and endpoint reporting requirements were 
amended to ensure consistency with Pfizer’s updated 
safety reporting requirements for endpoint-defined 
studies.
Section 4.3: The text “availability of these data are 
expected in 2020” was removed as this statement 
does not accurately reflect the current decision-
making process for the dose and formulation 
selection activities for this study. 
Section 5.2.1: Clarification text was added to the 
exclusion criterion for body mass index (BMI) and 
congenital anomalies based on study requirements.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: The 
tetanus, diphtheria, and acellular pertussis vaccine 
(Tdap) administration requirements text was 
modified to describe the timing of vaccinations based 
on data from the C3671004 study, once available. 
This change will better reflect clinical practice and 
will facilitate recruitment of suitable maternal 
participants for the study.
Section 6.1.1, Section 6.1.3, Section 8.4, and Section 
8.10.1: Clarification text was added to address 
investigational product reconstitution volume and 
administration requirements. This change is to ensure 
consistency with the investigational product 
administration documentation for the study.  
Section 7.2: Clarification text was added to address 
the notification process for biological sample 
management in the event of study participant 
withdrawal from the study.
Section 7.3 and Appendix 1 Informed Consent 
Process: Clarification text was added to address 
study retention and data collection requirements for 
the study. In addition, further clarification has been 
added to emphasize the informed consent process 
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during circumstances where the maternal participant 
is no longer able to provide consent but the infant 
participant’s continued participation in the study 
could be retained by the parent(s)/legal guardian as 
per local regulatory, local laws, and local governance 
approval.
Section 8.1.1.1: Clarification text was added to 
provide guidance regarding the midturbinate swab 
processing requirements and the definition of 
acceptable certified/accredited laboratory bodies for 
this process in the study.
Section 8.2.1.1 and Section 8.10.1: The reporting 
requirements for Grade 4 local reactions in the study 
were clarified; the assessment and reporting are 
carried out by the investigators (or appropriately 
qualified designees).
Section 8.3.1.1, Section 8.3.1.2, Section 8.3.5.1, 
Section 8.3.5.2, Section 8.10, and Section 8.11: The 
reporting requirements were clarified for this 
vulnerable patient population with regard to AEs and 
SAEs likely to occur in the study in women with 
gestational age (GA) eligibility criterion between 24 
0/7 and 36 0/7 weeks.
Section 8.3.6: Text was added to address and 
standardize reporting procedures for adverse events 
of special interest (AESIs) for this patient population.
Section 8.3.7 and Appendix 4: Several Pfizer text 
revisions were incorporated regarding device 
deficiencies and the safety reporting requirements for 
this study.
Section 8.10: The immunogenicity blood collection 
and physical examination window requirements 
before vaccination were aligned to provide greater 
logistical convenience for the investigational sites 
with respect to enrolling participants into the study.  
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Section 8.10.1: The prepregnancy BMI text revisions 
in Section 5.2.1 were aligned with the study
assessment requirements for maternal participants at 
screening.
Section 8.10.2, Section 8.10.3, Section 8.10.4, and 
Section 8.10.6: Clarification text was added to the 
MA-RTI reporting requirements for maternal 
participants in the study to provide guidance and 
ensure the investigational sites provide accurate 
information pertaining to these self-reported events.
Section 8.11.1 to Section 8.11.6: Clarification text 
was added (where applicable) to address the 
following study assessments:
o
“Birth weight must be the first birth weight and 
cannot be based on the standard-of-care 
examination” was removed as this statement is 
confusing to the investigational sites. Birth 
weight assessments have now been realigned 
with standard-of-care assessments at the study 
visit to aid compliance with study assessments 
and requirements.
o
Clarification text was added regarding the 
reporting of standard-of-care measurements for 
vital sign assessments. 
o
In addition, the physical examination and vital 
sign assessment windows for the study were 
aligned to provide greater logistical convenience 
for the investigational sites to comply with study 
protocol requirements.  
o
For further clarification, the RTI study visit 
assessment requirements were amended to 
emphasize the difference between the MA-RTI 
visit criteria and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements. 
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Section 8.11.7.1: For further clarification, the RTI 
study visit assessment requirements have been 
amended to emphasize the following:
o
The RTI study visit window, including nasal 
swab collection from the MA-RTI notification 
for the infant participant.
o
Duplicate text was removed pertaining to the 
MA-RTI definition and the signs and symptoms 
of interest pertinent to an RTI study visit. 
o
Guidance regarding the difference between the 
MA-RTI visit and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements.
Section 8.11.8: Clarification text was added to 
address the RTI study visit window, including nasal 
swab collection from the MA-RTI notification for the 
infant participant.
o
For further clarification, the RTI study visit 
assessment requirements have been amended to 
emphasize the difference between the MA-RTI 
visit and the subsequent study visit after the event 
has been reported. This is to improve clarity and 
consistency with the RTI study visit requirements 
and provide guidance to the investigational sites.
Section 9.1.2.1, Section 9.1.2.2, Section 9.4.1, 
Section 9.2, and Section 9.5: Text was added to 
clarify the statistical analysis procedures in line with 
the current revisions.
Appendix 2: Clarification text was added to support 
the safety and pregnancy outcome reporting 
requirements for participants who may experience 
exposure during pregnancy while in the study.
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Appendix 5: Further clarification was added to the 
background factors of interest during the infant’s 
participation in the study. 
Appendix 6: Clarification text was added to the 
examination and treatment criteria checklist for 
reported MA-RTI visits.  This is to ensure there is 
some consistency to the source records provided for 
these events in relation to the protocol requirements.
Throughout: Several changes were made to 
incorporate the replacement of the Clinical Trial 
Serious Adverse Event Report Form (CT SAE 
Report Form) to Vaccine SAE Reporting Form, as 
part of the new vaccine SAE reporting requirements 
for Pfizer. 
Throughout: Minor editorial revisions were 
incorporated as appropriate. 
Protocol 
Amendment 2
26 June 2020
Section 5.1.1: Administrative update was 
incorporated to address the recently added 
Appendices 7 and 8.
Appendix 7: A country-specific appendix was added 
for Japan to address consent/assent issues for minors, 
temperature measurement, definition of fever, and 
enrollment of maternal participants in the sentinel 
cohort for safety monitoring.
Appendix 8: A country-specific appendix was added 
for the Gambia and South Africa to address an 
extension to the screening period for maternal 
participants with regard to GA requirements and 
consent process.
Protocol 
Amendment 3
26 August 2020
PROTOCOL SUMMARY: Added clarification text 
to the exploratory endpoint section for the infant 
participants; changes were made in the protocol 
summary to match the revisions made in the main 
body of the protocol.
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Section 1.2.2: Study Design – Infant Participants: 
Added text to address RSV seasonality and the 
required RTI surveillance periods during the study. 
Rationale: The previous placement was potentially 
confusing to readers. The revisions provide clarity to 
the investigational sites with regard to the RTI 
surveillance follow-up activities.
Section 1.2.3 and Section 1.2.3.1: Added clarification 
text (where applicable) to address the following: 
o
Added “Home or Telephone” to the type of visit 
options allowed for the 6-month-postdelivery 
visit.
o
Added clarification text to the alcohol history 
reporting requirements and included “obstetric” 
in the screening assessment requirements for the 
study.
o
Added “study staff,” as study personnel are 
allowed to collect and report baseline and 
reactogenicity assessments reported during the 
evaluation period.
o
Added clarification text regarding the reporting 
requirements for AEs, SAEs, and MA-RTIs for 
maternal participants.
Section 1.2.4 - Schedule of Activities for Infant 
Participants: 
o
Added “Home” to the type of visit options 
allowed for the 1-month and 6-month follow-up 
visits and added further clarification to the visit 
status during potential COVID-19 pandemic 
situations or other natural disasters. Rationale: 
Infant participant visit options were aligned with 
the maternal participant requirements to allow for 
visit flexibility.
o
For further clarification, the physical examination 
and vital sign assessment expectations at birth 
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and at the 1-month visit were aligned to provide 
greater logistical convenience for the 
investigational sites to comply with study 
protocol requirements.
Sections 1.2.4, 1.2.4.1, 8.1.1, and 8.11 to 8.12:
Added clarification text (where applicable).
o
To address alternate nasal swab collection 
procedures, if needed, during potential 
COVID-19 pandemic situations or other natural 
disasters.
o
Clarification text was added with regards to the 
start of the reporting period for MA-RTI events 
upon the infant’s delivery.  This is to improve 
clarity and consistency with the capturing and 
reporting requirements for MA-RTI events and 
provide guidance to the investigational sites.
Sections 1.2.4.1, 8.11.7.1, 8.11.8, and Appendix 6: 
o
Added temperature and body weight 
measurements for infant participants during study 
RTI visits.
o
For vital sign measurements, especially oxygen 
saturation measurements (where applicable), 
clarification text was added to state that it is 
recommended that the participant not be 
receiving supplemental oxygen at the time of 
measurement.
These updates are to ensure consistency with the 
study RTI assessment visits after a confirmed 
MA-RTI event.
Section 3.1: Added clarification text as follows:
o
Table 1.
Primary and Secondary Endpoint 
Events and Definitions in Infant Participants: For 
further clarification, added descriptive text to the 
table header to address endpoint events listed 
within the table. In addition, made corrections to 
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the overlapping respiratory rate measurements 
provided for some study endpoint events. These 
changes were made to improve clarity and 
consistency with the endpoint reporting and 
evaluation process for the study.
o
For the infant participant exploratory objectives,
added the planned statistical analysis period of
“after 6 months of age” to “all-cause MA-RTIs 
and hospitalizations due to RSV” in the pediatric 
population based on regulatory authority 
feedback from South Korea.
o
Incorporated revisions to align endpoints with 
study duration, specifically MA-LRTIs due to 
RSV A and RSV B, and MA-RTIs associated 
with non-RSV respiratory pathogens.
o
Added clarification text to address the analysis 
plans for the healthcare utilization endpoints.
Section 4.1: For further clarification, added text to 
address the desire to enroll across gestational age.
Section 4.3: Added a brief summary of the safety and 
immunogenicity results from the C3671003 trial to 
support the decision-making process for this study.
Section 5.1.1: Inserted administrative 
update/clarification text with regards to:
o
Participant eligibility guidance documentation 
available within the investigator site file.
o
The informed consent process for maternal 
participants.
Section 5.2.1: Based on study requirements:

Added clarification text to exclusion criterion 7, 
which addresses the investigator’s judgment 
when assessing participant eligibility (maternal 
participant or her fetus) and regional endemic 
conditions during routine maternal care, as per 
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local standards of care and obstetric 
recommendations.

Added clarification text to address illicit drug use 
pertaining to marijuana.
Section 5.2.2: Deleted the infant participants 
exclusionary criterion pertaining to the “receipt of 
investigational or approved monoclonal antibodies 
against RSV.”  This was to provide additional 
clarification to the investigational sites with regards 
to the infant’s eligibility criteria.
Sections 5.2.3, 6.5.1, and 6.5.2: Modified the Tdap 
administration requirements text to describe the 
timing of vaccinations based on recent data from the 
C3671004 study (A Phase 2b, Placebo-Controlled, 
Randomized, Observer-Blind Study to Evaluate the 
Safety, Tolerability, and Immunogenicity of a 
Respiratory Syncytial Virus (RSV) Vaccine When 
Administered Concomitantly With Tetanus, 
Diphtheria, and Acellular Pertussis Vaccine (Tdap) 
in Healthy Nonpregnant Women 18 Through 49 
Years of Age; ClinicalTrials.gov identifier: 
NCT04071158).
Section 6.1.4: Added text to clarify what constitutes 
a medical device with regards to the investigational 
product in this study.
Section 6.5.2: Added text to clarify the tetanus and 
diphtheria vaccine administration requirements 
during the study.
Section 6.5.4: For further clarification, added text to 
address prohibited vaccinations and treatments for 
infant participants.  This is to provide guidance to the 
investigational sites.
Section 6.5.5: Added text to clarify the permitted 
treatments, vaccines, and procedures acceptable to 
infant participants enrolled in the study.
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Sections 8.2.1 to 8.2.1.2 and Section 8.10.1: For 
further clarification, amended the e-diary completion 
requirements to emphasize the different reporting 
and/recording options for reactogenicity events 
should illiterate maternal participants be enrolled in 
the study. This is to improve clarity and consistency 
with the reactogenicity reporting requirements at the 
investigational sites.
Table 6 and Section 8.2.1.3: Based on regulatory 
feedback, provided a description of the intensity 
scale for the reactogenicity event “fever.”
Sections 8.3.1 to 8.3.1.2, Sections 8.3.5.2 to 8.3.8.1, 
and Section 10.2.3: Added clarification text (where 
applicable) to address the following safety-related 
updates and provide guidance to the investigational 
sites:
o
Several Pfizer text revisions were incorporated 
regarding the safety reporting requirements for 
this study.
o
Text was added to clarify the SAE reporting 
timelines for the study and provide guidance 
regarding the evaluation of and assessment 
procedures for congenital anomalies.
Section 8.10.1: For further clarification, aligned the 
study assessment window requirements before 
vaccination to provide guidance and greater logistical 
convenience for the investigational sites with respect 
to enrolling participants into the study.
Section 8.10.3: Added clarification text with regards 
to the reporting requirements for maternal 
participants diagnosed as GBS positive and 
pregnancy outcome information. This is to improve 
clarity and consistency with the reporting 
requirements at investigational sites.
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Section 8.11.1: Added clarification text on how the 
infant participant’s identifier will be assigned for this 
study.
Sections 8.11.1 to 8.11.6: Added clarification 
regarding the reporting of standard-of-care 
measurements for vital sign assessments, 
measurements, and physical examination procedures
(where applicable) to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 9.2 and Section 9.4.1: Modified text to more 
generally describe Type 1 error control procedures 
and refer to the statistical analysis plan (SAP) for 
details.
Section 9.4.3.2: Added clarification regarding the 
planned analyses for the healthcare utilization 
endpoints.
Section 10.2.5: Deleted the “SAE Reporting to Pfizer 
Safety via an Electronic Data Collection Tool” 
section. For consistency, only the Vaccine SAE 
Reporting Form process will be used.
Appendix 6: Added clarification text to the 
microbiological data collection requirements for the 
study based on any pathogen-related 
assessments/findings performed as part of the 
participants routine clinical care. This is to ensure 
there is some consistency to the source records 
provided for these events in relation to the protocol 
requirements and to address regulatory guidance in 
light of the COVID-19 outbreak or other outbreaks.
Appendix 7: Added clarification text to the 
following:
o
Incorporated minor editorial revisions into the 
Schedule of Activities for Maternal Participants 
Enrolled in the Sentinel Cohort in Japan.
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o
Added clarification text to exclusion criterion 12 
regarding the definition of illicit drug use based 
on country-specific requirements.
o
Incorporated clarification text regarding the 
definition of an SAE caused by a medical device.
Appendix 9: Added a country-specific appendix for 
South Korea and Taiwan to address the minimum 
age requirements for maternal participants in each 
country.
Throughout: Incorporated minor editorial revisions 
as appropriate.
Protocol 
Amendment 4
22 March 2021
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made in 
the main body of the protocol.   
Section 1.2.3: Added text to address safety reporting 
requirements during consent/assent for minors 
enrolled as maternal participants in the study. 
Section 2.1: Added text to address the enrollment of 
adolescent menarchal females into the study, ie, no 
lower age limit for maternal participants. This is 
based on recent regulatory feedback regarding the 
study design for RSVpreF evaluation in pregnant 
adolescent females.
Section 3.1 and Section 9.4.1: The secondary and 
exploratory endpoints were revised to correspond 
with the planned statistical analyses of RTI events in 
the pediatric population:
o
Updated secondary objectives pertaining to 
hospitalization and MA-LRTI due to any cause, 
extended the efficacy analysis to be in line with 
the duration of follow-up for infant participants 
during the first year of their participation in the 
study, which is 360 days after birth. 
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o
An additional secondary objective added to 
assess the efficacy of RSVpreF in reducing the 
incidence of MA-LRTI due to RSV.
o
An additional exploratory objective added to 
assess the efficacy of RSVpreF in reducing the 
incidence of MA-RTI, MA-LRTI, and severe 
MA-LRTI in premature infants <37 weeks of 
age. 
These updates are reflected in the statistical section 
of the protocol and do not represent a change to the 
study design but instead better reflect the total 
statistical analysis plan.
Section 4.1: For further clarification, added text to 
address the consent/assent requirements for minors 
enrolled as maternal participants in the study.
Section 4.1 and Section 4.1.2: Given the COVID-19 
pandemic situation, and the variable RSV season, the 
maternal participant sample size on the study may 
need to be increased and enrollment could possibly 
go up to 10,000 maternal participants.
Section 4.4: Added text to clarify the study definition 
for a completed maternal/infant participant in the 
study. 
Section 5.1.1: Added clarification with regards to
inclusion criteria and incorporated administrative 
update:
o
Removed the lower age limit for healthy pregnant 
females likely to be eligible for enrollment in the 
study. This change will facilitate recruitment of 
suitable maternal participants for the study.
o
Allowed the GA determination to be based upon 
the first trimester ultrasound examination alone, 
without the last menstrual period, in countries 
where this is routine. This is to improve clarity 
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and consistency with the GA determination 
requirements at the investigational sites. 
o
Updated criterion 4 regarding fetal anomaly 
ultrasound examination requirements in the 
study. This is to improve clarity and ensure 
consistency with study requirements at 
investigational sites.
Section 5.2.1: Incorporated administrative update and
clarification with regards to:
o
Marijuana use and maternal participant 
eligibility in the study. 
o
The use of licensed COVID-19 vaccines or 
COVID-19 vaccines authorized for temporary 
or emergency use based on regulatory and 
national recommendations in maternal 
participants enrolled into the study.
This was to provide additional clarification to the 
investigational sites with regards to the eligibility 
criteria of maternal participants.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: Due 
to the current COVID-19 pandemic, added text to 
clarify the vaccination delay criteria and nonvaccine 
administration window for maternal participants 
receiving licensed COVID-19 vaccines or 
COVID-19 vaccines authorized for temporary or 
emergency use. This change is consistent with other 
nonstudy vaccines allowed in the study. 
Section 6.3.1, Section 8.1.2, Section 8.2.1 to 
Section 8.2.1.3, Section 8.3, Section 8.3.1, 
Section 8.3.1.2, Section 8.10.1 to Section 8.10.6, and 
Section 10.1.3: Added text to clarify the 
consent/assent requirements during study 
procedures/assessments in the event “a minor” is 
enrolled as a maternal participant. This is to improve 
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clarity and ensure consistency for the investigational 
sites to comply with study protocol requirements.
Section 8.3.8.1: Added text to make the following 
safety-related updates and provide guidance to the 
investigational sites:
o
Incorporated safety reporting text for participants 
who report a positive test result for severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-
2) during the study.
o
Text was added to clarify the AESI reporting 
requirements for the study and provide guidance 
regarding the definition of and categorization of a 
developmental delay in infant participants. 
Section 8.10.1: Incorporated administrative update 
regarding which body systems are deemed 
mandatory and which discretionary during physical 
examination procedures for maternal participants in 
the study. This is to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 8.11.1: Incorporated text regarding the 
reporting of standard-of-care measurements for vital 
sign and physical examination procedures at the 
infant’s birth. This is to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 8.11.7, Section 8.11.8, and Section 8.12: 
Added text to clarify the nasal swab collection 
requirements from infant participants during a 
confirmed MA-RTI episode.  This is to provide 
flexibility and prioritize participant safety during the 
study.
Section 9.3, Section 9.4.2, Section 9.4.3, and 
Section 9.4.3.2: Added text to clarify the statistical 
analysis procedures in line with the current revisions.
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Document History
Document
Version Date
Summary of Changes and Rationale
Appendix 7 and Appendix 9: Removed the lower age 
limit for healthy pregnant females likely to be 
eligible for enrollment into the study. In addition, 
incorporated minor editorial revisions to the 
informed consent document for maternal participants 
enrolled in Japan only. 
Appendix 8: Added the Philippines to the list of 
countries impacted by an extension to the screening 
period for maternal participants with regard to GA 
requirements and consent process.
Throughout: Incorporated minor editorial revisions 
as appropriate.
Protocol 
Amendment 5
12 January 2022
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made in 
the main body of the protocol.
Section 1.1 and Section 3.1: Typographical error 
with the third secondary efficacy endpoint pertaining 
to endpoint adjudication committee (EAC) activities 
was removed to align with the protocoldefined 
procedures and SAP. 
Section 5.2.3: Administrative update to clarify the 
coadministration window requirements for licensed 
COVID-19 vaccines and COVID-19 vaccines 
authorized for temporary or emergency use, based on
evolving regulatory and national guidelines.
Section 6.5.1 and Section 6.5.2: Added text to clarify 
the coadministration requirements for any licensed 
vaccines containing pertussis in maternal participants 
likely to be eligible for the study.
Section 1.1, Section 4.1, Section 9.2, Section 9.4.1, 
and Section 9.5: Modified text to address additional 
interim analyses planned for the study.
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Document History
Document
Version Date
Summary of Changes and Rationale
Appendix 10: Added a country-specific appendix for 
South Korea to address marijuana use and maternal 
participant eligibility in the study. 
Appendix 11: Added a country-specific appendix for 
The Philippines at the request of the Philippine 
Health Research Ethics Board (PHREB) that clarifies 
the compensation/reimbursement requirements for 
participants enrolled in the Philippines based on 
national regulatory laws and recommendations.
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................29
1. PROTOCOL SUMMARY...................................................................................................30
1.1. Synopsis ..................................................................................................................30
1.2. Schematic for Study Participants ............................................................................39
1.2.1. Study Design – Maternal Participants ........................................................39
1.2.2. Study Design – Infant Participants .............................................................40
1.2.3. Schedule of Activities for Maternal Participants........................................41
1.2.3.1. Schedule of Activities for Maternal Participants: RTI 
Surveillance for Medically Attended Respiratory Tract Illness 
Visits (Vaccination Until the End-of-Study Visit) ............................44
1.2.4. Schedule of Activities for Infant Participants.............................................45
1.2.4.1. Schedule of Activities for Infant Participants: Respiratory 
Tract Illness Study Visits During the Study......................................47
2. INTRODUCTION ...............................................................................................................50
2.1. Study Rationale .......................................................................................................51
2.2. Background .............................................................................................................51
2.3. Benefit/Risk Assessment.........................................................................................52
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................53
3.1. Infant Participants ...................................................................................................53
3.2. Maternal Participants...............................................................................................59
3.3. Protocol-Defined Efficacy Endpoints .....................................................................60
4. STUDY DESIGN.................................................................................................................60
4.1. Overall Design.........................................................................................................60
4.1.1. Approximate Duration of Participation for Each Participant .....................62
4.1.2. Approximate Number of Participants.........................................................62
4.2. Scientific Rationale for Study Design.....................................................................62
4.3. Justification for Dose ..............................................................................................62
4.4. End of Study Definition ..........................................................................................64
5. STUDY POPULATION......................................................................................................64
5.1. Inclusion Criteria.....................................................................................................64
5.1.1. Inclusion Criteria – Maternal Participants..................................................64
5.1.2. Inclusion Criteria – Infant Participants.......................................................67
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5.2. Exclusion Criteria....................................................................................................67
5.2.1. Exclusion Criteria – Maternal Participants.................................................67
5.2.2. Exclusion Criteria – Infant Participants......................................................69
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants ................69
5.3. Lifestyle Considerations..........................................................................................70
5.4. Screen Failures ........................................................................................................70
6. STUDY INTERVENTION..................................................................................................70
6.1. Study Intervention(s) Administered........................................................................70
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........70
6.1.2. Placebo........................................................................................................71
6.1.3. Administration............................................................................................71
6.1.4. Medical Devices .........................................................................................71
6.2. Preparation/Handling/Storage/Accountability ........................................................72
6.2.1. Preparation and Dispensing........................................................................73
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................73
6.3.1. Blinding of Study Site Personnel................................................................73
6.3.2. Blinding of the Sponsor..............................................................................73
6.3.3. Allocation to Investigational Product .........................................................73
6.3.4. Breaking the Blind......................................................................................74
6.4. Study Intervention Compliance...............................................................................74
6.5. Concomitant Therapy..............................................................................................74
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................74
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................75
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................75
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................76
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................76
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications –
Infant Participants............................................................................................76
6.6. Dose Modification...................................................................................................76
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6.7. Intervention After the End of the Study..................................................................76
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................77
7.1. Discontinuation of Study Intervention ....................................................................77
7.2. Participant Discontinuation/Withdrawal From the Study.......................................77
7.3. Withdrawal of Consent............................................................................................77
7.4. Lost to Follow-up....................................................................................................78
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................78
8.1. Efficacy Assessments..............................................................................................79
8.1.1. Efficacy Assessments – Infant Participants................................................79
8.1.1.1. Midturbinate Nasal Swab Collection and Testing 
Requirements for Endpoint Confirmation – Infant Participants........80
8.1.1.2. Events for Adjudication and Submission Guidance –
Infant Participants..............................................................................80
8.1.2. Exploratory Efficacy Assessments – Maternal Participants.......................81
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal 
and Infant Participants .....................................................................................82
8.1.4. Immunogenicity Assessments ....................................................................82
8.1.4.1. Total Volume of Blood Collected – Maternal Participants.......82
8.1.4.2. Total Volume of Blood Collected – Infant Participants............82
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant 
Participants ........................................................................................83
8.1.4.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development – Maternal and Infant 
Participants ........................................................................................83
8.1.4.5. Respiratory Pathogens – Infant Participants .............................83
8.1.4.6. Biological Samples – Maternal and Infant Participants............84
8.2. Safety Assessments .................................................................................................84
8.2.1. Participant Electronic Diary – Maternal Participants .................................84
8.2.1.1. Local Reactions – Maternal Participants...................................85
8.2.1.2. Systemic Events – Maternal Participants..................................87
8.2.1.3. Temperature – Maternal Participants ........................................88
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant 
Participants.......................................................................................................89
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8.3. Adverse Events and Serious Adverse Events..........................................................90
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......90
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................92
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................92
8.3.2. Method of Detecting AEs and SAEs ..........................................................93
8.3.3. Follow-up of AEs and SAEs.......................................................................93
8.3.4. Regulatory Reporting Requirements for SAEs...........................................94
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Investigational Product ..........................................................................94
8.3.5.1. Exposure During Breastfeeding ................................................94
8.3.5.2. Occupational Exposure .............................................................94
8.3.6. Cardiovascular and Death Events...............................................................95
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................95
8.3.8. Adverse Events of Special Interest.............................................................96
8.3.8.1. Lack of Efficacy........................................................................96
8.3.9. Medical Device Deficiencies......................................................................97
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........97
8.3.9.2. Follow-up of Medical Device Deficiencies...............................97
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................97
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................98
8.3.10. Medication Errors.....................................................................................98
8.4. Treatment of Overdose............................................................................................99
8.5. Pharmacokinetics ....................................................................................................99
8.6. Pharmacodynamics..................................................................................................99
8.7. Genetics...................................................................................................................99
8.7.1. Specified Genetics ......................................................................................99
8.8. Biomarkers ..............................................................................................................99
8.9. Health Economics .................................................................................................100
8.10. Procedures – Maternal Participants.....................................................................100
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8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to 
Vaccination to Day 1 – Visit 1) .....................................................................100
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After 
Vaccination)...................................................................................................104
8.10.3. Delivery (Maternity Unit).......................................................................105
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 
210 Days After Delivery)...............................................................................106
8.10.5. Unscheduled Reactogenicity Visits........................................................107
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria –
Maternal Participants .....................................................................................109
8.11. Procedures – Infant Participants..........................................................................110
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After 
Birth)..............................................................................................................110
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After 
Birth)..............................................................................................................111
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 
Days After Birth) ...........................................................................................113
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 
Days After Birth) ...........................................................................................114
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days 
After Birth; Infant Participants Born During the First Year of the Study 
Only) ..............................................................................................................115
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 
742 Days After Birth; Infant Participants Born During the First Year of 
the Study).......................................................................................................116
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 
Months After Delivery)..................................................................................117
8.11.7.1. Study Visits Following a Medically Attended RTI –
Hospital, Home, or Clinic Visit.......................................................117
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit 
Criteria ...........................................................................................................119
8.12. Nasal Swab Collection ........................................................................................120
8.13. Communication and Use of Technology.............................................................121
9. STATISTICAL CONSIDERATIONS ..............................................................................122
9.1. Estimands and Statistical Hypotheses...................................................................122
9.1.1. Estimands – Infant Participants ................................................................122
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9.1.1.1. Efficacy ...................................................................................122
9.1.1.2. Immunogenicity ......................................................................123
9.1.1.3. Safety.......................................................................................123
9.1.2. Estimands – Maternal Participants ...........................................................123
9.1.2.1. Immunogenicity ......................................................................123
9.1.2.2. Safety.......................................................................................124
9.2. Sample Size Determination...................................................................................124
9.3. Populations for Analysis .......................................................................................125
9.4. Statistical Analyses ...............................................................................................126
9.4.1. Efficacy Analyses .....................................................................................126
9.4.2. Safety Analyses ........................................................................................129
9.4.3. Other Analyses..........................................................................................130
9.4.3.1. Immunogenicity Analyses.......................................................130
9.4.3.2. Healthcare Utilization Analyses..............................................131
9.5. Interim Analyses ...................................................................................................132
9.5.1. Data Monitoring Committee.....................................................................133
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................134
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............134
10.1.1. Regulatory and Ethical Considerations ..................................................134
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................134
10.1.2. Financial Disclosure ...............................................................................135
10.1.3. Informed Consent Process ......................................................................135
10.1.4. Data Protection .......................................................................................136
10.1.5. Dissemination of Clinical Study Data ....................................................137
10.1.6. Data Quality Assurance ..........................................................................138
10.1.7. Source Documents..................................................................................140
10.1.8. Study and Site Closure............................................................................140
10.1.9. Publication Policy...................................................................................140
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................141
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................142
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10.2.1. Definition of AE .....................................................................................142
10.2.2. Newly Diagnosed Chronic Medical Conditions.....................................143
10.2.3. Definition of SAE...................................................................................143
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs.....................145
10.2.5. Reporting of SAEs..................................................................................147
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......148
10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting............................................150
10.4.1. Definition of AE and ADE .....................................................................150
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device 
Effect, and Unanticipated Serious Adverse Device Effect............................151
10.4.3. Definition of Device Deficiency.............................................................151
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................152
10.4.5. Reporting of SAEs..................................................................................154
10.4.6. Reporting of SADEs...............................................................................154
10.5. Appendix 5: Background Factors........................................................................155
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria 
Checklist for MA-RTI Visit – Infant Participants...................................................156
10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only...............158
10.7.1. Informed Consent for the Maternal Participants <20 Years Old............158
10.7.2. Temperature Measurement and Definition of Fever ..............................159
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants.........159
10.7.3.1. Enrollment of Maternal Participants in the Sentinel 
Cohort..............................................................................................159
10.7.3.2. Conclusion of the Sentinel Cohort ........................................159
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or 
Telephone; 14 to 16 Days After Vaccination).................................160
10.7.3.4. Schedule of Activities for Maternal Participants Enrolled 
in the Sentinel Cohort in Japan........................................................161
10.7.4. Exclusion Criterion 12 Clarification.......................................................164
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and 
Unanticipated SAE Caused by Medical Device ............................................164
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix –
Applicable to the Philippines, Gambia, and South Africa Only..............................165
10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to 
South Korea and Taiwan Only ................................................................................166
10.10. Appendix 10: Country-Specific Appendix – Applicable to South Korea 
Only.........................................................................................................................167
10.11. Appendix 11: Country-Specific Appendix – Applicable to the Philippines 
Only.........................................................................................................................168
10.12. Appendix 12: Abbreviations .............................................................................169
11. REFERENCES ................................................................................................................172
LIST OF TABLES
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants ...............................................................................................53
Table 2.
Endpoint Events and Definitions in Maternal Participants.......................59
Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained....................................................................................................83
Table 4.
Grading Scale for Local Reactions...........................................................86
Table 5.
Grading Scale for Systemic Events ..........................................................88
Table 6.
Ranges for Fever.......................................................................................89
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals 
at an Interim Analysis.............................................................................133
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Indication
Pfizer’s respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSVpreF) 
is a prophylactic vaccine that is being investigated for the prevention of medically attended
RSV-associated lower respiratory tract illness (LRTI) in infants by active immunization of 
pregnant women.
Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given the global burden of disease, maternal immunization offers an attractive 
strategy for infant disease prevention.  Both preclinical studies in animals and interim data 
from a Phase 1/2 study in healthy nonpregnant adults have demonstrated acceptable 
tolerability and safety of RSVpreF.  A robust immune response has also been observed in 
participants from the aforementioned trial. RSVpreF is currently under assessment in healthy 
pregnant women 18 through 49 years of age (Study C3671003: A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blinded Trial to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT04032093).
The safety and tolerability of RSVpreF in pregnant adolescents has yet to be demonstrated. 
Vaccine-elicited immune responses with RSVpreF are expected to be similar in adolescents 
and women based on studies comparing maternal immunization with Tdap and HPV 
vaccination.  Infants born to adolescent mothers are known to be at a higher risk of 
prematurity, an important risk factor for RSV disease. Therefore, pregnant adolescents 
(18 years of age) are an appropriate pediatric population for RSVpreF maternal 
immunization, providing insight toward the efficacy, safety, and tolerability of the vaccine.
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
lower respiratory tract illness (MA-LRTI) in infants.
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Objectives, Estimands, and Endpoints 
Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC): 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants 
born to maternal 
participants receiving 
1 dose of investigational 
product, the percentage 
of participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

Adverse events (AEs) from birth to 
1 month of age.

Serious adverse events (SAEs) and 
newly diagnosed chronic medical 
conditions (NDCMCs):
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants 
enrolled during the first year of 
the study).
Secondary Efficacy Objectives
– Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV. 
Vaccine efficacy (VE), 
defined as the relative risk
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI: 

occurring within 210 days after birth.

occurring within 240 days after birth, 
if the analysis at 210 days meets 
efficacy criteria. 

occurring within 270 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 270 days meets 
efficacy criteria.
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Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of medically attended 
respiratory tract illness 
(MA-RTI) due to RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs 
from vaccination up to 730 days after 
birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 12 months 
of age.
MA-LRTIs due to RSV occurring 361 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth. 
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV in infants after 6 months 
of age.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA--LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population. 
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth. 
To assess the impact of 
RSVpreF on RSV illness based 
on socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
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To assess the effect of RSVpreF 
on healthcare utilization. 
Univariate summaries of healthcare 
utilization variables, which may include 
the following: number and type of 
medical visits, length of hospital stay, 
requirement for mechanical ventilation, 
requirement for respiratory diagnostic 
procedures, requirement for intravenous 
(IV) fluids, requirement for prescriptions, 
and antibiotic use.
To describe the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI,
MA-LRTI, and severe 
MA-LRTI in premature infants 
<37 weeks of age.
MA-RTI, MA-LRTI, and severe 
MA-LRTI due to RSV occurring 0 to 
730 days after birth.
Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimand
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery 
study visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum
neutralizing titers and prefusion F 
immunoglobulin G (IgG) titers 
measured:

before vaccination.

at delivery.
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Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis section [Section 9.2]).  There is no specific case target for 
the additional primary endpoint of severe MA-LRTI. The total enrollment number of 
maternal participants may vary depending on the incidence rate of the primary endpoint in 
the infant participants, the true underlying VE, and a potential early stop for efficacy or 
futility. In the event that efficacy in the infant population is demonstrated at an interim 
analysis, enrollment of maternal participants may continue in order to obtain safety 
evaluations in an adequate number of maternal and infant participants to support vaccine 
registration with national health authorities.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It was anticipated that approximately 
6900 mother-infant pairs would be needed to accumulate 124 per-protocol cases prior to the 
global COVID-19 pandemic.  With the variable RSV season, the sample size may need to be 
increased and enrollment could go up to 10,000 maternal participants based on the number of 
cases of RSV.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF will be 120 µg 
(60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants. Note: Maternal participants 
will include adolescent females who may be referred to as “minors.” 
Information/assessments for minors may require parental/legal guardian 
awareness/approval per local regulations.
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Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study, all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term respiratory 
tract illness (RTI) surveillance and safety oversight to address safety and the possibility of 
conferred enhanced protection (antibody persistence) during a second RSV season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee.
Planned Duration
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on gestational age (GA) at the time of vaccination and 
when the infant is actually born.
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
Data Monitoring Committee
This study will use an external data monitoring committee (E-DMC) to monitor vaccine 
safety and efficacy and study futility.
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Statistical Methods
The primary hypothesis to be tested is that VE with respect to MA-LRTI due to RSV or 
severe MA-LRTI due to RSV in infants within at least 90 days after birth is more than 20%, 
relative to placebo. The 2 primary endpoints will be tested in parallel using a multiplicity 
adjustment procedure. VE will be estimated using the exact conditional binomial method. 
There will also be hierarchical testing of the primary endpoints to 120 days, 150 days, and 
180 days, conditional on success of the analysis for the shorter intervals. Interim analyses of 
the MA-LRTI-due-to-RSV endpoint with the opportunity to stop the study for efficacy or 
futility may be included. At the end of the trial, the RSV vaccine may be deemed efficacious 
if there are 43 or fewer cases of MA-LRTI due to RSV in the RSV vaccine group out of the 
124 total primary-endpoint cases.  This corresponds to estimated VE = 47% with 95.1% 
confidence interval (CI) = (22%, 64%). For severe MA-LRTI, assuming a total of 50 cases 
occur, the vaccine may be deemed efficacious if there are 14 or fewer cases in the RSV 
vaccine group.  This corresponds to estimated VE = 61% with 95.1% CI = (26%, 81%).
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1.2. Schematic for Study Participants
1.2.1. Study Design – Maternal Participants
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1.2.2. Study Design – Infant Participants
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Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
1.2.3. Schedule of Activities for Maternal Participants
Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current/former alcohol, tobacco, marijuana, or any illicit drug 
usage
X
Record vital signs
X
Targeted physical and obstetric examination performed on the same 
day or within 7 days before the vaccination visit
X
Record details of any antenatal and/or postnatal steroid treatment, 
monoclonal antibodies, blood products, or Rho(D) immune globulin
X
X
X
X
Record details of the maternal participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
Review eligibility criteria
X
X
X
Review temporary delay criteria
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Prevaccination blood draw for serologic assessment (~15 mL) on the 
same day or within 7 days before the vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and measuring devicef
X
Obtain and record baseline assessment of prespecified systemic events 
on the day of and prior to vaccination in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic assessment (~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X-------------------------- X
Record AEs, as appropriateh
X-------------------------- X
Record SAEs, as appropriateh
X
X
X
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of the 
schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; 
ICD = informed consent document; MA-RTI = medically attended respiratory tract illness.
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the LMP and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) a baseline 
assessment of prespecified systemic events on the day of and prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination 
(where Day 1 is the day of vaccination).  Remind maternal participants and their parent(s)/legal guardian (if a minor) that the study staff/field worker may 
contact them to obtain additional information on events entered into the e-diary.  Ask maternal participants or their parent(s)/legal guardian (if a minor) to 
contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 following vaccination, to determine if an 
unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal participant may be referred to the appropriate healthcare facility 
at the discretion of the study staff/field worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 28 days after vaccination.  From the signing of 
the ICD until the maternal participant completes the study, all SAEs will be collected. Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
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1.2.3.1. Schedule of Activities for Maternal Participants: RTI Surveillance for Medically Attended Respiratory Tract Illness
Visits (Vaccination Until the End-of-Study Visit)
Visit Description
Assessments of MA-RTIa
Visit Window
As Soon as Possible After Confirmed MA-RTI 
Type of Visit
Telephone
Record details of a confirmed MA-RTI 
X
Details of an acute illness visit AND a report of 1 or more of the following RTI
signs and symptoms: 

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
X
Obtain standard-of-care records, including local NAAT testing results (if 
applicable)b
X
Record nonstudy vaccine information
X
Record AEs and SAEs, as appropriatec
X
Complete the CRF with details 
X
Abbreviations: CRF = case report form; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; 
RSV = respiratory syncytial virus; RTI = respiratory tract illness.
a.
Confirmed cases of MA-RTI will be collected from vaccination until the maternal participant completes the study. The assessment of the event would 
involve a telephone call, or a clinic visit if determined by the investigator to be warranted. 
b.
Site staff will review and collect data pertaining to the illness and any local NAAT testing results (RSV, influenza, etc), if available.
c.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  MA-RTI events will not be captured as safety 
events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to have resulted in death. Please see 
Section 8.3.1 for reporting requirements and timelines.
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1.2.4. Schedule of Activities for Infant Participants
Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Assign infant participant identifier
X
Demography 
X
Collect background factorsc
X
X
X
X
X
X
Collect birth outcome information including 
infant’s birth data and appearance, pulse, grimace, 
activity, and respiration (Apgar) score
X
Obtain and record infant’s length, head 
circumference, and weight
X
X
X
X
(if clinic visit)
X
(if clinic visit)
Physical examination including vital signs
(temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate) performed within 48 hours 
after birth
X
Obtain and record vital signs, including 
temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate
X
Targeted physical examination (record in the site 
source document)
X
X
X
(if clinic visit)
X
(if clinic visit)
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, 
packed cells)
X
X
X
X
X
X
Review eligibility
X
Cord blood sample (~10 mL) for serologic 
assessmentd
X
Record AEs, as appropriatee
X
Record NDCMCs and SAEs, as appropriatee
X
X
X
X
X
X
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Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Surveillance reminder contact
Contact with the infant 
participants’ parent(s) or legal 
guardian(s) approximately 
every week until Visit 3
From Visit 3, contact with the infant participant’s parent(s) or legal guardian(s), 
approximately every 28 to 35 days until the end of the study
Assessment of MA-RTIsf,g
Assessment of MA-RTI events 
during the active RSV 
surveillance period as detailed 
in Section 1.2.4.1 of the 
schedule of activities
Assessment of MA-RTI events as detailed in Section 1.2.4.1 of the schedule of 
activities
Abbreviations: MA-RTI = medically attended respiratory tract illness; NDCMC = newly diagnosed chronic medical condition; 
RSV = respiratory syncytial virus; SpO2 = oxygen saturation.
a.
Applicable only for infant participants enrolled during the first year of the study.
b.
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), study visits that cannot be conducted in the clinic or at home, in 
accordance with the protocol requirements, may be conducted via telephone. 
c.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV illness. 
d.
Cord blood must be obtained on the day of birth. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical cord has 
been clamped and cut. If cord blood is unavailable, a blood sample may be collected from the infant participant preferably within the first 24 hours but up 
to 7 days after birth. The infant’s weight must be used to determine the volume of blood that can be collected.
e.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs, NDCMCs, and SAEs through 28 days after birth.  From 
29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected.  An NDCMC is defined as a disease or medical 
condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
f.
A confirmed MA-RTI is defined as an expected study event based on the assessments detailed in the schedule of assessment in Section 1.2.4.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
g.
Reporting MA-RTI events should commence 72 hours after the infant’s delivery.  Respiratory distress events associated with and within 72 hours of birth 
should not be captured as MA-RTI events on the study but should be captured as AEs/SAEs (if applicable).
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1.2.4.1. Schedule of Activities for Infant Participants: Respiratory Tract Illness Study Visits During the Study 
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Surveillance reminder contact
Contact the infant participants’ parent(s) or 
legal guardian(s) approximately every week 
until Visit 3
From Visit 3, contact the infant participants’ parent(s) or legal 
guardian(s), approximately every 28 -35 days until the end of the 
study
Record confirmed MA-RTI as detailed in Appendix 6, as 
appropriate
X
X
X
Record details of the RTI, including 1 or more of the 
following RTI signs and symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid 
breathing for any duration

Cough

Inability to feed for any duration because of 
respiratory symptoms

Apnea

Any other respiratory symptom of concern 
X
X
X
Obtain standard-of-care records and complete CRFc
X
X
X
Record local NAAT testing results, if performed and 
availabled
X
X
X
Perform RTI study visit, record targeted assessment
results (temperature, heart rate, respiratory rate, SpO2 by 
pulse oximetry, chest wall indrawing) and body weight, and 
collect nasal swab (for RT-PCR)e
X
X
Record concomitant medication associated with the 
treatment of the MA-RTI
X
X
X
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Collect background factors associated with MA-RTIf.
X
X
X
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, packed 
cells)
X
X
X
Record AEs , NDCMCs, and SAEs, as appropriateg
X
X
X
Compile MA-RTI visit source documentation upon 
request by adjudication committee (qualifying 
RSV-positive cases only)
X
X
Abbreviations: CRF = case report form; HCP = healthcare provider; ICU = intensive care unit; IV = intravenous; MA-LRTI = medically attended lower 
respiratory tract illness; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; NDCMC = newly diagnosed 
chronic medical condition; RSV = respiratory syncytial virus; RTI = respiratory tract illness; RT-PCR = reverse transcription–polymerase chain reaction; 
SpO2 = oxygen saturation.
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
a.
If the infant participant is reported to be experiencing or has had an MA-RTI from birth until Visit 3, the site should arrange a study visit as soon as possible 
and within 72 hours (preferable) or up to 10 days. Ideally, the RTI study visit will be conducted at the investigational study site; however, it is possible that 
the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit where the infant 
participant is residing. Note: Reporting MA-RTI events should commence 72 hours after the infant’s delivery.  
b.
If the infant participant is reported to be experiencing or has had an MA-RTI associated with severe LRTI criteria or been hospitalized for an RTI from Visit 
3 until the end of study participation, the site should arrange a visit as soon as possible and within 72 hours (preferable) or up to 10 days of site awareness. 
Ideally, assessment of these potential endpoint events (hospitalization due to RTI or severe MA-LRTI) will be conducted at the investigational study site; 
however, it is possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff 
may visit where the infant participant is residing. Note: For nonsevere MA-RTIs, a telephone contact with the infant participants’ parent(s) or legal 
guardian(s) is acceptable to complete the study visit.
c.
Obtain case records, including details of hospitalization, ICU stays, use of oxygen, IV fluids usage, etc.
d.
The site staff/field worker will review and collect data related to any local NAAT testing results, if performed and available.
e.
The site staff/field worker will collect nasal swabs for confirmed MA- RTIs, including confirmed cases of hospitalizations due to an RTI and severe MA-
LRTIs. In the event that restrictions prevent taking RTI study swabs because of an outbreak, pandemic situation, or natural disaster, the study nasal swab 
can be collected for processing at Pfizer’s central laboratory by the infant caregiver, during or within 10 days following an MA-RTI visit, or by the HCP 
assessing the infant during the MA-RTI visit (in addition to any samples obtained in the course of routine clinical care) as detailed in Section 8.11.7.1 and 
Section 8.11.8.
f.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV. This will be collected for 
all MA-RTI events reported.
g.
The investigator and site staff/field worker will ensure the active elicitation and collection of NDCMCs and SAEs through the end-of-study visit for the 
infant participant. From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected. An NDCMC is defined 
as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma). Note: A 
confirmed MA-RTI will not be captured as a safety event, unless the investigator or an appropriate designee deems it to be related to the investigational 
product or to have resulted in death.
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2. INTRODUCTION
Prevention of RSV disease in young infants is a significant unmet medical need globally.  
RSV is the leading cause of bronchiolitis and viral pneumonia in infants and can lead to fatal 
respiratory distress, especially in those with risk factors including premature infants with 
underlying cardiopulmonary disease, or in the absence of effective healthcare systems.1
However, most cases of RSV disease occur in healthy, full-term infants without risk factors.2
Worldwide, RSV kills approximately 118,200 children annually, with about half of those 
deaths occurring in infants under 6 months of age, and the majority of those occurring in 
resource-limited countries.3,4 In the United States, RSV is the leading cause of infant 
hospitalization, with more than 60,000 hospitalizations of children 12 months of age and 
younger annually.5,6  There is increasing evidence that the link between severe RSV disease 
in infancy and wheezing later in childhood may be causal.7,8  Like influenza, RSV infection 
follows a seasonal pattern, causing illness primarily in the cooler months of the year in 
temperate regions and during the wet season in tropical countries with seasonal rainfall.9  
Infection is essentially universal by the time children reach 2 years of age.10
Currently, there is neither specific treatment for RSV infection nor a vaccine to protect 
against RSV disease.  Treatment consists primarily of supportive care.  A prophylactic 
humanized monoclonal antibody, palivizumab (Synagis, AstraZeneca), targeting the RSV F 
glycoprotein is available for prevention of severe RSV disease in young infants at increased 
risk.11  Limitations of its use include its high cost12 and requirement of multiple monthly 
injections,13 and so it remains recommended for use only in very premature infants and 
others at increased risk of severe illness.6,14
Nevertheless, the protective effect of Synagis provides definitive proof of principle that 
serum neutralizing antibody directed against the F protein can provide clinically meaningful 
protection against RSV lower respiratory tract disease in young infants.15  Furthermore, it is 
well known that in other disease settings, antibodies transferred from mothers to their fetuses 
across the placenta can reduce infant disease early in life,16,17,18,19,20,21 suggesting that 
maternal immunization is a reasonable approach to RSV disease prevention among young 
infants.
There are 2 antigenic variants of RSV, namely, RSV subgroup A (RSV A) and RSV 
subgroup B (RSV B).  The RSV vaccine being investigated in this study is a bivalent vaccine
composed of stable RSV prefusion F antigens representing the 2 subgroups to help ensure the 
broadest coverage against RSV illness.
RSVpreF is a prophylactic vaccine being developed to prevent medically attended
RSV-associated LRTI in infants by active immunization of pregnant women.
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2.1. Study Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given a global burden of disease in the millions of cases each year, maternal 
immunization offers an attractive strategy for infant disease prevention.  Both preclinical 
studies in animals and interim data from a Phase 1/2 study in healthy nonpregnant adults 
have demonstrated acceptable tolerability and safety of RSVpreF.  A robust immune 
response has also been observed in the population of the aforementioned trial, at 1 month 
after vaccination. The combined RSV A and B serum neutralization geometric mean titers 
(GMTs) have been shown to be 12 to 20 times higher than those with 100 μg/mL of
palivizumab, the concentration of the monoclonal antibody that is known to provide near to 
complete protection of high-risk infants from severe RSV disease.22,23 RSVpreF is currently 
under assessment in healthy pregnant women 18 through 49 years of age (Study C3671003, 
A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093).
The safety and tolerability of RSVpreF in pregnant adolescents has yet to be demonstrated. 
Vaccine-elicited immune responses with RSVpreF are expected to be similar in adolescents 
and women based on studies comparing maternal immunization with Tdap and HPV 
vaccination.24,25,26  Infants born to adolescent mothers are known to be at a higher risk of 
prematurity, an important risk factor for RSV disease.27,28 Therefore, pregnant adolescents 
(18 years of age) are an appropriate pediatric population for RSVpreF maternal 
immunization, providing insight toward the efficacy, safety, and tolerability of the vaccine.
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
RSV-associated LRTI in infants.
2.2. Background 
RSV is an important cause of morbidity and mortality worldwide, with a substantial burden 
of disease borne by young infants.  Rates of severe RSV illness are highest in infants 
6 months of age, with a peak in hospitalization between 1 and 2 months of life, though the
highest case-fatality rates are observed in the neonatal period (<1 month).2 Infants born 
prematurely and those with underlying cardiac or pulmonary disease are at further increased 
risk of severe clinical disease due to RSV.  A 2017 retrospective case analysis that examined 
RSV mortality data from 23 countries demonstrates the global nature of the seriousness of 
RSV disease, with significant morbidity and mortality occurring in both lower- and 
middle-income countries (LMICs) and high-income countries.3,4
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No specific treatments for RSV exist, and available prophylactic measures (ie, RSV 
monoclonal antibody) are limited to use in only those infants at highest risk; additionally, in 
LMICs, use of available RSV prophylaxis is cost-prohibitive.  While active immunization 
against RSV in infants might be an option, multiple efforts, extending over half a century, to 
develop a safe and effective RSV vaccine to protect infants from disease have yielded little 
success.  The early peak of disease presents a further obstacle to an active vaccination 
strategy for infants.  Given these challenges, maternal immunization to protect infants early 
in life offers an attractive strategy for infant disease prevention.
The present RSV vaccine efforts were initiated in early 2014 based on a new scientific 
discovery (determination of the RSV prefusion F crystal structure)29 and a changing 
regulatory and policy environment that today supports the development of vaccines for 
maternal immunization to protect very young infants.  The trimeric RSV F surface 
glycoprotein in a prefusion conformation is now known to be the primary target of 
neutralizing antibodies and is the basis for the engineered antigens in Pfizer’s vaccine 
candidate.   Applying structure-guided vaccine design, Pfizer has developed a stabilized RSV 
prefusion F vaccine candidate.  The core hypothesis underlying Pfizer’s RSV vaccine 
development effort for prevention of infant disease is that vaccine antigens based on RSV 
prefusion F, when administered to pregnant women in the second or third trimester of 
pregnancy, will elicit sufficiently high neutralizing antibody titers that, when the antibodies
are actively transferred transplacentally to the fetus, will protect infants against RSV disease. 
The aim is for neutralizing antibody levels to be at sufficient levels such that infants will be 
protected from birth and possibly through their first RSV season.
2.3. Benefit/Risk Assessment
RSVpreF is being evaluated in ongoing clinical studies.  Pfizer’s maternal immunization 
approach circumvents the risk of vaccine-mediated disease enhancement that was observed 
in the 1960s following direct immunization of RSV-naive infants with a formalin-inactivated 
RSV vaccine (FI-RSV).30  FI-RSV elicited a predominantly nonneutralizing antibody 
response and a Th2-biased cell-mediated response, both of which are considered potential 
contributing factors to disease enhancement.31  During preclinical studies, in a standard 
cotton rat infectious RSV challenge model, FI-RSV showed pathological signs of causing 
disease enhancement, and the current Pfizer vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease enhancement has not been reported to occur in 
RSV-experienced individuals after immunization with any RSV vaccine candidate.  Because 
pregnant women are universally RSV-experienced, they are not considered at risk for a 
disease-enhancing immune response to the vaccine that could exacerbate infection in 
themselves.  Enhanced disease has not been observed in infants born to mothers who
received prior investigational RSV vaccines; therefore, enhanced disease in infants is very
unlikely.  A previous study of maternal immunization with a Wyeth (later merged with 
Pfizer) investigational RSV vaccine (PFP-2) showed an acceptable safety profile, even 
though this candidate contained a postfusion RSV F antigen that elicited a relatively weak 
RSV-neutralizing antibody response and a higher nonneutralizing RSV-binding antibody 
response in pregnant women.32  A recently completed Phase 3 maternal RSV trial (Novavax) 
with an RSV vaccine containing F not stabilized in the prefusion form, given to over 
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4600 healthy pregnant volunteers, showed a similar safety profile in the RSV vaccine and 
placebo groups.33
Vaccination with the RSV prefusion F antigens elicits a higher ratio of neutralizing to 
nonneutralizing antibodies, more closely matching the profile in naturally exposed 
individuals.  The safety profile of RSVpreF observed to date is similar to that of prior RSV F 
subunit vaccines tested in RSV-experienced adults.
There are limited data on the global burden of maternal RSV infection, likely in part because 
of infrequent diagnostic testing. However, in one multisite study, RSV-associated disease in 
pregnancy was shown to result in prolonged hospitalization and an increased likelihood of 
preterm birth in women who tested RSV-positive.34 It is possible that vaccination may 
benefit the pregnant women who receive it. RTI in mothers who receive RSVpreF will be 
explored in this study.  The benefit of maternal vaccination is accrued to the infant by means 
of transplacental antibody transfer.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the investigator’s brochure (IB), which is the 
single reference safety document (SRSD) for this study.
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Infant Participants
The study objectives and endpoints for infant participants employ the event definitions in 
Table 1.
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study Endpoints/Assessments
Study Definitions
Medically attended visit
Infant participant has been taken to or seen by a healthcare provider 
(eg, outpatient or inpatient visit, emergency room, urgent care, or home 
visit)
MA-RTI visit for infant 
participant
A medically attended visit AND 1 or more of the following RTI signs and 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any 
duration

Cough

Inability to feed for any duration because of respiratory symptoms

Apnea

Any other respiratory symptom of concern 
RSV-positive testa

RSV RT-PCR–positive test result by Pfizer central laboratory
OR

RSV-positive test result by certified laboratory with NAAT for RSV
MA-RTI due to RSVb

An MA-RTI visit 
AND

RSV-positive test result as described in Section 8.1.1.1
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Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study Endpoints/Assessments
Study Definitions
MA-LRTI due to any cause

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age], 
≥50 bpm for ≥2 months to <12 months of age, or ≥40 bpm for 
≥12 months to 24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
MA-LRTI due to RSVb

Infant with an MA-RTI visit 
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age] or 
≥50 bpm for ≥2 to <12 months of age, or ≥40 bpm for ≥12 months to 
24 months of age) OR

SpO2 <95% OR

Chest wall indrawing 
AND 

RSV-positive test result as described in Section 8.1.1.1
Hospitalized RTI due to RSVb
An RTI due to RSV that results in hospitalization
Severe MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥70 bpm for <2 months of age [<60 days of age], 
≥60 bpm for ≥2 months to <12 months of age, or ≥50 bpm for 
≥12 months to 24 months of age) OR

SpO2 <93% OR

High-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive) OR

ICU admission for >4 hours OR

Failure to respond/unconscious 
AND

RSV-positive test result as described in Section 8.1.1.1
Protocol-defined primary 
endpoint

Any MA-LRTI or severe MA-LRTI due to RSV as determined by an 
EAC
Abbreviations: bpm = breaths per minute; EAC = endpoint adjudication committee; ICU = intensive care unit; 
MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically attended respiratory tract 
illness; NAAT = nucleic acid amplification technology; RR = respiratory rate; 
RSV = respiratory syncytial virus; RTI = respiratory tract illness; SpO2 = oxygen saturation.
a.
RSV-positive testing is defined as a positive RSV test (see Section 8.1.1.1) conducted on a sample 
obtained during the medically attended visit or within 10 days (where Day 1 is the day of the MA-RTI 
visit) as detailed in Section 8.11.7.
b.
The EAC will determine if the endpoint criteria have been met upon review of the site source 
documentation from the MA-RTI visit and RTI study visits, including all available RSV test results.
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Study Objectives – Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI due 
to RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants born 
to maternal participants 
receiving 1 dose of 
investigational product, 
the percentage of 
participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

AEs from birth to 1 month of age.

SAEs and NDCMCs:
o
from birth through 6 months of 
age (first RSV season for all infant 
participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants enrolled 
during the first year of the study).
Secondary Efficacy Objectives –
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV. 
Vaccine efficacy (VE), defined 
as the relative risk reduction of 
the endpoint in the RSV 
vaccine group compared to the 
placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI: 

occurring within 210 days after birth.

occurring within 240 days after birth, 
if the analysis at 210 days meets 
efficacy criteria. 

occurring within 270 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 270 days meets 
efficacy criteria.
Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI due to 
RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs from 
vaccination up to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 12 months of 
age.
MA-LRTIs due to RSV occurring 361 to 
730 days after birth.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI due 
to RSV in infants after 6 months 
of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV in infants after 6 months of 
age.
Hospitalization due to RSV occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI in 
the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
To assess the impact of RSVpreF 
on RSV illness based on 
socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
To assess the effect of RSVpreF 
on healthcare utilization.
Univariate summaries of healthcare 
utilization variables, which may include the 
following: number and type of medical 
visits, length of hospital stay, requirement 
for mechanical ventilation, requirement for 
respiratory diagnostic procedures, 
requirement for IV fluids, requirement for 
prescriptions, and antibiotic use.
To describe the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI, MA-LRTI, 
and severe MA-LRTI in 
premature infants <37 weeks of 
age.
MA-RTI, MA-LRTI, and severe MA-LRTI
due to RSV occurring 0 to 730 days after 
birth.
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3.2. Maternal Participants
The study objectives and endpoints for maternal participants employ the event definitions in 
Table 2.
Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
Maternal medically attended visit
The maternal participant reports a visit with a healthcare 
provider (eg, outpatient or inpatient visit, emergency room, 
urgent care, or home visit)
MA-RTI visit maternal participant
A medically attended visit AND 1 or more of the following 
RTI signs and symptoms:

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
Abbreviations: MA-RTI = medically attended respiratory tract illness; RTI = respiratory tract illness.
Study Objectives – Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimands
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery study 
visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum neutralizing 
titers and prefusion F IgG titers 
measured:

before vaccination.

at delivery.
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3.3. Protocol-Defined Efficacy Endpoints 
All infant participants experiencing an MA-RTI will have an RTI study visit as detailed in
Section 8.1.  This protocol will use an independent EAC to determine whether certain 
investigator-reported events meet the definition of disease-related efficacy endpoints, using 
predefined endpoint criteria as summarized in Table 1. Members of this EAC will be blinded 
to the vaccine assignment to allow for unbiased assessments.
Recognizing that RSV disease is a dynamic illness, sites will be instructed to submit all 
available source documentation for adjudication from the MA-RTI visit and to record data 
from the worst day of illness in the electronic case report form (eCRF).  The EAC will 
determine if the endpoint criteria have been met upon review of the site source
documentation from the MA-RTI visit, including data collected at the RTI study visit, and all 
available RSV testing.  Further information about the EAC will be detailed in the 
adjudication charter, including specific descriptions of the scope of its responsibilities and 
the process and definitions to review and assess study endpoints.
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition and 
constitute a study endpoint will not be recorded as AEs.  For those AEs that are handled as 
disease-related efficacy endpoints, a data monitoring committee (DMC) will conduct 
unblinded reviews on a regular basis throughout the trial (see Data Monitoring Committee,
Section 9.5.1).
Nonendpoint events (eg, an event that is determined not to be an MA-RTI) must be evaluated 
for safety reporting as per the protocol requirements.  Any AE that is adjudicated by the EAC
to not meet any endpoint criteria will be reported back to the investigator site of incidence; 
the investigator at the site must evaluate the event for safety as described in Appendix 2 of 
this protocol.  If the event is classified as serious, the investigator’s SAE awareness date in 
this instance is identified as the date on which the investigator site receives the nonendpoint 
SAE back from the EAC.  Handling these SAEs in this manner will allow Pfizer to meet its 
sponsor reporting obligations to regulatory authorities upon receipt of such SAEs.
Any events that remain unadjudicated at the annual safety report cutoff date will not be 
included in the safety tables of the report.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons. 
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This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of 
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis (Section 9.2). There is no specific case target for the 
additional primary endpoint of severe MA-LRTI. The total enrollment number of maternal 
participants may vary depending on the incidence rate of the primary endpoint in the infant 
participants, true underlying VE, and a potential early stop for efficacy or futility. In the 
event that efficacy in the infant population is demonstrated at an interim analysis, enrollment 
of maternal participants may continue in order to obtain safety evaluations in an adequate 
number of maternal and infant participants to support vaccine registration with national 
health authorities. Enrollment will be monitored to ensure even distribution of vaccination 
across gestational age between 24 0/7 and 36 0/7 weeks.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It was anticipated that approximately 
6900 mother-infant pairs would be needed to accumulate 124 per-protocol cases prior to the 
global COVID-19 pandemic.  With the variable RSV season, the sample size may need to be 
increased and enrollment could go up to 10,000 maternal participants based on the number of 
cases of RSV.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF for this study will be 
120 µg (60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.
Note: Maternal participants will include adolescent females who may be referred to as 
“minors.”  Information/assessments for minors may require parental/legal guardian 
awareness/approval per local regulations.
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term RTI 
surveillance and safety oversight to address safety and the possibility of conferred enhanced 
protection (antibody persistence) during a second RSV season. 
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All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. In addition, this study will use an 
E-DMC to monitor vaccine safety and efficacy and study futility.
4.1.1. Approximate Duration of Participation for Each Participant
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on GA at the time of vaccination and when the infant is 
actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth. 
4.1.2. Approximate Number of Participants
Healthy pregnant women will be randomly assigned to a study intervention. It was 
anticipated that approximately 6900 mother-infant pairs would be needed to accumulate 
124 per-protocol cases as defined in Section 9.2 of the protocol prior to the global COVID-19 
pandemic.  With the variable RSV season, the sample size may need to be increased and 
enrollment could go up to 10,000 maternal participants based on the number of cases of 
RSV.  Enrollment will be monitored to ensure that participants will be recruited from both 
the northern and southern hemispheres. Enrollment may vary depending on the incidence in 
the placebo group, the true underlying VE, the dropout rate, and a potential early stop for VE
or futility.
4.2. Scientific Rationale for Study Design
Refer to Section 2.1.
4.3. Justification for Dose
The final dose and formulation of RSVpreF selected for use in this study is based on the 
safety and immunogenicity data from the ongoing C3671003 maternal immunization study
(A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093) and the first-in-human (FIH) study C3671001.
The FIH study was designed to describe the safety, tolerability, and immunogenicity of 
6 RSVpreF candidates with bivalent formulations (RSV A and B) at 3 escalating dose levels 
of 60 µg (30 µg A and 30 µg B), 120 µg (60 µg A and 60 µg B), and 240 µg (120 µg A and 
120 µg B) of the RSV prefusion F antigen, with or without Al(OH)3, when administered 
alone or concomitantly with seasonal inactivated influenza vaccine.  The study utilizes a 
sentinel cohort (N=168; Phase 1) and an expanded cohort (N=1014; Phase 2).  Nonpregnant 
female and male study participants of 2 age groups, 18 through 49 years of age and 
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50 through 85 years of age, were enrolled into both cohorts.  The age groups are being run in 
parallel. 
An interim analysis of participants 18 through 49 years of age, including safety and 
tolerability (n=533) and immunogenicity (n=513) data up to 1 month after vaccination in the 
expanded cohort and additional immunogenicity data up to 3 months after vaccination in the 
sentinel cohort, has shown the RSVpreF candidate to be immunogenic and well tolerated. 
Local reactions and systemic events were noted to be predominantly mild or moderate across 
all doses and formulations, which is consistent with the current safety profile. The safety 
results from this planned interim analysis of healthy male and nonpregnant female 
participants 18 through 49 years of age are consistent with those from the sentinel-cohort 
analysis and indicate that RSVpreF has an acceptable safety profile and is well tolerated.
The immunogenicity results showed that RSVpreF elicited neutralizing titer geometric mean 
fold rises (GMFRs) of 10 to 20, 1 month after vaccination, depending on the formulation. 
Similarly, across all dose levels, with and without Al(OH)3, RSVpreF elicited high 
1-month-postvaccination RSV A and RSV B neutralizing GMTs. Overall, RSVpreF elicited 
anti–prefusion F immunoglobulin G1 (IgG1) responses that paralleled the elicited 
RSV-neutralizing responses. The ratio of RSV 50% neutralizing antibody titer GMFRs to 
prefusion RSV F binding IgG1 titer GMFRs (calculated with combined data for subgroups A 
and B) for the sentinel and expanded 18 through 49 years of age cohorts combined ranged 
from 0.62 to 0.76. The IgG1 and neutralization responses were similar in antigen-level dose
response, in equivalence of RSV A titer GMFRs to RSV B titer GMFRs, and in a lack of 
effect of Al(OH)3. 
Safety data for 403 mother/infant pairs, from maternal participants through 1 month after
maternal vaccination and for their infants from birth through the first month of life, in 
Study C3671003 provide further evidence of the safety of RSVpreF in maternal vaccine 
recipients, and initial evidence of the safety of maternal vaccination with RSVpreF for the 
infant. In maternal participants, solicited symptoms were generally mild to moderate in 
intensity and of short duration. Unsolicited AEs were consistent with anticipated events in 
this participant population and did not indicate any differences between RSVpreF and control 
recipients. No differences in pregnancy (eg, reports of preterm delivery or obstetric 
complications) and birth outcomes (eg, reports of respiratory distress at delivery or presence 
of congenital anomalies) were observed between RSVpreF and control recipients. No 
differences in the number or types of AEs reported were observed between infants born to 
mothers receiving RSVpreF and those receiving placebo in the first month of life.
The high ratio of RSV-neutralizing antibody titer GMFRs to prefusion F–binding titer 
GMFRs elicited by Pfizer’s RSVpreF candidate indicates that most of the elicited antibody 
can neutralize the virus. It is assumed that this reflects the ability of the antibodies to prevent 
RSV disease in immunized participants and, in the case of maternal immunization, prevent 
disease in their infants.
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The primary mechanism for protection of infants by the RSV maternal vaccine is 
neutralization of the virus by transplacentally transferred antibody, which is increased by 
immunization.  Maternal antibody decays exponentially in infants.  Therefore, it is 
anticipated that higher titers of transferred neutralizing antibodies will provide greater levels 
and durations of infant protection.  Results from the C3671001 FIH trial were used to 
determine the doses and formulations that are currently under investigation in the Phase 2b 
maternal immunization study: 120 µg or 240 µg of RSVpreF with or without Al(OH)3. 
These doses are expected to provide the greatest potential level of transplacental antibody 
transfer to infants and, therefore, the greatest potential benefit.  The dose and formulation of 
RSVpreF for the Phase 3 study was determined by the evaluation of the 1-month safety, 
tolerability, and immunogenicity results from the C3671003 maternal Phase 2b trial,
including infant RSV-neutralizing titers at birth.
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last visit.
The end of the study is defined as the date of the last visit of the last infant participant in the 
study. The study may also be terminated earlier for efficacy or futility as described in
Section 9.5.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
5.1.1. Inclusion Criteria – Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply 
(refer to the investigator site file [ISF] for further eligibility details regarding region-specific 
timing of vaccination with respect to RSV seasonality and maternal gestational age at 
vaccination):
Note: In countries/locales where study procedures used to determine eligibility criteria 
(eg, ultrasound examination, human immunodeficiency virus [HIV] testing, syphilis testing) 
are not performed as part of routine prenatal care, they must be performed as part of this 
clinical trial and reviewed by the investigator or qualified designee within 28 days prior to 
randomization.  Maternal participants must provide informed consent prior to 
performing any procedures, including those that are being done exclusively to meet 
study eligibility criteria.
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Note: Country-specific modifications associated with the study eligibility criteria are 
documented in Appendix 7, Appendix 8, and Appendix 9.
Age and Sex:
1. Healthy women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation 
on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are 
at no known increased risk for complications. 
Note: GA must be based upon 1 of the following composite criteria based on timing and 
availability of data on the last menstrual period (LMP) and an ultrasound examination 
performed in the first or second trimester.35  The earliest ultrasound data available during 
the current pregnancy should be used. In countries where the routine practice is for the 
GA determination to be based upon the first trimester ultrasound examination alone, 
without the LMP, this routine practice will be accepted.
a.
First-trimester data available (data obtained at ≤13 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a first-trimester ultrasound examination.

If there is a discrepancy of >5 days between the LMP-determined GA and an 
ultrasound result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA 
should be determined using the first-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and an 
ultrasound result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, 
then the GA should be determined using the first-trimester ultrasound result.
b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a second-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and the 
ultrasound result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >10 days between the LMP-determined GA and the 
ultrasound result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >14 days between the LMP-determined GA and the 
ultrasound result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
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Type of Participant and Disease Characteristics:
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Receiving prenatal standard of care based on country requirements.
4. Had a fetal anomaly ultrasound examination performed at ≥18 weeks of pregnancy with 
no significant fetal abnormalities observed. 
5. Determined by medical history, physical examination, and clinical judgment to be 
appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) 
surface antigen test during this pregnancy and prior to randomization (Visit 1). 
7. Intention to deliver at a hospital or birthing facility where study procedures can be 
obtained. 
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol OR
If the maternal participant is illiterate, a thumbprinted informed consent must be 
obtained, which must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process confirming that the maternal participant 
has been informed of all pertinent aspects of the study.
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5.1.2. Inclusion Criteria – Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a 
thumbprinted informed consent must have been obtained, which must have been signed 
and dated by an impartial witness who was present throughout the entire informed 
consent process confirming that the maternal participant/parent(s)/legal guardian(s) has 
been informed of all pertinent aspects of the study for herself (maternal participant) and 
her fetus/infant prior to taking part in the study.
Note: Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements. 
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
5.2. Exclusion Criteria 
5.2.1. Exclusion Criteria – Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not 
available, the BMI at the time of the first obstetric visit during the current pregnancy may 
be used.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any related 
vaccine.
4. Current pregnancy resulting from in vitro fertilization.  Participants known to have used 
clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are 
permitted.
5. Current pregnancy complications or abnormalities at the time of consent that will 
increase the risk associated with the participation in and completion of the study, 
including but not limited to the following:

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.
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
Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated 
hypothyroidism.  This also includes disorders of glucose intolerance (eg, diabetes 
mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if 
uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the 
investigator’s judgment, that will increase the risk associated with the participation in and 
completion of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks’ gestation.

Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or significant congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the maternal 
or infant participant’s participation in, and completion of, the study or could preclude the 
evaluation of the maternal participant’s response (includes positive serologic testing for 
regional endemic conditions assessed during routine maternal care, as per local standards 
of care and obstetric recommendations).
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment.
9. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to 
consent and/or during study participation.
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11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of 
systemic corticosteroids for >14 days within 28 days prior to study enrollment.  
Prednisone use of <20 mg/day for ≤14 days is permitted. Inhaled/nebulized, 
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
12. Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an 
exclusion criterion for the study when elicited in participant screening, though it may be 
considered illicit in some locales.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before 
investigational product administration, or planned receipt through delivery, with 
1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt 
during study participation. Note: Licensed COVID-19 vaccines or COVID-19 vaccines 
authorized for temporary or emergency use will not be prohibited during the course of 
this study.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
5.2.2. Exclusion Criteria – Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and if no other exclusion criteria are met.  
The prevaccination blood draw and vaccination should take place on the same day. In the 
event that this is not possible, the prevaccination blood draw is also permissible within 7 days 
before the vaccination visit.

Current febrile illness (body temperature ≥38°C [≥100.4°F]) or other acute illness within 
48 hours before investigational product administration.

Diagnosed malaria within the last 7 days prior to investigational product administration.
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
Receipt of any inactivated vaccine (including licensed COVID-19 vaccines or COVID-19 
vaccines authorized for temporary or emergency use) within 14 days or any live vaccine 
within 28 days before investigational product administration.

If systemic corticosteroids (equivalent of ≥20 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical 
study but are not subsequently randomly assigned to investigational product. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs.
Maternal participants who do not meet the criteria for participation in this study (screen 
failure) may be rescreened. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
For this study, the investigational product(s) are RSVpreF and placebo (lyophile match).
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine 
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.  The
RSV drug product will be 120 µg of the RSV prefusion F antigen.  The drug product is 
supplied as a lyophilized white cake in a 2-mL glass vial, with a 13-mm lyophilization 
stopper, aluminum overseal, and flip-off cap. The drug product will be reconstituted by a 
diluent consisting of sterile water in a prefilled syringe (PFS). The lyophilized drug product 
contains excipients that, after reconstitution, will yield a solution as detailed in the IB.
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The fill volume of the drug product vial and diluent PFS are designed such that the intended 
vaccine dose is delivered by injecting the entire contents of the syringe.
6.1.2. Placebo
Placebo will be a lyophile match to the vaccine, which will consist of excipients matched to 
those used in the RSVpreF vaccine formulation, minus the active ingredients. 
The physical appearance of the reconstituted RSVpreF and placebo will be matched, and the 
study will be conducted in a double-blinded manner.
The fill volume of the placebo vial and diluent PFS is designed such that the intended 
placebo dose is delivered by injecting the entire contents of the syringe.
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
6.1.3. Administration
Maternal participants will receive 1 dose of investigational product at the vaccination visit 
(Day 1) in accordance with the study’s SoA.  The investigational product will be 
administered intramuscularly by injecting the entire contents of the syringe into the deltoid 
muscle, preferably of the nondominant arm, unless medically contraindicated, in which case 
the injection may be administered in the dominant arm. Investigational product
administration will be performed by appropriately designated study staff at the investigator 
site.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance. 
Investigational product administration details will be recorded on the case report form (CRF).
6.1.4. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluent for the 
investigational product (RSV vaccine or placebo). The investigational product supplies are 
provided in a kit that contains the investigational product (RSV vaccine or placebo 
lyophilized powder in a vial), a prefilled syringe containing sterile water, and a vial adapter.
Instructions for medical device use are provided in the investigational product manual 
(IP manual).
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Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the study personnel throughout the study.
Please refer to Section 8.3.9 for details. 
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention, as applicable for 
temperature-monitored shipments. 
2. Only maternal participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking days must indicate the minimum and maximum 
temperature since previously documented for all site storage locations upon return to 
business.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  All study interventions will be 
accounted for using an investigational product accountability form/record.
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
6. Study interventions should be stored in their original containers and in accordance with 
the labels.
7. See the IP manual for storage conditions of the study intervention once reconstituted.
8. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use of 
the study intervention after the temperature excursion. Use of the study intervention prior 
to Pfizer approval will be considered a protocol deviation. Specific details regarding the 
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definition of an excursion and information the site should report for each excursion will 
be provided to the site in the IP manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
6.2.1. Preparation and Dispensing
Refer to the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
Investigational product and placebo will be prepared by qualified site personnel according to 
the IP manual.  The investigational product will be administered only to maternal participants 
who are blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Blinding of Study Site Personnel 
This study is a double-blinded study, as the physical appearance of RSVpreF and placebo 
will be matched. The maternal participant, her parent(s)/legal guardian (if a minor), 
investigator, study coordinator, and all site staff will be blinded.
Please refer to the IP manual for further details.
6.3.2. Blinding of the Sponsor
The sponsor study team members will be blinded throughout the study to the vaccine 
assignments of all participants enrolled in the study. 
Laboratory personnel performing the serology and virology assays will remain blinded to 
vaccine assigned/received throughout the study.
6.3.3. Allocation to Investigational Product
Allocation (randomization) of maternal participants to vaccine groups will proceed through 
the use of an interactive response technology (IRT) system (interactive Web-based response 
[IWR]).  The site personnel (study coordinator or specified designee) will be required to 
enter or select information including but not limited to the user’s identification (ID) and 
password, the protocol number, and the maternal participant number.  The site personnel will 
then be provided with a vaccine assignment, randomization number, and dispensable unit 
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(DU) or container number as investigational product is being supplied via the IRT system.  
The IRT system will provide a confirmation report containing the maternal participant 
number, randomization number, and DU or container number assigned. The confirmation 
report must be stored in the site’s files. 
Note: Maternal participants will be randomized to a vaccine group as described above.  The 
infants of the maternal participants will be manually assigned an infant participant number at 
birth.
Investigational product will be dispensed and administered at study Visit 1 summarized in 
the SoA. 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Maternal participants will be assigned to receive investigational product according to the 
randomization scheme.  Investigators will remain blinded to the investigational product 
assigned to each maternal participant throughout the course of the study.
6.3.4. Breaking the Blind 
The study will be maternal participant and investigator blinded.
At the initiation of the study, the investigator will be instructed on the method for breaking
the blind for an individual participant.  The method will be an electronic process.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the participant.  The 
investigators should make every attempt to contact a member of the sponsor’s study team 
prior to breaking the blind.  When the blinding code is broken, the reason must be fully
documented and entered on the CRF.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy 
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal Participants

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study. Note: COVID-19 vaccines authorized for temporary or emergency use will not be 
prohibited during the course of this study.
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
Receipt of blood/plasma products or Ig, from 60 days before investigational product 
administration, or planned receipt through delivery, with 1 exception, Rho(D) immune 
globulin (eg, RhoGAM), which can be given at any time.

Immunosuppressive therapy is prohibited during the course of the study.

Nonstudy vaccines may not be given concomitantly with the investigational product or 
within 7 days after investigational product administration (Day 1 to Day 7), except if 
medically necessary (eg, during an outbreak or pandemic situation).

Note: Licensed vaccines containing pertussis (including Tdap) may not be 
coadministered with the investigational product or given within 14 days after 
investigational product administration (Day 1 to Day 14), except if medically necessary 
(eg, during an outbreak- or pandemic-related situation).
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal Participants

Licensed vaccines (including influenza vaccine, tetanus toxoid, tetanus diphtheria 
vaccines, licensed COVID-19 vaccines, and COVID-19 vaccines authorized for 
temporary or emergency use) may be given during the study starting 7 days after
investigational product administration (Day 8), with the exception of licensed vaccines 
containing pertussis (including Tdap), which may be given starting 14 days after 
investigational product administration (Day 15) as detailed in Section 6.5.1.

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. Short-term systemic corticosteroid (equivalent of <20 mg/day of prednisone)
use for ≤14 days prior to the administration of investigational product is permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during participant participation in the 
study.
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following vaccinations and treatments for maternal participants would require reporting 
in the CRF during the study: 

Details of any vaccinations given at any time during the pregnancy through the final 
study visit will be collected and recorded in the CRF.

Details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given to the maternal participant at any time during the 
pregnancy or during the study will be collected and recorded in the CRF.
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
Any prescribed medications taken to treat medically attended respiratory illnesses from 
enrollment until the final study visit will be recorded in the CRF.
Concomitant medications not meeting the criteria above will be assessed but not documented 
on the CRF.
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant Participants

Investigational vaccines, drugs, nutritional products, or medical devices are prohibited 
during the course of the study.
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant Participants

ONLY routine treatments, routine vaccinations, and routine procedures 
(eg, circumcision) are permitted at any time during the study, in accordance with national 
recommendations, medical standard of care, or accepted practice.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during infant participant participation in the study.

Local anesthetic may be applied to the site of the blood draw, as appropriate.
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications – Infant 
Participants
The following CRF reporting guidelines are applicable to treatments given to infant 
participants during the study:

Details of any Ig (including monoclonal antibodies [eg, Synagis] or immune globulin 
[eg, hepatitis B immune globulin (HBIG)]) or blood products (eg, whole blood, packed 
cells) given to the infant participant will be collected from the time of birth until the final 
study visit and recorded in the CRF.

Any prescribed medication taken to treat medically attended respiratory illnesses from 
the time of birth until the final visit.

Details of IV fluids given during an MA-RTI will be collected and recorded in the CRF.
6.6. Dose Modification
Dose modification is not applicable in this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Discontinuation of study intervention is not applicable in this study.
7.2. Participant Discontinuation/Withdrawal From the Study
A maternal participant may withdraw from the study at any time at her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. An infant participant may withdraw from the study at 
any time at the request of his or her parent(s) and/or legal guardian(s) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.
The participants, or, if appropriate, their parent(s) and/or legal guardian(s), should be
questioned regarding their reason for withdrawal. The participant will be permanently
discontinued from the study at that time.
If a maternal participant withdraws from the study, she may request destruction of any 
remaining samples taken and not tested, but data already generated from the samples will 
continue to be available and may be used to protect the integrity of existing analyses. If an 
infant participant is withdrawn from the study, his or her parent(s) and/or legal guardian(s) 
may request destruction of any remaining samples, but data already generated from the 
samples will continue to be available, and may be used to protect the integrity of existing 
analyses. The investigator must document any such requests in the site study records and 
notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
Participants who withdraw after randomization will not be replaced.
7.3. Withdrawal of Consent
Maternal participants and parent(s)/legal guardian(s) of infant participants born to maternal 
participants who request to withdraw consent from any further study contact or with persons 
previously authorized by the participant to provide this information should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible.  The withdrawal of consent should be explained in detail in the medical records by 
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the investigator, as to whether the withdrawal is only from study procedures and/or 
postvaccination study follow-up. If the participant (maternal or infant) only withdraws from 
a study procedure, safety information should be completed until the end of the study, unless 
consent for further contact has been withdrawn.  In the event that vital status (whether the 
participant is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
The regulatory and ethical considerations for this study, including the informed consent 
process, are summarized in Section 10.1.1 and Section 10.1.3.
7.4. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant, or parent(s) and/or legal guardian(s), and 
reschedule the missed visit as soon as possible and counsel the participant or parent(s) 
and/or legal guardian(s) on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or parent(s) and/or legal guardian(s) wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record.

Should the participant or parent(s) and/or legal guardian(s) continue to be 
unreachable, the participant will be considered to have withdrawn from the study.
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
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Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the maternal participant’s routine clinical 
management and obtained before signing of the ICD may be utilized for baseline 
purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA and protocol.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
8.1. Efficacy Assessments
8.1.1. Efficacy Assessments – Infant Participants
MA-RTIs in the infant participant will be identified from 72 hours after the infant’s delivery 
until the end of the infant’s participation in the study.  If the infant participant meets any RTI 
criteria listed below that require a visit by or a visit to an HCP (outpatient or inpatient visit, 
emergency room, urgent care, or scheduled home visit), an RTI study visit by the study staff 
will be required (see Section 8.11.7).
The RTI criteria are if the infant experiences 1 or more of the following respiratory signs or 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any duration

Cough

Inability to feed for any duration due to respiratory symptoms
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
Apnea

Any other respiratory symptom of concern 
Evaluation of these MA-RTI events will be based on predefined clinical signs and symptoms 
and testing criteria (shown in Table 1) obtained at the medically attended visit with the 
healthcare provider and/or the study visit. These events will be assessed and confirmed to be 
contributing to the study endpoints by an independent EAC as per the protocol.
8.1.1.1. Midturbinate Nasal Swab Collection and Testing Requirements for Endpoint 
Confirmation – Infant Participants
Midturbinate nasal swabs will be collected for RSV analyses from infant participants at each 
RTI study visit during the RSV surveillance period from birth until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). The swabs
will be sent to Pfizer for centralized reverse transcription–polymerase chain reaction 
(RT-PCR) testing.
RSV testing performed locally as part of routine care will be considered valid when analyzed 
under the following conditions:  

Nucleic acid amplification technology (NAAT)-based test result positive for RSV was 
obtained using a Food and Drug Administration (FDA)-cleared assay.
AND

NAAT-based test result was obtained in a laboratory that is currently Clinical Laboratory 
Improvement Amendments (CLIA)-certified or has the equivalent US 
certification/accreditation (eg, College of American Pathologists [CAP]) or the equivalent 
ex-US certification as outlined in the adjudication charter. 
Note: Rapid antigen-based test results will not be considered for endpoint assessment.
Study samples should be collected as close to the medical visit as possible and preferably 
within 72 hours of the MA-RTI visit. Study samples positive for RSV by RT-PCR as 
defined above will count toward the endpoint definition when collected for up to 10 days 
after the MA-RTI, where Day 1 is the day of the MA-RTI visit. These results will be used 
for MA-RTI endpoint definition and confirmation as detailed in Table 1.
8.1.1.2. Events for Adjudication and Submission Guidance – Infant Participants
To maintain scientific integrity, this protocol will use an EAC for the adjudication of all 
efficacy endpoints as summarized below.  The EAC will remain blinded to the maternal 
participants’ vaccine assignments, and the EAC’s assessment of these events will represent 
the final confirmed endpoint classification of the event. 
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The efficacy-related events for adjudication include all MA-RTI events. The study 
definitions for endpoint events and the MA-RTI adjudication criteria for the EAC, including 
roles and responsibilities, are specified in the endpoint adjudication committee charter 
(EACC). 
The identification of an MA-RTI will be made by the investigational site and communicated 
to Pfizer or its designee. However, these MA-RTI events may also be identified by Pfizer or 
its designee during the review of clinical data listings or by site monitors during routine 
monitoring of the infant participants’ study records. Pfizer or its designee will notify the 
investigational site of any events identified during this process.
The EAC is responsible for adjudicating whether MA-RTI events fulfill the protocol-defined 
clinical criteria as a primary endpoint, whether the event was due to RSV based on 
confirmatory testing, and the severity of the illness (eg, MA-RTI, MA-LRTI, or severe 
MA-LRTI).  The EAC will adjudicate all RSV-positive MA-RTI cases through the active 
follow-up period including all cases occurring up to 180 days after birth. The EAC will 
adjudicate severe manifestations of RSV: all RSV-associated cases of hospitalization and 
severe MA-LRTI. All deaths during the study are to be reported to Pfizer Safety upon 
awareness. 
The Pfizer study team or designee will provide a listing of specific documents needed to 
support endpoint adjudication by the EAC. These documents will be detailed in the EACC
and the ISF.  Obtaining and submitting the documentation, including results of local testing 
for RSV, will be the responsibility of the investigational site. Documentation will vary based 
on the potential endpoint requiring adjudication and may include (but not be limited to) 
emergency room visit records, hospital discharge summaries, clinic and/or progress notes, 
diagnostic tests, pathology reports, autopsy reports, and death certificate information, as 
applicable.
Pfizer may request that additional cases of interest be reported to the committee in addition to 
those listed above, including cases in which RSV testing is indeterminant or otherwise 
unclear. Cases that are determined to be RSV positive using non–NAAT-based clinical 
testing can be adjudicated, explored, and summarized descriptively.
8.1.2. Exploratory Efficacy Assessments – Maternal Participants
An MA-RTI will be identified from vaccination until the end of the study and will contribute 
to an exploratory endpoint for maternal participants.  The definition and assessment criteria 
as described in Section 8.10.6 include a visit by or to a healthcare provider (outpatient or 
inpatient visit, emergency room, urgent care, or home visit) for any symptoms in the RTI 
criteria as detailed in Table 2.
The maternal participant or her parent(s)/legal guardian (if a minor) should contact the study 
staff immediately but no later than the next scheduled visit to report RTI signs and symptoms 
for which she sought medical attention. The procedures as detailed in Section 1.2.3.1 and 
Section 8.10.6 will be required to capture the event in the CRF.
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8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal and Infant 
Participants
Infant MA-RTI events that are consistent with the clinical and endpoint definitions for infant 
participants should not be recorded as AEs. These data will be captured as efficacy 
assessment data only, as these are expected endpoints.
For maternal participants, MA-RTI events that are consistent with the clinical and endpoint 
definition will be captured as detailed in Section 8.1.2 and will not be recorded as AEs.
Any event that the investigator has judged to have a causal relationship with the 
investigational product or to have resulted in death MUST be reported to Pfizer Safety as 
described in Appendix 2, even if that event is a component of an endpoint.
8.1.4. Immunogenicity Assessments
8.1.4.1. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be approximately 30 mL (~15 mL/visit).
8.1.4.2. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical 
Consideration for Clinical Trials Performed in Children.36
All infants will have a cord blood sample collected at birth. The cord blood is collected from 
the umbilical cord vein attached to the placenta after the umbilical cord has been clamped 
and cut. Blood should be collected as soon as feasible after birth to minimize coagulation 
and maximize volume. The total volume of cord blood to be collected for antibody 
assessment in this study will be 10 mL. 
If cord blood is unavailable, a blood sample may be collected from the infant participant up 
to 7 days after birth but preferably within 24 hours after birth.  The infant’s weight must 
be used to determine the volume of blood that can be collected (see Table 3).
A blood sample will be collected from the infant participant only if a cord sample is not
obtained. In the event that a sample is collected, the volume of blood will vary depending on 
the infant’s weight.
The maximum volume of blood collected from the infant in the absence of cord blood will be 
no more than 5 mL.
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Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained
Body Weight (in kg)
Approximate Volume of Blood (in mL) 
to Be Collected 
<1.3
No blood draw
1.3 to ≤2.4
1.0
>2.4 to ≤3.7
2.0
>3.7 to ≤4.9
3.0
>4.9 to ≤6.2
4.0
>6.2
5.0
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant Participants
Maternal sera (prevaccination/time of delivery) and infant cord blood collected will be 
assayed for RSV A and RSV B serum neutralizing titers and anti-RSV prefusion F IgG 
levels. Maternal sera collected may be tested for Ig levels against nonvaccine RSV antigens
to assess natural RSV exposure.
RSV A and RSV B serum neutralizing titers will be determined and reported as the 
neutralizing titer. IgG levels will be determined against both RSV A and RSV B prefusion F 
antigens in a direct-binding Luminex immunoassay (dLIA) and reported as an anti–
prefusion F IgG level.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development – Maternal and Infant Participants
Samples remaining after completion of the planned assays from blood draws or infant 
respiratory nasal swab specimens taken throughout the study may be used for additional 
vaccine and infectious disease related research. Samples may also be used for assay 
development, standardization, qualification, and validation.  This work is critical in the 
development, qualification, and validation of serological assays and is required by regulatory 
authorities for their use in the licensure of a vaccine.
8.1.4.5. Respiratory Pathogens – Infant Participants
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI
visit during the RSV surveillance period from birth until Visit 3, and for all hospitalizations 
due to an RTI and severe cases of MA-LRTI during the RTI surveillance period from 
Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1).
Samples will be analyzed for RSV A, RSV B, and other respiratory pathogens by polymerase 
chain reaction (PCR)-based assays at a central laboratory. Additional exploratory analyses 
may also be performed.
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Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.6. Biological Samples – Maternal and Infant Participants
Samples will be used only for scientific research.  Each sample will be labeled with a code so 
that the laboratory personnel testing the samples will not know the maternal or infant
participant’s identity.  Samples that remain after performing assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.  If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No sequencing of the maternal or infant participant’s DNA will be performed. 
The maternal participant may request that her (or her infant’s) samples, if still identifiable, be 
destroyed at any time; however, any data already collected from those samples will still be 
used for this research.  The biological samples may be shared with other researchers as long 
as confidentiality is maintained, and no testing of the maternal and infant participant’s DNA 
is performed.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
Safety parameters will be assessed as described in the SoA and below for both maternal and 
infant participants.
8.2.1. Participant Electronic Diary – Maternal Participants
All maternal participants vaccinated in the study will be observed for at least 30 minutes after 
investigational product administration for any acute reactions. For all maternal participants, 
prespecified local reactions and systemic events will be collected for 7 days after vaccination.
Maternal participants will be required to use an electronic diary (e-diary), installed on a 
provisioned device or as an application on a personal device, and will be asked to monitor 
and record local reactions, systemic events, and temperature each evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  Prior 
to vaccination, a baseline assessment of prespecified systemic events will be recorded in the 
e-diary.
The e-diary allows recording of these assessments only within a fixed time window each day, 
thus providing the accurate representation of the maternal participant’s experience at that 
time.
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If the maternal participant is illiterate, a study staff/field worker may visit the maternal 
participant in her home or contact her via phone daily after vaccination to assess and record 
local reactions, systemic events, and temperature each day (beginning in the morning) for 
6 days following vaccination (Day 2 through Day 7). Maternal participants or her 
parent(s)/legal guardian (if a minor) may call the site and report additional local reactions and 
systemic events at any time during the Day 1 to Day 7 reporting period.  The study staff/field 
worker will be required to record these data on a provisioned device or an application on a 
personal device, thus providing the accurate representation of the maternal participant’s 
experience at that time.  For events persisting at Day 7 and use of antipyretic medication 
continuing at Day 7, the field worker will continue to visit the participant and record 
information until resolution.
Data on local reactions, systemic events, and temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via an internet-based 
portal.  At intervals agreed to by the vendor and Pfizer, these data will be transferred 
electronically to Pfizer for analysis and reporting.  These data do not need to be recorded by 
the investigator in the CRF, except the following conditions:

If a maternal participant withdraws because of prompted events recorded in the e-diary, 
the event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF. 
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate maternal participant compliance and as part of the 
ongoing safety review. These prospectively collected occurrences of local reactions and 
systemic events are graded as described in Section 8.2.1.1 and Section 8.2.1.2.
8.2.1.1. Local Reactions – Maternal Participants
Following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), the 
maternal participants or her parent(s)/legal guardian (if a minor)/study staff member/field 
worker will be asked to assess redness, swelling, and pain at the injection site and to record 
the symptoms in the e-diary or appropriate device, in the evening or daily based on local 
practice.
Redness and swelling will be measured by the maternal participant/study staff/field worker 
and recorded in measuring device units (range: 1 to 20 and 21+) and then categorized during 
analysis as mild, moderate, or severe based on the grading scale in Table 4. Measuring 
device units can be converted to centimeters according to the following scale: 1 measuring 
device unit = 0.5 cm.
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A maternal participant with severe redness, swelling, or pain at the injection site will be 
prompted to contact the investigator to perform an unscheduled visit to assess the reaction or 
will be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate.  In the event that the maternal participant
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor).
Only an investigator or a qualified designee is able to classify a maternal participant’s local 
reaction as Grade 4, after clinical evaluation of the maternal participant or documentation 
from another medically qualified source (eg, emergency room or hospital record) or, in the 
case of pain at the injection site only, contact with the maternal participant.  If a maternal 
participant experiences a Grade 4 local reaction, the investigator must immediately notify the 
sponsor.  A Grade 4 reaction will be collected as an AE on the CRF.  The event will be 
graded using the AE intensity grading scale (Section 10.2.4).
The site staff/field worker will educate the maternal participant and her parent(s)/legal 
guardian (if a minor) regarding signs and symptoms that would prompt site contact.
If a local reaction persists beyond the end of the e-diary period, the maternal participant or 
her parent(s)/legal guardian (if a minor) will be requested to report that information and/or 
any new AEs that develop to the investigator, or the study staff/field worker will continue to 
call or visit the maternal participant to assess and record the information until resolution, as 
per local practice. The investigator will enter this additional information in the maternal 
participant’s source notes and CRF.
Table 4.
Grading Scale for Local Reactions
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis
Pain (at the 
injection site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a maternal participant’s local reaction as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
contact with the maternal participant or her parent(s)/legal guardian (if a minor).  Grade 4 local reactions 
will be collected on the AE case report form and assessed by the investigator using the AE intensity 
grading scale as detailed in Section 10.2.4.
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8.2.1.2. Systemic Events – Maternal Participants
Prior to vaccination on Day 1, a baseline assessment of fatigue, headache, vomiting, 
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e-diary. Following 
vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), maternal 
participants or their parent(s)/legal guardian (if a minor) will be asked to assess fatigue, 
headache, vomiting, nausea, diarrhea, muscle pain, and joint pain and to record the symptoms 
in the e-diary in the evening or, based on local practice in certain countries/locales, a study 
staff member/field worker will call or visit maternal participants daily after vaccination to 
assess the presence of systemic events each day (beginning in the morning) for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  The 
study staff member/field worker will record the symptoms in the e-diary daily. The 
symptoms will be assessed by the maternal participant according to the grading scale in 
Table 5.  Maternal participants and their parent(s)/legal guardian (if a minor) will also be 
instructed to contact site staff if they visit the emergency room or are hospitalized for severe 
fatigue, headache, vomiting, nausea, diarrhea, muscle pain, or joint pain within 7 days after 
vaccination. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor). The study staff/field worker may also contact the 
maternal participant or her parent(s)/legal guardian (if a minor) to obtain additional 
information on events entered into the e-diary.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic 
event as Grade 4, after clinical evaluation of the maternal participant or documentation from 
another medically qualified source (eg, emergency room or hospital record) or contact with 
the maternal participant.  If a maternal participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.  Grade 4 reactions will be collected as an 
AE on the CRF.  The event will be graded using the AE intensity grading scale 
(Section 10.2.4).
Further, if a systemic event persists beyond the end of the e-diary period, the maternal 
participant or her parent(s)/legal guardian (if a minor) will be requested to report that 
information and/or any new AEs that develop to the investigator, or the study staff/field 
worker will continue to call or visit the maternal participant to assess and record the 
information until resolution, as per local practice. The investigator will enter this additional 
information in the maternal participant’s source notes and CRF.
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Table 5.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness in 
diaries)
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Headache
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Vomiting
1 to 2 times in 24 hours
>2 times 
in 24 hours
Requires 
intravenous 
hydration
Emergency room 
visit 
or hospitalization 
for severe vomiting
Nausea
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe nausea
Diarrhea
2 to 3 loose stools
in 24 hours
4 to 5 loose stools
in 24 hours
6 or more loose 
stools
in 24 hours
Emergency room 
visit
or hospitalization 
for severe diarrhea
Muscle pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe muscle pain
Joint pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe joint pain
a.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic event as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the maternal participant or her 
parent(s)/legal guardian (if a minor).  Grade 4 systemic reactions will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.1.3. Temperature – Maternal Participants
A digital thermometer will be given to the maternal participant with instructions on how to 
measure oral temperature at home in degrees Celsius.  Temperature will be collected in the 
evening for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination) and at any time during the 7 days following vaccination that fever is suspected. 
Similarly, based on local practice in certain countries/locales, the study staff/field worker will 
call or visit maternal participants daily for 6 days after vaccination (Day 2 through Day 7, 
where Day 1 is the day of vaccination) to collect the temperature.
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Fever is defined as an oral temperature of ≥38.0°C (≥100.4°F). The highest temperature for 
each day will be recorded in the e-diary, where possible. In certain countries/locales, if a 
temperature of ≥38.0°C (≥100.4°F) is recorded for a maternal participant during the 
collection of diary events after vaccination, the study staff/field worker will perform a rapid 
test for malaria as per local practice.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature less than 38.0°C [100.4°F]) in order to 
collect a stop date in the CRF. 
A maternal participant with a fever >38.9°C (>102.0°F) will be prompted to contact the 
investigator. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as applicable. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor).  The investigator or qualified designee will assess 
the fever and perform an unscheduled visit as appropriate.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as 
Grade 4, after clinical evaluation of the maternal participant, documentation from another 
medically qualified source (eg, emergency room or hospital record), or contact with the 
maternal participant or her parent(s)/legal guardian (if a minor).  Grade 4 fevers will be 
collected on the AE CRF and assessed by the investigator using the AE intensity grading 
scale as detailed in Section 10.2.4.
Temperature will be measured and recorded to 1 decimal place and then categorized during 
analysis as mild, moderate, or severe based on the intensity grading scale provided in
Table 6.
Table 6.
Ranges for Fever
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fever
≥38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°C
a.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as Grade 4, 
after clinical evaluation of the maternal participant, documentation from another medically qualified 
source (eg, emergency room or hospital record), or contact with the maternal participant or her 
parent(s)/legal guardian (if a minor).  Grade 4 fevers will be collected on the AE case report form and 
assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant Participants
There are no protocol-required laboratory assessments.
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8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 4.  Device deficiencies are covered in Section 8.3.9.
AEs will be reported by the maternal participant/parent(s)/legal guardian(s).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7).
Each maternal participant or her parent(s)/legal guardian (if a minor) and parent/legal 
guardian/legally authorized representative of an infant participant will be questioned about 
the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
Maternal Participants
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each maternal participant including her fetus begins from the time the maternal 
participant and her parent(s)/legal guardian (if a minor) provides informed consent, which is 
obtained before participation in the study (ie, before undergoing any study-related procedure 
and/or receiving investigational product), through and including a minimum of 28 calendar 
days after the last administration of the investigational product.
In this study, the investigator and site staff will ensure the active elicitation and collection of 
safety events as detailed below:

The active collection period for nonserious AEs begins once informed consent has been 
provided and continues through a minimum of 28 calendar days after vaccination.

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

In addition, AEs occurring up to 48 hours after blood draws that are related to study 
procedures must be reported in the CRF.
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
Details of any MA-RTI will not be collected as AEs/SAEs from informed consent until 
the maternal participant completes the study, unless the investigator or an appropriate 
designee deems the event to be possibly related to the investigational product or to have
resulted in death as detailed in Section 8.1.2 and Section 8.1.3.
For maternal participants who are screen failures, the active collection period ends when 
screen failure status is determined.
Infant Participants
For the infant participant, the time period for actively eliciting and collecting safety events is 
detailed below:

The active collection period for nonserious AEs begins at birth and continues through and 
including a minimum of 28 calendar days after birth.

The active collection period for NDCMCs and SAEs begins at birth and continues 
through the last study visit.
o
Details of any MA-RTI will not be collected as AEs/SAEs from 72 hours after 
birth until the infant participant completes the study, unless the investigator or an 
appropriate designee deems the event to be possibly related to the investigational 
product or if the event resulted in death. See Section 8.1 for the reporting 
procedures for efficacy-related endpoints. Note: Details of the MA-RTI visit 
should be recorded in the eCRF.

In addition, AEs occurring up to 48 hours after blood draws or nasal swabs that are 
related to study procedures must be reported in the CRF.
For Both Maternal and Infant Participants
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For maternal participants, and parent(s)/legal guardian(s) of infant participants born to 
maternal participants, who withdraw from the study and withdraw consent for the collection 
of future information, the active collection period ends when consent is withdrawn. 
If a participant definitively discontinues or temporarily discontinues study intervention
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form.
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Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the Vaccine SAE Reporting Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the Vaccine SAE Reporting Form, immediately upon awareness and under no 
circumstances should this exceed 24 hours.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy; 
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those that occur within 1 month after birth; or congenital 
anomaly* [in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal 
death]), the investigator should follow the procedures for reporting SAEs.  In addition, infant 
deaths after 1 month of age should be reported as SAEs.
Further follow-up may be requested by the sponsor and will be handled on a case-by-case 
basis (eg, follow-up on preterm infants to identify developmental delays).
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety. 
The same is applied for those SAEs after the active collection period has ended, should they 
occur to the fetus.  In addition, infant deaths that occur after 12 months of age should be 
reported as SAEs when the investigator believes the SAE or death has at least a reasonable 
possibility of being related to investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.37
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All AEs/SAEs occurring in a participant during the active collection period, which begins 
after obtaining informed consent as described in Section 8.3.1, will be recorded on the AE 
section of the CRF.
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The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant or her parent(s)/legal guardian (if a minor) and
parent(s)/legal guardian(s) of infant participants born to maternal participants.
The investigator obtains general information on the pregnancy and its outcome for all study 
participants.  The investigator will follow the pregnancy until completion (or until pregnancy 
termination).  In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth.  In the event of a termination, the reason(s) for termination should be 
specified and, if clinically possible, the structural integrity of the terminated fetus should be 
assessed by gross visual inspection (unless preprocedure test findings are conclusive for a 
congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, stillbirth, neonatal death,
defined as those deaths that occur within 1 month after birth; or congenital anomaly* [in a 
live-born baby, a stillbirth, or a neonatal death]), the investigator should record this 
information in the CRF.  In addition, infant deaths after 1 month of age should be recorded in 
the CRF as SAEs. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.37
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.4).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 2.
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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
Potential efficacy endpoints on this study as defined in Section 8.1 will be excluded from the 
standard SAE reporting process unless deemed possibly related to investigational product.
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the 
Investigational Product
8.3.5.1. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Scenarios of exposure during breastfeeding for infants not delivered during the study must be 
reported, irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours 
of the investigator’s awareness, using the Vaccine SAE Reporting Form.  An 
exposure-during-breastfeeding report is not created when a Pfizer drug specifically approved 
for use in breastfeeding women (eg, vitamins) is administered in accord with authorized use.  
However, if the infant experiences an SAE associated with such a drug’s administration, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.2. Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
investigational product, which may or may not lead to the occurrence of an AE. Such 
persons may include HCPs, family members, and other roles that are involved in the trial 
participant’s care.
Note: This does NOT apply to maternal participants enrolled in this trial.
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In addition, the scenarios below describe environmental exposures that could lead to an 
exposure during pregnancy (EDP): 

A female becomes or is found to be pregnant, having been exposed (eg, because of 
environmental exposure) to the investigational product; or the female becomes or is 
found to be pregnant after being exposed to the investigational product;

A male has been exposed (eg, because of environmental exposure) to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy. 
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the Vaccine SAE Reporting Form and the Exposure During Pregnancy 
Supplemental Form, as applicable, regardless of whether there is an associated SAE.  In the 
event of an EDP, the information submitted should include the anticipated date of delivery.  
Since the information does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the ISF.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
are as follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.
8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
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8.3.8. Adverse Events of Special Interest
This section provides information on adverse events of special interest (AESIs) that may be 
detected during the study.
For infant participants:38

Preterm birth (born at <37 weeks’ gestation)

Birth weight 1001 to 2500 g

Developmental delay*

Positive viral (PCR or antigen-based) testing for SARS-CoV-2, when not reported 
during a MA-RTI visit, should be reported as SARS-CoV-2 test positive
The following AESIs are to be reported as SAEs:

Extremely preterm birth (<28 weeks)

Extremely low birth weight (≤1000 g)
For maternal participants:

Preterm delivery

Positive viral (PCR or antigen-based) testing for SARS-CoV-2, when not reported 
during a MA-RTI visit, should be reported as SARS-CoV-2 test positive
All AESIs must be reported as an AE or SAE following the procedures described in
Section 8.3.1 through Section 8.3.4 except the active collection period for AESIs is from the 
signing of the ICD until the end of the study for maternal participants and from birth until the 
end of the study for infant participants.
Notes: An AESI that is recorded as an SAE must be reported using the Vaccine SAE 
Reporting Form.
* Developmental delay is to be assessed by clinical expertise using local guidelines for 
standard of care. Events identified as both an AESI and an NDCMC should be reported as an 
AESI in the CRF.
8.3.8.1. Lack of Efficacy
This section is not applicable for this study, as efficacy is yet to be demonstrated in the study 
population.
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8.3.9. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 4.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 2 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 4.
8.3.9.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  Follow-up applies to all participants, including 
those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
Information will be provided to the sponsor as described in the IP manual. 
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
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8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration by an incorrect route;

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
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In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any additional dose of investigational product will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose in the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
No interruptions or dose modifications will be made in this study. 
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
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8.9. Health Economics
Health economics will be evaluated in exploratory analyses assessing vaccine impact on 
healthcare resource utilization parameters evaluated during study visits, which may include 
the following: number and type of medical visits, length of hospital stay, requirement for 
mechanical ventilation, requirement for respiratory diagnostic procedures, requirement for IV 
fluids, requirement for prescriptions, and antibiotic use. 
8.10. Procedures – Maternal Participants
8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to Vaccination to Day 1 –
Visit 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant or their parent(s)/legal 
guardian (if a minor). Each signature on the ICD must be personally dated by the signatory.
Maternal participants who might be illiterate must thumbprint the ICD and it must be signed 
and dated by an impartial witness who was present throughout the entire informed consent 
process before performing any study-related procedures.
The investigator or his or her designee will also sign and date the ICD.  A copy of the 
signed/thumbprinted and dated ICD must be given to the maternal participant and her 
parent(s)/legal guardian (if a minor).  The source data must reflect that the informed 
consent was obtained before participation in the study.
If the maternal participant is found ineligible for the study based on a full assessment of 
inclusion and exclusion criteria, the investigator may advise the participant and her 
parent(s)/legal guardian (if a minor), either by telephone or face to face, that the participant 
will be excluded from further participation in the study, as defined in Section 5.4.  All 
eligible maternal participants will proceed to complete the vaccination visit.
Standard-of-care procedures performed prior to informed consent can be considered for use 
in the study provided they follow guidance around the timing of procedures stipulated in the 
protocol.
In countries/locales where procedures to confirm maternal participant eligibility for
this clinical trial are not routinely performed, the procedures must be obtained and 
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.
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The following procedures will be performed:

Obtain written informed consent, and assent if appropriate, from the maternal participant
before performing any study-specific procedures. If the maternal participant is illiterate,
she must thumbprint the ICD and it must be signed and dated by an impartial witness 
who was present throughout the entire informed consent process.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity).  The date of birth will be 
collected to critically evaluate the immune response and safety profile by age.

Obtain and record current/former alcohol, tobacco, marijuana, or any illicit drug usage.

Obtain and record any medical, surgical, and obstetric history of clinical significance 
including history from prior and current pregnancy(ies).

Record the LMP and estimated delivery date (EDD).

Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.

Record the prepregnancy BMI in the source documentation. If the prepregnancy BMI is 
not available, record the BMI at the time of the first obstetric visit during the current 
pregnancy. 

Perform targeted physical examination evaluating/noting any clinically significant 
abnormalities within the following body systems: 
o
Mandatory - general appearance; heart; lungs; abdomen.
o
Discretionary - skin; head, eyes, ears, nose, and throat; musculoskeletal; 
extremities; neurological; lymph nodes.  
Note: Significant medical and surgical history and abnormal observations from 
the physical examination will be documented and recorded in the CRF.

Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement.
o
Where an obstetric ultrasound examination is not performed at ≥18 weeks of 
pregnancy as part of prenatal standard of care, perform an ultrasound examination.
o
Note: Physical or obstetric examinations performed as standard of care may be 
admissible if performed within 7 days prior to the vaccination visit.
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
Obtain details of any Ig (including monoclonal antibodies or immune globulin [Rho(D) 
immune globulin, eg, RhoGAM]) or blood products (eg, whole blood, packed cells) given 
at any time during the current pregnancy.

Obtain details of any nonstudy vaccinations given at any time during the current 
pregnancy.

Obtain details of syphilis, HIV, and HBV status.

Note: Only participants with a documented negative syphilis test result and negative 
HIV antibody and HBV surface antigen test results obtained during the current 
pregnancy are eligible for randomization. 

If not performed as standard of care, assessment should be performed as part of the 
study, locally, and vaccination of maternal participant should be deferred until the 
results are available and confirmed to be negative within 28 days prior to study 
randomization.

Ensure and document that all the inclusion criteria and none of the exclusion 
criteria are met.

Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.2.3.

Issue the maternal participant an e-diary and provide instructions on its completion
(if applicable). Note: eDiary completion instructions may be provided to her 
parent(s)/legal guardian (if a minor).

Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures, and provide instructions on their use to the maternal 
participant and her parent(s)/legal guardian (if a minor).

On the day of and prior to vaccination, ask the maternal participant to capture the 
baseline systemic event measurements in her e-diary or the site staff will capture the 
baseline systemic event measurements in the provisioned device (if applicable for 
illiterate participants).

Prior to vaccination, collect a blood sample of approximately 15 mL for serologic 
assessments (prevaccination blood collection should take place on the same day or within 
7 days before the vaccination visit).

Obtain the maternal participant’s randomization number and investigational product kit 
number using the IRT system. Refer to the IRT manual for further instructions on this 
process.
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
Qualified site staff member(s) will administer a single-vial dose of investigational 
product into the deltoid muscle of the (preferably) nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
Please refer to the IP manual for further instruction on this procedure.

Site staff must observe the maternal participant for any acute reactions for at least 
30 minutes after investigational product administration.

Record any acute reactions in the maternal participant’s source documents, on the AE 
page of the CRF, and on the Vaccine SAE Reporting Form as applicable.

Ask the maternal participant to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination, OR explain to the maternal participant that a study staff 
member/field worker will call or visit her every day from Day 2 to Day 7 after 
vaccination (where Day 1 is the day of vaccination) to collect or take her temperature and 
record systemic events, acute local reactions, and use of antipyretic medication in a diary
(if applicable).

Ask the maternal participant or her parent(s)/legal guardian (if a minor) to contact the site 
staff or investigator immediately if she experiences any of the following from Day 1 to 
Day 7 after vaccination to determine if an unscheduled reactogenicity visit is required as 
detailed in Section 8.10.5 OR inform the maternal participant or her parent(s)/legal 
guardian (if a minor) that if she experiences any of the following from Day 1 to Day 7 
after vaccination or is taking antipyretic medication at Day 7, then the study staff/field 
worker will continue to visit until resolution.  Furthermore, the maternal participant will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns as detailed in Section 8.10.5.

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring >20 measuring device units 
(greater than 10 cm).

Severe pain at the injection site.

Any severe systemic event.

Inform the maternal participants or her parent(s)/legal guardian (if a minor) that if a 
temperature of ≥38.0°C (≥100.4°F) is recorded during the collection of diary data, she 
will be required to have a rapid test for malaria as per local practice and details will be 
recorded in the diary (if applicable, based on local practice).

Remind maternal participants or her parent(s)/legal guardian (if a minor) that study staff 
may contact them to obtain additional information on events entered into the e-diary.
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
Remind maternal participants or their parent(s)/legal guardian (if a minor) to inform the 
study staff of any AEs and SAEs that occur for the duration of the trial as described in 
Section 8.2 and Section 10.2.

Remind the maternal participant or her parent(s)/legal guardian (if a minor) to bring the 
completed e-diary to the next visit (if applicable). 

Complete the source documents.

The investigator or an authorized designee completes the CRFs and the blinded 
dispenser/administrator completes the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.

Maternal participants or their parent(s)/legal guardian (if a minor) will be instructed to 
contact the site to report any significant illness (new or worsening), any medically 
attended respiratory events (eg, doctor’s visit, emergency room visit), or any 
hospitalization that occurs during the study period as detailed in Section 8.10.6.

Request the maternal participant and her parent(s)/legal guardian (if a minor) to contact 
the site if she goes into labor/is admitted to the maternal unit (The study staff/field worker 
will contact the maternal participant prior to the next study visit to remind her, if 
applicable).
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After Vaccination)
If delivery occurs before this visit, this visit will not be conducted.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

Review the participant’s e-diary data. Collect stop dates of any e-diary events ongoing 
on the last day that the e-diary was completed and record stop dates in the CRF.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.
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
Record AEs and SAEs as described in Section 8.2 and Section 10.2. Note: Active 
elicitation and collection of AEs and SAEs through 28 days after vaccination must occur 
even if delivery occurs within 28 days after vaccination.

The investigator or an authorized designee completes the CRF.

Maternal participants and their parent(s)/legal guardian (if a minor) will be instructed to 
contact the site to report any significant illness (new or worsening), any medically 
attended respiratory events (eg, doctor’s visit, emergency room visit), or any 
hospitalization that occurs during the study period as detailed in Section 8.10.6. 

Request the maternal participant and her parent(s)/legal guardian (if a minor) to contact 
the site if she goes into labor/is admitted to the maternal unit (The study staff/field worker 
will contact the maternal participant prior to the next study visit to remind her, if 
applicable).
8.10.3. Delivery (Maternity Unit)
The delivery visit spans the time from when a participant is admitted in labor through 
discharge following delivery of her infant. Protocol-specified procedures associated with 
this delivery visit may be done at any time during this period.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

If available, record the maternal participant’s group B streptococcal (GBS) status and if 
any medication was given for intrapartum antibiotic prophylaxis (IAP). Note: Positive 
GBS carriage should not be reported as an adverse event in the CRF if performed in the 
setting of routine prenatal care.

Record details of any nonstudy vaccinations given since the last visit.

Collect a blood sample of approximately 15 mL for serologic assessments.  Note: The 
maternal participant’s blood sample can be taken at any time during the delivery visit, 
preferably before delivery. In the event that the blood sample cannot be obtained 
before delivery, the sample should be collected as close to delivery as possible and at 
most 48 hours postpartum.
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments 
must also be collected.  Cord blood is collected from the umbilical cord vein attached to 
the placenta prior to the blood clotting within the cord and after the umbilical cord has 
been clamped and cut.  This sample should be labeled with the infant’s participant ID 
number.
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
Record pregnancy outcome information, including vital status of the infant (live, 
stillbirth, etc), mode of delivery (vaginal delivery or cesarean section), and the use of any 
assisted devices (forceps or vacuum).

Record details of any MA-RTI, including the diagnosis. 

Record AEs as described in Section 8.2 and Section 10.2.

Ask the maternal participants and her parent(s)/legal guardian (if a minor) to contact the 
site to report any significant illness (new or worsening), any medically attended 
respiratory events (eg, doctor’s visit, emergency room visit), or any hospitalization that 
occurs during the study period as detailed in Section 8.10.6.

Ask the maternal participant and her parent(s)/legal guardian (if a minor) to contact the 
site staff or investigator if her newborn infant meets the MA-RTI study criteria OR the 
study staff/field worker will contact the maternal participant/legal guardian(s) weekly to 
remind them to report any MA-RTI (if applicable).

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 210 Days After 
Delivery)

Obtain details of any postnatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [eg, HBIG]) or Rho(D) immune globulin [eg, RhoGAM]) or blood 
products (eg, whole blood, packed cells) given since the last visit.

Record details of any nonstudy vaccinations given since the last visit.

Record details of any MA-RTI, including the diagnosis.

Ask the maternal participant and her parent(s)/legal guardian (if a minor) to contact the 
site staff or investigator if her infant meets the MA-RTI study criteria OR the study 
staff/field worker will contact the maternal participant/legal guardian(s) weekly to remind 
them to report any MA-RTI, if applicable.

Record AEs as described in Section 8.2 and Section 10.2.

Complete the maternal participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.10.5. Unscheduled Reactogenicity Visits
If the maternal participant or her parent(s)/legal guardian (if a minor) reports 1 or more of the 
following, a contact must occur as soon as possible between the maternal participant and the 
investigator, or a medically qualified member of the study site staff, to assess if an 
unscheduled reactogenicity visit is required OR based on local practice in certain 
countries/locales, maternal participants will be referred to the appropriate healthcare facility 
at the discretion of the study staff/field worker if there are any concerns regarding 
reactogenicity events, including:

redness at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

swelling at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

severe injection site pain on the arm that the investigational product was 
administered, 

fever ≥39.0°C (≥102.1°F).
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The maternal participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or

The participant/study staff/field worker recorded an incorrect value in the e-diary 
(confirmation of an e-diary data entry error), or

The investigator or appropriate designee determines that the visit is not required.
This contact will be recorded in the maternal participant’s source notes and in the CRF.
Any ongoing reactions must be assessed at the next scheduled visit.
The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure oral temperature.

Measure the participant’s heart rate.

Measure the participant’s blood pressure (seated).
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
Measure the minimum and maximum diameters of redness (if present) on the arm in 
which the investigational product was administered.

Measure the minimum and maximum diameters of swelling (if present) on the arm in 
which the investigational product was administered.

Assess if necrosis is present at the injection site on the arm in which the investigational 
product was administered.

Assess if any exfoliative dermatitis is present.

Assess any injection site pain on the arm in which the investigational product was 
administered that is present in accordance with the reactogenicity grading scale provided 
in Section 8.2.1.1.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 8.2.1.2.

Ask the participant or her parent(s)/legal guardian (if a minor) if she attended an 
emergency room visit or was hospitalized.

For severe pain at the injection site resulting in an emergency room visit or 
hospitalization, severe systemic events associated with an emergency room visit or 
hospitalization, any necrosis on the arm in which the investigational product was 
administered, or exfoliative dermatitis, the investigator or qualified designee must assess 
these events in accordance with the intensity AE grading scale provided in
Section 8.2.1.1 and Section 8.2.1.2.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

Complete the participant’s source documents.

The investigator or an authorized designee will complete the CRFs.

The study staff/field worker may contact the participant to obtain additional information 
on events entered into the e-diary, as appropriate.
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8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria – Maternal 
Participants

Starting from Day 1 after vaccination (where Day 1 is the day of vaccination) until the 
end of the study, all maternal participants will be monitored for MA-RTIs as detailed in 
Section 1.2.3.1 and Section 8.1.2. Maternal participants or their parent(s)/legal guardian 
(if a minor) should notify the site and/field worker of the occurrence of any MA-RTIs 
immediately but no later than the next study visit. Note: Site contact may be by an 
electronic method of communication (including but not limited to electronic messaging, 
short message service [SMS], text, email), by phone call, or by face-to-face contact.

The definition of maternal RTI includes 1 or more of the following signs and/or 
symptoms:
o
New or increased sore throat
o
New or increased cough
o
New or increased nasal congestion
o
New or increased nasal discharge
o
New or increased wheezing
o
New or increased sputum production
o
New or increased shortness of breath

Record the details of any MA-RTI, including the diagnosis, the medically attended visit 
location (hospital, outpatient visit, emergency room, urgent care, or home visit), duration 
of hospitalization, intensive care unit (ICU) duration if applicable, prescribed medications 
for the MA-RTI, assessments including RSV test result (eg, NAAT, rapid antigen 
detection tests, or any other molecular diagnostic test), if available, and the final 
diagnosis.

Record the details of any nonstudy vaccinations.

Record AEs as described in Section 8.2 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.11. Procedures – Infant Participants
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After Birth)

Manually assign a single infant participant identifier. This will be assigned manually by 
the site using the following convention: the infant participant’s identifier will be the 
maternal participant’s IRT-generated numeric ID but with the fifth digit changed to a 2 
(eg, if the maternal participant is given number 10011001, then the infant will be 
10012001).

Collect a cord blood sample of approximately 10 mL for immunogenicity assessments.  
Cord blood is collected from the umbilical cord vein attached to the placenta prior to the 
blood clotting within the cord and after the umbilical cord has been clamped and cut.  
This sample should be labeled with the infant’s participant ID number.

If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 24 hours, but up to 7 days after birth.  The volume of blood collected 
will be based on the weight of the infant (refer to Table 3).

Ensure and document that all the infant inclusion criteria and none of the infant exclusion 
criteria are met.

Collect demography (including complete date of birth [ie, dd-Mmm-YYYY], sex, race, 
and ethnicity).  The date of birth will be collected to critically evaluate the immune 
response.

Obtain and record the infant’s length, head circumference, and weight at birth.

Obtain and record the infant’s birth data, including GA and appearance, pulse, 
grimace, activity, and respiration (Apgar) score. 

Obtain and record background factors as described in Section 10.5.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.

Standard-of-care vital signs and examination procedures can be considered for use in 
the study provided they were performed within 72 hours after birth. Note: Please 
reference the physical examination procedures below for details. 

Perform a physical examination, if not performed as part of standard of care, noting 
any clinically significant abnormalities within the following body systems: general 
appearance; skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; back; 
musculoskeletal; extremities; genitourinary; neurological; and lymph nodes.  
Abnormal results must be recorded on source documents as well as the physical 
examination pages of the CRF; only if the abnormal finding is deemed to be clinically 
significant should this be recorded on the AE pages of the CRF. 
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
Record details of any congenital anomalies on the AE page of the CRF, and report 
as an SAE as described in Section 10.2.3.

Record any medication as described in Section 6.5.6.

Obtain details of any Ig (including monoclonal antibodies [eg, Synagis] or immune 
globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given to the 
infant participant since birth.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Review the weekly contact schedule with the parent(s)/legal guardian(s) and collect 
contact information OR remind the parent(s)/legal guardian(s) that a field worker will 
contact them weekly to remind them to report any MA-RTI (if applicable).

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria. An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of this study visit.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate. Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the
study visit.
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
Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the site source documents. Newly 
identified abnormal findings must be recorded on source documents and, if considered 
clinically significant in the judgment of the investigator/examiner, on the AE page of the 
CRF. Note: Standard-of-care examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee 
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria.  An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every 7 days 
from birth until the 6-month follow-up visit to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The weekly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.7.1 for guidance on reported cases of 
MA-RTIs in infant participants during the first 6 months after birth. 
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8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.

Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.
Note: Standard-of-care examination procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Ask the parent(s)/legal guardian(s) to contact the investigator immediately if any 
significant illness or hospitalization occurs or if the infant meets the MA-RTI visit
criteria.  An RTI study visit, along with a nasal swab collection, must be performed 
for all hospitalizations due to an RTI and severe MA-LRTIs as described in 
Section 1.2.4.1 and Section 8.11.8.
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
If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care as 
described above, noting any clinically significant abnormalities in the source documents. 
Newly identified abnormal findings must be recorded on source documents and, if 
considered clinically significant in the judgment of the investigator/examiner, on the AE 
page of the CRF. Only applicable if a clinic visit is conducted. Note: Standard-of-care 
examination procedures can be considered for use at this study visit, if they were 
performed within the window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants except for infant participants born during the first year of the study.

The investigator or an authorized designee completes the CRF for infant participants born 
during the first year of the study. Note: An additional 12-month blinded follow-up period 
for longer-term RTI surveillance and safety oversight will be included for these 
participants.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Confirm the understanding of the infant participant’s parent(s)/legal guardian(s) 
regarding site contact for the study, which is approximately every month (28 to 35 days) 
until the end-of-study visit. Ask the parent(s)/legal guardian(s) to contact the 
investigational site/field worker promptly if the infant meets the MA-RTI visit criteria.  
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The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days After Birth; 
Infant Participants Born During the First Year of the Study Only)

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 
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Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 742 Days After 
Birth; Infant Participants Born During the First Year of the Study)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if 
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care, noting 
any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF. 
Only applicable if a clinic visit is conducted. Note: Standard-of-care examination 
procedures can be considered for use at this study visit, if they were performed within the 
window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents. 

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants born during the first year of the study.
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8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 Months After 
Delivery)

This is an active surveillance period spanning from birth through 6 months after delivery 
(Visit 3). Note: Reporting MA-RTI events should commence 72 hours after the infant’s 
delivery.  Respiratory distress events associated with and within 72 hours of birth should 
not be captured as MA-RTI events for the study but should be captured as AEs/SAEs 
(if applicable).

The sponsor may alter the frequency of the weekly contacts or the duration of 
surveillance for MA-RTI based on RSV surveillance data or other operational factors.
8.11.7.1. Study Visits Following a Medically Attended RTI – Hospital, Home, or Clinic 
Visit

Contact the infant participant’s parent(s)/legal guardian(s) approximately every week 
(7 to 10 days) from birth until Visit 3 (6-month follow-up visit), to remind the 
parent(s)/legal guardian(s) to contact the investigational site promptly if the infant meets 
the criteria for an MA-RTI event.  The weekly contact may be via the e-diary device or 
study-related mobile application, text, email, phone call, or face-to-face contact with the 
site staff/field worker. Please refer to Table 1 regarding clinical signs and symptoms that 
meet the study definition of an MA-RTI, and Section 1.2.4.1 for study-required 
assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by:
o
The infant caregiver during or within 10 days following the MA-RTI visit
OR
o
The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an event requiring a visit to a healthcare provider, the site staff 
and/field worker should confirm, based on information provided, whether the event meets 
the criteria for an MA-RTI. Please refer to Table 1 and Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

When an infant MA-RTI criterion is met or confirmed, the site/field worker will obtain 
records from the medically attended visit and record the healthcare information as 
detailed in Appendix 6.
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When an infant MA-RTI criterion is met or confirmed, the infant participant will be 
seen as soon as possible and optimally within 72 hours or up to 10 days for an RTI study 
visit by the investigational site staff or qualified designee. 

The infant participant may be seen either at the time of the MA-RTI, at home or at the 
study site (if discharged), or if the infant participant has been hospitalized or is receiving 
treatment at another medical facility, the site staff/field worker can conduct the RTI study 
visit at those facilities.
o
If the RTI study visit is not performed within 72 hours of the event, it should still be 
performed, including the collection of nasal swab specimens. 
o
Targeted assessments at an RTI study visit include but are not limited to:
o
Respiratory signs: lower chest wall indrawing.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Nasal swab collection from the infant participant for testing at the central 
laboratory.
o
Body weight

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site/field worker if the infant’s 
illness worsens, or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for the event as detailed in Section 8.1.
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8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit Criteria

This is a long-term surveillance procedure for all infant participants from 6 months after 
delivery (Visit 3) until the last study visit.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) from Visit 3 (6-month follow-up visit) until the end-of-study visit, to 
remind the parent(s)/legal guardian(s) to contact the investigational site promptly if the 
infant meets the criteria for an MA-RTI visit.  The monthly contact may be via the 
e-diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by: 
o
The infant caregiver during or within 10 days following the MA-RTI visit
OR
o
The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an MA-RTI, the site should obtain additional information and 
determine whether the event also meets the study definition of a severe MA-LRTI.
o
Note: Severe MA-LRTI is defined in Table 1.

The site/field worker will obtain records from the medically attended visit and record the 
healthcare information as detailed in Appendix 6.

When an infant MA-RTI criterion is confirmed and also meets the study definition of 
hospitalization due to an RTI or a severe MA-LRTI, the infant participant will be seen 
as soon as possible and optimally within 72 hours or up to 10 days for an RTI study 
visit that includes a nasal swab collection by the investigational site staff/field worker. 
The staff/field worker will obtain the nasal swab optimally within 72 hours or up to 
10 days of the event with the infant participant either at home (if discharged) or, if the 
infant participant has been hospitalized or receiving treatment at another medical facility, 
the site staff/field worker will conduct the visit at those facilities.
o
Note: Nasal swab collection from the infant participant is for testing at the central 
laboratory.
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A targeted RTI study visit will be required for all reported cases of hospitalization due to 
an RTI or severe MA-LRTI only, and this includes but is not limited to:
o
Respiratory signs: lower chest wall indrawing, failure to respond/unconsciousness.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Body weight

A targeted RTI study visit is not required for an MA-RTI event not meeting the definition 
of hospitalization due to an RTI or severe MA-LRTI.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the MA-RTI event, including emergency room or
hospitalization details with admission and discharge date (if applicable).

Record any medication as described in Section 6.5.6.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.  Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site if the infant’s illness worsens, 
or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Compile the adjudication submission package for hospitalizations due to an RTI and 
severe MA-LRTI events only as detailed in Section 8.1.
8.12. Nasal Swab Collection
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI 
visit during the RSV surveillance period from 72 hours after delivery until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of an MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1).
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The nasal swab sample is to be collected as soon as possible and optimally within 72 hours or 
up to 10 days of an MA-RTI visit in either the infant participant’s home or a medical setting 
(eg, clinic, hospital, etc) by the investigational site staff. 
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), the 
nasal swab can be collected by the infant’s caregiver or the HCP assessing the infant 
(in addition to any samples obtained in the course of routine clinical care) for processing at a 
Pfizer central laboratory, as detailed in Section 8.11.7.1 and Section 8.11.8.
In the event that these restrictions prevent taking RTI study swabs at the investigational site, 
the infant’s caregiver will be given a study nasal swab collection kit including shipping 
instructions, to be used if necessary. The infant caregiver or the HCP assessing the infant 
during an MA-RTI visit may assist the investigational sites by collecting of the study nasal 
swab samples, as required.
Note: Investigational site staff will review the procedures for nasal swab sample collection 
and shipping instructions with each infant caregiver and ensure that he/she understands the 
appropriate procedures for collecting and packaging samples for shipment to the study site.
The process for nasal swab collection and transport to the Pfizer central laboratory via study 
sites is detailed in the ISF.
8.13. Communication and Use of Technology
In a study of this duration that is event-driven, it is vital to ensure that communication 
between the study site and the maternal participant and parent(s)/legal guardian(s) is 
maintained to ensure that endpoint events are not missed.  This study will employ various 
methods, tailored to the individual participant (maternal and/or infant participant), to ensure 
that communication is maintained and study information can be transmitted securely.  Using 
appropriate technology, a communication pathway between the maternal participant and 
parent(s)/legal guardian(s) and the study site staff will be established.  The maternal 
participant and the parent(s)/legal guardian(s) may be able to utilize their own devices to 
access this technology, or use a device provided by the sponsor.  Traditional methods of 
telephone communication will also be available. The technology solution may facilitate the 
following:

Contact with the investigator.

The ability of the maternal participant/parent(s)/legal guardian(s) to report MA-RTI visits
associated with the infant participant.

An alert in the event that the maternal or infant participant is hospitalized.

Visit reminders.
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
Messages of thanks and encouragement from the study team.

A platform for recording local reactions and systemic events (e-diary).
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in an SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Estimands and Statistical Hypotheses
The null hypothesis to be tested concerns VE for the primary endpoints. The RSV vaccine 
will be compared to placebo, testing the hypotheses H0: VE ≤20% vs Ha: VE 20%. For all 
secondary efficacy endpoints, the RSV vaccine will be compared to placebo, testing the 
hypotheses H0: VE ≤0% vs Ha: VE >0%. Hypothesis testing of the secondary endpoints is 
conditional upon rejection of the null hypothesis for at least 1 of the primary endpoints.
9.1.1. Estimands – Infant Participants
9.1.1.1. Efficacy
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with key protocol criteria (evaluable participants): 

VE, defined as the percentage relative risk reduction in the incidence of MA-LRTI due to 
RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of severe MA-LRTI 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of hospitalization 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of all-cause 
MA-LRTI in the RSV vaccine group, relative to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  For participants who 
discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
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9.1.1.2. Immunogenicity
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with the key protocol criteria (evaluable participants):

Functional antibody levels estimated by the GMT for RSV A and RSV B serum
neutralizing titers.

Geometric mean ratio (GMR), estimated by the ratio of the GMTs for RSV A and RSV B
serum neutralizing titers of the RSV vaccine group to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as missing completely at random (MCAR) is assumed.  For participants 
who discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.3. Safety
In infant participants born to the maternal participants receiving 1 dose of investigational 
product:

The percentage of infant participants with specific birth outcomes.

The percentage of infant participants having AEs from birth through 1 month of age.

The percentage of infant participants having SAEs, NDCMCs, and new diagnosed 
congenital anomalies from birth through the last study visit.
Missing AE dates and missing AE intensity will be handled according to Pfizer safety rules.
9.1.2. Estimands – Maternal Participants
9.1.2.1. Immunogenicity
In maternal participants receiving 1 dose of investigational product and in compliance with 
the key protocol criteria (evaluable participants):

The immune response, estimated by the GMT for RSV A and RSV B serum neutralizing 
titers.

The immune response, estimated by the GMFR from baseline in RSV A and RSV B 
serum neutralizing titers.

GMR, estimated by the ratio of the GMTs for RSV A and RSV B serum neutralizing 
titers of the RSV vaccine group to the placebo group.
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
Geometric mean of the IgG levels against RSV prefusion F.

Geometric mean of the Ig levels to nonvaccine RSV antigens.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as MCAR is assumed.  For participants who discontinue from the study 
or have major protocol violations, all postdiscontinuation or postviolation observations will 
be censored.
9.1.2.2. Safety
In maternal participants receiving 1 dose of investigational product:

The percentage of maternal participants reporting AEs through 1 month after vaccination.

The percentage of maternal participants reporting obstetric complications and SAEs 
through the end of the study.

The percentage of maternal participants reporting local reactions within 7 days of 
vaccination.

The percentage of maternal participants reporting systemic events within 7 days of 
vaccination.
Missing e-diary data will not be imputed; missing AE dates and missing AE intensity will be 
handled according to Pfizer safety rules.
9.2. Sample Size Determination
This is an event-driven study. Sample size is determined as the number of participants to be 
randomized that is expected to accrue the required number of primary endpoint cases in the 
evaluable population. In this study there are 2 primary endpoints, and success on either 
primary endpoint is sufficient (see Section 9.1); power for the study overall is therefore at 
least as high as the power for either primary endpoint individually. In order for the study to 
have at least 90% power to reject the null hypothesis for MA-LRTI due to RSV when true 
VE is 60%, a total of 124 cases of MA-LRTI due to RSV within 90 days of birth are required 
in the evaluable population. This also accounts for potential use of an alpha of 1.25% 
1-sided within the multiplicity adjustment. There is no explicit case target for the endpoint of 
severe MA-LRTI due to RSV; depending on the assumed true VE, power for that individual 
hypothesis may be lower, but the power for the primary endpoint family will be at least 90%. 
Hypotheses about VE may be restated as hypotheses about the proportion of cases in the 
RSV vaccine group, conditional upon a fixed total number of cases. If this proportion is p, 
the null hypothesis H0: VE ≤20% is equivalent to H0: p ≥0.444; the assumption of VE = 60% 
corresponds to p = 0.286. Power was evaluated by the exact binomial test, and the case 
target established as that number k for which power is guaranteed to be at least 90%, for all 
k* ≥k. The calculation accounted for the study design (1:1 randomization of participants to 
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RSV vaccine : placebo), planned interim analyses of efficacy (see Section 9.5), and an 
overall type 1 error of 2.5% 1-sided across the 2 primary endpoints. 
This global study is planned to be conducted in the United States and other high-income 
countries as well as LMICs. Incidence rates of the primary endpoints are expected to vary in 
different regions. Based on a recently completed Phase 3 trial of an RSV vaccine, the 
assumed incidence rate for MA-LRTI due to RSV through 90 days in low-incidence 
countries, such as the United States, is approximately 1.75%; and in other regions,
approximately 3.90%. With these assumptions, and also allowing for 60% VE and 10% of 
enrolled participants being nonevaluable, enrollment of approximately 6900 participants is 
planned for the study as a whole. The exact number of participants required to accrue the 
case target may be higher or lower than this, depending on incidence rates, observed VE, and 
the proportion of participants evaluable.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined for infant and maternal 
participants:
Population
Description
Enrolled 
All maternal participants who sign the ICD.
Randomly assigned to 
investigational product
All maternal participants who are assigned a randomization 
number in the IRT system.
Evaluable efficacy –
infant (per-protocol)
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized at least 14 days prior to delivery, did not 
receive palivizumab or another monoclonal antibody targeting 
RSV, have no major protocol violations, and did not have 
transfusions of more than 20 ml/kg of any blood products at 
<180 days. 
Modified intent-to-treat 
(mITT) efficacy – infant
All infant participants who are born to vaccinated maternal 
participants.
Evaluable 
immunogenicity – infant
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized, have blood drawn for assay testing 
within the specified time frame, have valid and determinate 
assay results for the proposed analysis, and have no major 
protocol violations. 
Evaluable 
immunogenicity –
maternal
All maternal participants who are eligible, receive the 
investigational product to which they were randomized, have 
blood drawn for assay testing within the specified time frame, 
have valid and determinate assay results for the proposed 
analysis, and have no major protocol violations. 
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Population
Description
mITT immunogenicity –
infant
All infant participants who are born to vaccinated maternal 
participants and have at least 1 valid and determinate assay 
result for the proposed analysis.
mITT immunogenicity –
maternal
All randomized maternal participants who receive 
investigational product and have at least 1 valid and determinate 
assay result for the proposed analysis. 
Safety – infant
All infant participants who are born to vaccinated maternal 
participants.
Safety – maternal
All randomized maternal participants who receive 
investigational product.
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock for the first planned analysis 
and will describe the participant populations to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data.  This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The analysis of efficacy will use a conditional exact test based on the 
binomial distribution of the number of disease cases in the RSV vaccine 
group, given the total number of cases in both groups. The incidence of 
MA-LRTI due to RSV and severe MA-LRTI due to RSV in infant 
participants will be evaluated in both groups up to 90 days, 120 days, 
150 days, and 180 days after birth.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population. 

The 2 primary endpoints of MA-LRTI due to RSV and severe 
MA-LRTI due to RSV will be tested in parallel using a multiplicity 
adjustment procedure. Success of the trial requires rejection of the null 
hypothesis (ie, a CI lower bound >20%) for either one of the 2 primary 
endpoints.

The primary endpoint of severe MA-LRTI due to RSV may be demoted 
to a secondary endpoint, if there are insufficient cases for an adequately 
powered analysis. During the trial, blinded accrual of cases will be 
monitored and prior to any unblinding, a decision rule for this change 
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will be established based on the total number of cases of severe 
MA-LRTI due to RSV.

Testing of the 2 primary endpoints across the time intervals will follow a 
fixed sequence with a gatekeeping strategy. First, the hypothesis 
pertaining to the incidence of the 2 primary endpoints within 90 days 
after birth will be tested, at the full multiplicity-adjusted alpha level, 
using a multiplicity adjustment for the 2 endpoints. If that null 
hypothesis cannot be rejected, testing ends. Otherwise, testing proceeds 
to the incidence within 120 days after birth. Only primary endpoint(s)
that are successful at all earlier time intervals will be considered at 
subsequent intervals. Testing will proceed to the endpoints evaluated at 
150 days and 180 days, conditional on rejection of the null hypotheses 
for all earlier time intervals. Refer to the SAP for full details of the 
testing sequence and multiplicity correction strategy.

There may be up to 2 interim analyses of the MA-LRTI-due-to-RSV
endpoint when there is an adequate number of cases (at least 43 cases
within 90 days). Based on the fraction of cases included in an interim 
analysis, an alpha level will be derived based on a Lan-DeMets
implementation of the O’Brien-Fleming alpha spending function. For 
example, if there are 2 interim analyses at 43 cases and 62 cases, the 
appropriate 1-sided significance levels are 0.00014 at the first interim 
analysis, 0.0015 at the second interim analysis, and 0.0245 at the final 
analysis. Implementation of these 1-sided significance levels ensures the 
overall type 1 error for the primary endpoint will be no more than 0.025. 
See Section 9.5 for more details.

At the interim analyses there will also be an assessment for futility, based 
on conditional power for the MA-LRTI-due-to-RSV endpoint. If the 
probability of success at the end of the trial is low, given the interim 
analysis results and the initially assumed VE is applied to the remaining 
data, consideration will be given to stopping the study for futility.

CIs for VE will be calculated using the appropriate multiplicity-adjusted 
alpha level α. If the lower 100(1 - α)% confidence limit for VE exceeds 
20%, the null hypothesis for that endpoint will be rejected.

At the end of the trial, the RSV vaccine may be deemed efficacious if 
there are 43 or fewer cases of MA-LRTI due to RSV in the RSV vaccine 
group out of the 124 total primary endpoint cases.  This corresponds to 
estimated VE = 47% with 95.1% CI = (22%, 64%). For severe 
MA-LRTI, assuming a total of 50 cases occur, the vaccine may be 
deemed efficacious if there are 14 or fewer cases in the RSV vaccine 
group.  
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This corresponds to estimated VE = 61% with 95.1% CI = (26%, 81%).
For both of these examples, it is assumed a 1-sided alpha of 0.0245 
applies to the endpoint in question. A smaller multiplicity-adjusted alpha 
may apply, leading to a higher VE required for success. 

Kaplan-Meier curves showing accrual of primary endpoint cases over 
180 days will be presented.
Secondary

The analysis of secondary efficacy endpoints will use the exact
conditional binomial method, as for the primary endpoint. Secondary 
endpoints will be examined at the final analysis only. VE will be 
estimated along with 2-sided 95% CI. 

Inference for the secondary endpoints will be conditional upon 
demonstrating success for one of the primary efficacy endpoints. The 
secondary endpoints of hospitalizations due to RSV, all-cause MA-LRTI, 
and MA-LRTI beyond 180 days will be tested in parallel so as to 
preserve the overall type 1 error across primary and secondary endpoint 
families at no more than 2.5% 1-sided. Multiplicity correction strategies 
will be defined in the SAP. VE will be evaluated sequentially at 90 days, 
120 days, 150 days, 180 days, and 360 days for hospitalization due to 
RSV and all-cause MA-LRTI and at 210 days, 240 days, 270 days, and 
360 days for MA-LRTI due to RSV. Testing will only proceed to later 
time points conditional on success of all previous time points. 

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.
Exploratory

The incidence in infant participants of MA-RTIs due to RSV with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized.

The incidence in infant participants of MA-RTIs due to any cause with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized. All MA-RTIs and severe MA-LRTIs will be summarized 
separately.

The incidence in infant participants of MA-LRTIs due to RSV occurring 
361 to 730 days after birth will be summarized. 

The incidence in infant participants of severe MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized. 
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
The incidence in infant participants of hospitalization due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The primary endpoint through 180 days after birth will be summarized 
separately as cases associated with RSV subgroup A or RSV subgroup B 
infection.

The primary endpoint through 180 days after birth will be summarized 
by interval from vaccination to delivery and by GA at the time of 
vaccination.

The incidence of MA-RTI, MA-LRTI, and severe MA-LRTI due to RSV 
occurring 0 to 730 days after birth in premature infants (<37 weeks GA) 
will be summarized.

The incidence of MA-RTI due to any cause in maternal participants from 
vaccination through 180 days after delivery will be summarized. 
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

A 3-tier approach will be used to summarize AEs. For both Tier 1 and 
Tier 2 events, the 95% CIs for the difference in the percentage of 
participants reporting the events between the RSV vaccine group and the 
placebo group will be calculated using the test statistic proposed by 
Miettinen and Nurminen; in addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in the percentage of 
participants reporting the events, based on the same test statistic and under 
the assumption that the test statistic is asymptotically normally distributed.  
A Medical Dictionary for Regulatory Activities (MedDRA) preferred term 
is defined as a Tier 2 event if there are 1% or more participants in at least
1 vaccine group reporting the event.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
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dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Secondary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Exploratory 
Subgroup analyses of safety will be performed based on age at vaccination 
(18 years, ≥18 years). These and other exploratory analyses will be 
described in the SAP, finalized before first database lock.
9.4.3. Other Analyses 
9.4.3.1. Immunogenicity Analyses
Immunogenicity endpoints are exploratory in the study.  The analyses of immunogenicity 
endpoints will be based on the evaluable populations.  An additional analysis will be 
performed based on the mITT populations if there is enough difference between the mITT 
populations and the evaluable populations.  Immunogenicity data for maternal participants 
and infant participants will be summarized separately, with the exception of maternal-to-
infant placental transfer analysis.  Participants will be summarized according to the vaccine 
group to which they (for maternal participants) or their mothers (for infant participants) were 
randomized.
The secondary and exploratory immunogenicity endpoints will be described by the following 
summaries and the 95% CIs:

GMT of the RSV A and RSV B serum neutralizing titers at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMT of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMFR for RSV A and RSV B serum neutralizing titers from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).
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
GMFR of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMR of the RSV vaccine group to the placebo group for the RSV A and 
RSV B serum neutralizing titers at each available time point after vaccination (maternal 
participants and infant participants, separately).

GMR of the RSV vaccine group to the placebo group for the combined RSV A/B serum
neutralizing titers at each available time point after vaccination (maternal participants and 
infant participants, separately).

Geometric mean of the IgG levels against RSV prefusion F and Ig levels to nonvaccine 
RSV antigens at each available time point by vaccine group (maternal participants and 
infant participants, separately).

Geometric mean of IgG subclass levels (minimally IgG1) against RSV prefusion F at 
each available time point by vaccine group (maternal participants only).
Empirical reverse cumulative distribution curves (RCDCs) for combinations of time points 
and vaccine groups will be presented for RSV A and RSV B serum neutralizing titers.
A sensitivity analysis will be performed to exclude immunogenicity data from mothers and 
their infants following onset of RSV infection between vaccination and delivery (based on 
evidence from the nonvaccine antigen assay). 
Subgroup analyses of the secondary and exploratory immunogenicity endpoints will be 
performed, including an analysis based on GA at the time of vaccination, age at vaccination 
(18 years, ≥18 years), time from vaccination to delivery, and by country subcategories. All 
subgroup analyses will be defined in the SAP.
In addition, the maternal-to-infant placental transfer ratio (infant/mother) of RSV A and 
RSV B serum neutralizing titers and associated 95% CI will be summarized.
9.4.3.2. Healthcare Utilization Analyses
Healthcare utilization endpoints are exploratory in the study; these analyses will be described 
in the SAP and finalized before first database lock. For these analyses, details of healthcare 
resource utilization for all infants will be assessed at each MA-RTI visit from 72 hours after 
the infant’s delivery through the last study visit (730 days after birth). Univariate summaries
of healthcare resource utilization variables will be compared between the RSVpreF and 
placebo groups. The summarized variables may include the following: number and type 
(eg, respiratory, reactive airway disease [RAD]/asthma/wheezing) of medical visits 
(eg, outpatient, urgent care, emergency room, hospitalization, ICU), length of hospital stay, 
requirement for mechanical ventilation (yes/no, total number of episodes, total number of 
hours/days on treatment), requirement for IV fluids, requirement for respiratory diagnostic 
procedures (eg, chest radiograph, supplemental oxygen, pulse oximetry), requirement for 
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prescriptions (eg, total number of prescriptions, selected respiratory medications 
[eg, bronchodilators, corticosteroid therapy, racemic epinephrine]), and antibiotic use 
(eg, total number of prescriptions, number of use days).
9.5. Interim Analyses
Interim analyses may be performed to assess efficacy and safety after at least 43 cases of 
MA-LRTI due to RSV within 90 days have occurred. Because of the relatively low number 
of cases of severe MA-LRTI due to RSV expected, the interim analyses may not consider 
that endpoint. Interim analysis results may be used for internal business decisions regarding 
future study planning, stopping for futility, or stopping for early success.
The order of cases included in the interim analysis will be determined by the adjudication 
committee as those first confirmed as meeting the protocol-defined criteria. When the target 
number of cases for an interim analysis is reached, it is possible that additional potential 
cases will be under adjudication. Only cases that have been fully adjudicated prior to taking a 
data snapshot will be included in an interim analysis.
The analysis of efficacy will utilize an O’Brien-Fleming alpha spending rule based on the 
fraction of cases of MA-LRTI due to RSV within 90 days available. The exact number of 
cases at each interim analysis is not fixed and may be decided based on operational reasons. 
However, no fewer than 43 cases will be included in the first interim analysis.  For example, 
to control the overall type 1 error for the primary endpoint at 2.5% 1-sided, a first interim 
analysis at 43 cases would use a 1-sided significance level of 0.014%. If a second interim 
analysis was performed-for example-at 62 cases, it would use a 1-sided significance level of 
0.15%. The final analysis at the target number of cases would use a 1-sided significance level 
of 2.45%. The alpha levels used at interim and final analyses will depend on the exact 
fraction of cases available at the interim analysis.
Testing of the primary endpoints at the interim analysis will follow the sequence of 
interval-specific tests as described in Section 9.4.1.  However, consideration will be given to 
stopping the study for efficacy only if all time intervals through 180 days indicate statistically 
significant efficacy. Secondary endpoints will not be tested at the interim analysis.
Futility will also be assessed using conditional power. Full details will be defined in the 
SAP. For example, if there are 62 cases available for the interim analysis, Table 7 indicates 
case splits for which stopping the study will be considered. The actual number of cases 
available may be slightly higher or lower than 62, and the decision rules amended 
accordingly.
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Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals at an 
Interim Analysis
Total Cases
RSV Vaccine 
Group Cases
Placebo Group 
Cases
VE (CI)a
Notes
43 (First interim)
24
19
-26% (-145%, 34%)
Conditional power 
<20%,b possible 
futility declaration
43 (First interim)
7
36
81% (23%, 97%)
Maximum number 
of vaccine group
cases permitted to 
declare VE >20%
62 (Second interim)
29
33
12% (-49%, 49%)
Conditional power 
<20%,b possible 
futility declaration
62 (Second interim)
15
47
68% (24%, 88%)
Maximum number 
of vaccine group
cases permitted to 
declare VE >20%
Abbreviation: VE = vaccine efficacy.
a.
Confidence level for efficacy declaration based on available alpha at each interim; 95% confidence level 
for futility.
b.
Other conditional power levels may be considered as a trigger for a futility decision.
Before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan, and method of maintaining the study blind as per Pfizer’s standard 
operating procedures (SOPs) will be documented and approved in the DMC charter.  In 
addition, the analysis details must be documented and approved in an interim analysis SAP 
or final SAP.
9.5.1. Data Monitoring Committee
This study will use an E-DMC.  Refer to the E-DMC charter for further details.
The E-DMC will review safety data at defined intervals as specified in the charter.  The 
E-DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.
The E-DMC may review unblinded data during closed meeting sessions; however, the 
sponsor will remain blinded and will not be permitted access to the randomization 
assignments until the database is locked and unblinded.
After each meeting, the E-DMC will make recommendations that may include continuing the 
study with or without modification or pausing or stopping vaccination for safety or other 
reasons.
The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
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decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints, to regulatory authorities, as appropriate.
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the maternal 
participant and her parent(s)/legal guardian (if a minor) and answer all questions regarding 
the study.
Maternal participants must be informed that their participation is voluntary.  Maternal 
participants and their parent(s)/legal guardian (if a minor) will be required to sign a statement 
of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant and her parent(s)/legal guardian (if a 
minor) is fully informed about the nature and objectives of the study, the sharing of data 
related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data. 
The participant and her parent(s)/legal guardian (if a minor) must be informed that his/her 
personal study-related data will be used by the sponsor in accordance with local data 
protection law.  The level of disclosure must also be explained to the participant.
The participant and her parent(s)/legal guardian (if a minor) must be informed that his/her
medical records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities.
The investigator further must ensure that each study participant or his or her parent(s)/legal 
guardian(s) is fully informed about his or her right to access and correct his or her personal 
data and to withdraw consent for the processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
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Participants and parent(s)/legal guardian(s) must be reconsented to the most current version 
of the ICD(s) during their participation in the study.
A copy of the ICD(s) must be provided to the maternal participant or the parent(s)/legal 
guardian(s).
A study-specific assent form will be provided to maternal participants denoted to be “minor 
participants” as required by local regulations.  It is to be understood as the “minor” maternal 
participants will participate in a trial after having received age-appropriate information and is 
sometimes also referred to as “knowing agreement.”  If the study includes minor participants 
who reach the age of majority during the study, as recognized under local law, they must 
reconsent as adults to remain in the study.  If the enrollment of emancipated minors is 
permitted by the study age criteria, the IRB/EC, and local law, they must provide 
documentation of legal status to give consent without the permission of a parent or legal 
guardian.
Before any study-specific activity is performed, the investigator, or a person designated by 
the investigator, will obtain written informed consent from each maternal participant and her 
parent(s)/legal guardian (if a minor).  This will include written informed consent for the 
mother and the fetus during the pregnancy, and the infant’s continuation in the study after 
delivery.  Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements.
Participants and their parent(s)/legal guardian (if a minor) who are rescreened may be 
required to sign a new ICD as per IRB, local regulations, etc.
If during the study, the investigator determines that the maternal participant is for any reason 
no longer capable of providing informed consent, the infant’s continued participation in the 
study requires consent to be obtained from the parent(s)/legal guardian as determined by 
local regulations, legal requirements, and the IRB/EC. 
Note: For the infant participant, the term parent(s)/legal guardian denotes the “legally 
authorized representative.”
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
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To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
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www.pfizer.com
Pfizer posts public disclosure synopses (clinical study report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the US Basic 
Results document is posted to www.clinicaltrials.gov.
Documents Within Marketing Authorization Packages/Submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
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The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan/contracts.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
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10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the site Source Data Agreement 
Plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study 
(or study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
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intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
For maternal immunization clinical studies conducted in pregnant women, data on the EDP
including any SAEs/nonserious AEs as well as pregnancy outcomes are collected and 
analyzed in the clinical database. All SAEs are reported to Pfizer Safety using the Vaccine 
SAE Reporting Form. In case of a new pregnancy in a maternal participant before the end of 
the study, any exposure to the investigational product is reportable to Pfizer Safety within 
24 hours of investigator awareness using the Vaccine SAE Reporting Form/EDP 
supplemental form.
The term “participant” in this section refers to (1) the maternal participant and her fetus; and 
after delivery (2) the maternal participant and (3) the infant participant.
10.2.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (eg, cesarean section, endoscopy, appendectomy): the 
condition that leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.2.2. Newly Diagnosed Chronic Medical Conditions 
An NDCMC is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
10.2.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
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c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting.  Complications that occur during hospitalization are AEs.  If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious.  When in 
doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a Pfizer 
product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited 
cases by pharmacovigilance personnel.  Such cases are also considered for reporting as 
product defects, if appropriate.
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10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording safety events on the CRF and 
for reporting safety events on the Vaccine SAE Reporting Form to Pfizer Safety.  These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and 
(3) occupational exposure. 
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE 
Reporting Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study via 
occupational exposure
Occupational exposure is 
not recorded.
Occupational exposure 
(regardless of whether 
associated with an AE)
Note:  Include all AEs/SAEs 
associated with occupational 
exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
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Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING
to describe the maximum intensity of the AE. For purposes of 
consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent
intervention indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.
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
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused the 
event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible.  This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any anonymized 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.2.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
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10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
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
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase. Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with International 
Organization for Standardization (ISO) 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.4.1. Definition of AE and ADE
AE and ADE Definition 

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational medical device.  
This definition includes events related to the investigational medical device or 
comparator for study participants, users, and other persons.  This definition also 
includes events considered related to procedures for study participants only.

An ADE is defined as an AE related to the use of an investigational medical device.  
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
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10.4.2. Definition of Serious Adverse Event, Serious Adverse Device Effect, and 
Unanticipated Serious Adverse Device Effect
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is an AE that:
a. Led to death.
b. Led to serious deterioration in the health of the participant, that either resulted 
in:

A life-threatening illness or injury.  The term “life-threatening” in the definition of 
serious refers to an event in which the participant was at risk of death at the time of 
the event. It does not refer to an event that hypothetically might have caused death, 
if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
SADE Definition

A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE.
Unanticipated Serious Adverse Device Effect (USADE) Definition

A USADE is a serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis management 
file.
10.4.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance.  Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
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10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator 
to review all documentation (eg, hospital progress notes, laboratory reports, and 
diagnostic reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information in 
the participant’s medical records, in accordance with the investigator’s normal clinical 
practice and on the appropriate form of the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of following the reporting process described in the IP 
manual.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
“severe” should not be confused with an SAE. “Severe” is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as “severe.”

An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as “severe.”
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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency and has 
provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE/SAE/Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE/SAE/ device deficiency 
as fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
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10.4.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred 
method to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.4.6. Reporting of SADEs
SADE Reporting to Pfizer Safety 
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.
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10.5. Appendix 5: Background Factors
1. Information on the following will be collected at Visit 1, Visit 4 (12-Month), and 
Visit 6 (24-Month) for all infant participants:

Educational level of parent(s) or legal guardian(s).

Exposure to smoke (including tobacco smoke).

Number of persons in the household ≥18 years of age.

Number of children <18 years of age in the household and if they attend school/ 
daycare.
o
Number of children in the household under 5 years of age (under 60 months).
o
Number of children in the household ≥5 years of age (≥60 months).
2. Information on the following will be collected at each postbirth visit:

Childcare/daycare (for infant participants).

Breastfeeding information (including whether or not breastfeeding is exclusive).
3. Information on the following will be collected at each RTI study visit:

Number of missed days of work for parent(s) or legal guardian(s) due to the infant 
participant’s illness.
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10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria Checklist 
for MA-RTI Visit – Infant Participants
When an infant MA-RTI medical visit criterion is met or confirmed, the site will obtain 
records from the medical visit and capture the healthcare information as detailed below in the 
eCRF. This information is based on respiratory-related assessments including examination 
findings, clinical findings, and any pathogen-related assessments/findings. 
Medical Visit - Visit Details and Assessment Requirements
Note: This should not be linked to a study visit but may overlap with the RTI study visit. 
The following fields and clinical assessment details should be obtained from relevant 
records for the medically attended event prior to each RTI study visit to support the 
assessment of the RTI event.

Reason for visit including date/time, eg,
o
Nasal discharge for 24 hours or more.
o
Difficulty breathing, labored breathing, or rapid breathing for any duration.
o
Cough.
o
Inability to feed for any duration due to respiratory symptoms.
o
Apnea.
o
Any other respiratory symptom of concern.

Location of medical visit (inpatient clinic, outpatient clinic, emergency department, 
urgent care, hospitalization, home visit, other). Note: study visits should NOT be 
recorded here.
o
If hospital visit, was this triggered by an RTI (include details pertaining to duration
as well as admission and discharge information and records)?

Clinical findings pertaining to respiratory symptoms and/or RTI, as detailed below but 
not limited to:
o
Presence or absence of pertinent examination findings, eg, apnea (documented as per 
chart), wheezing, fever, cough, nasal congestion, intercostal retractions, lower chest 
wall indrawing, grunting, crackles, decreased breath sounds, other abnormal breath 
sounds, dry mucous membranes, skin tenting, sunken fontanelle, difficulty feeding, 
failure to respond/unconsciousness, etc. 
o
Respiratory rate from highest/worst value of visit.
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o
Oxygen saturation (SpO2) from lowest/worst value of visit.
o
Oxygen supplementation (assisted ventilation, including type of respiratory assistance 
[respirator, “state-of-the-art” occlusive nasal prongs, face tent, etc]).

Days of supplementary oxygen.

Use of nasal cannula.

Use of high-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive).
o
Heart rate from worst value of visit when performed consistently.
o
Body weight from the date of the MA-RTI event.
o
Temperature from worst value of visit when performed consistently.
o
Additional clinical or respiratory related assessments including chest x-ray.

Local test results for RSV as part of routine clinical care:
o
Testing platform used (clinical list of all platforms and validated by research).
o
Result (list: positive, negative, indeterminate, other).

Results for any local non-RSV respiratory pathogen testing conducted as part of routine 
clinical care:
o
Result (list: detected, not detected, indeterminate)

Record the provider diagnosis, including any causative pathogen (if applicable), eg, RSV 
bronchiolitis, asthma, influenza, etc.

Obtain details of all prescribed medications including IV fluid usage.

Obtain details of all AEs/SAEs in line with study requirements. Note: MA-RTIs are not 
AEs/SAEs, unless related to the investigational product or resulting in death.
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10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
10.7.1. Informed Consent for the Maternal Participants <20 Years Old
Informed consent for maternal participants <20 years old and their infant participants will be 
obtained based on current Japanese civil code article 753 until 01 April 2022.

Married maternal participants 16 to <20 years of age are deemed to have reached 
“majority” and each maternal participant will sign the ICD for her and her infant’s study 
participation.

The maternal participants 16 years of age and unmarried maternal participants 16 to 
<20 years of age are deemed “minors.”

When the maternal participant is a minor under local law, the investigator, or a person 
designated by the investigator, will obtain written informed consent from the maternal 
participant’s legally acceptable representative, parent(s), or legal guardian as well as 
the maternal participant’s assent (affirmative agreement) for her and her child’s study 
participation before any study-specific activity is performed. The investigator will 
retain the original of each signed consent and assent document.

The assent form for a minor must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements, including applicable privacy 
laws.

The assent form for a minor used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB before use, and available for 
inspection.

The investigator must ensure that the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian is fully informed about the nature and 
objectives of the study and possible risks associated with participation.

The source documents must record that the maternal participant was a minor at 
the time of signing the ICD, how the investigator determined that the person 
signing the consent was the maternal participant’s legally acceptable 
representative, the consent signer’s relationship to the maternal participant 
(eg, parent), and that the maternal participant’s assent was obtained.

When the minor maternal participants reach the age of majority during the study, as 
recognized under local law, they must reconsent as adults to remain in the study.
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
Beginning on 01 April 2022, when the amended civil law in which individuals 18 years 
of age and older are deemed to have reached majority and marriage age for women is 
implemented:

The investigator, or a person designated by the investigator, will obtain written informed 
consent from the maternal participant 18 to <20 years of age and married maternal 
participants 16 to <18 years of age.  

For all maternal participants <16 years of age and unmarried maternal participants 16 to 
<18 years of age, the investigator, or a person designated by the investigator, will obtain 
written informed consent from the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian as well as the maternal participant’s assent.
10.7.2. Temperature Measurement and Definition of Fever

Axillary temperature will be measured at Visit 1 and as required at an unscheduled visit, 
and will be measured by the maternal participants for 7 days following vaccination.

For the maternal participants enrolled in Japan, an axillary temperature of ≥37.5°C
(99.5°F) meets the definition of a current febrile illness in the criteria for temporarily 
delaying vaccine administration described in Section 5.2.3.

For the purpose of recording the temperature in the e-diary, fever is defined as an axillary
temperature of ≥38.0°C (100.4°F) for maternal participants enrolled in Japan.
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants
As Study C3671008 is a first-in-Japanese study and in accordance with a recommendation 
from the Pharmaceuticals and Medical Devices Agency (PMDA), the study will utilize a 
sentinel cohort for the maternal participants enrolled in Japan with progression to study 
enrollment at all study sites after a safety review (data from each maternal participant 
through 14 days after vaccination).  In addition to the study procedures and requirements 
specified in the protocol for Study C3671008, the following procedures will be required for 
the maternal participants enrolled in the sentinel cohort in Japan.
10.7.3.1. Enrollment of Maternal Participants in the Sentinel Cohort
In the sentinel cohort, approximately 8 maternal participants will be enrolled.  No more than 
4 maternal participants per day can be randomized.  Vaccination of the remaining maternal 
participants in the sentinel cohort will commence no sooner than 48 hours after the fourth 
participant received her vaccination.  
10.7.3.2. Conclusion of the Sentinel Cohort
After enrollment in the sentinel cohort is completed, the Pfizer internal review committee 
(IRC) will review at least 14 days of postvaccination safety data from all maternal 
participants enrolled in the sentinel cohort, including all local reactions, systemic events, and 
AEs.  An acceptable review will trigger an expansion of study enrollment to all study sites in 
Japan. Refer to the IRC charter for further details.
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10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or Telephone; 14 to 16 Days 
After Vaccination)
All maternal and infant participants enrolled in this study will follow the protocol for 
Study C3671008.  In addition, the maternal participants enrolled in the sentinel cohort in 
Japan will have a Day 15 follow-up visit conducted either at the study site or via telephone.  
This visit should be conducted 14 to 16 days after vaccination. 

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given since the last visit.

Review the participant’s e-diary data.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6.

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit.
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10.7.3.4. Schedule of Activities for Maternal Participants Enrolled in the Sentinel 
Cohort in Japan
The following table provides an overview of the protocol visits and procedures for the 
maternal participants enrolled in the sentinel cohort in Japan.  Refer to Section 1.2.3.1 for the 
Schedule of Activities for the Maternal Participants: RTI Surveillance for Medically 
Attended Respiratory Tract Illness Visits (Vaccination Until the End-of-Study Visit).
Visit Description
Screening 
and 
Vaccinationa
Day 15 
Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month 
Postdelivery
Visit Window (Days)
28 Days Prior 
to 
Vaccination 
to Day 1
14 to 16 Days
After 
Vaccination
28 to 42 Days
After 
Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity 
Unit
Clinic, Home, or 
Telephone
Informed consent for maternal 
participant and her infant
X
Assign single maternal participant 
identifier 
X
Demography
X
Medical history including obstetric 
historyd
X
Record current/former alcohol, 
tobacco, marijuana, or any illicit drug 
usage
X
Record vital signs
X
Targeted physical and obstetric 
examination performed on the same 
day or within 7 days before the 
vaccination visit
X
Record details of any antenatal and/or 
postnatal steroid treatment, 
monoclonal antibodies, blood 
products, or Rho(D) immune globulin
X
X
X
X
X
Record details of the maternal 
participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
X
Review eligibility criteria
X
X
X
X
Review temporary delay criteria
X
Prevaccination blood draw for 
serologic assessment (~15 mL) on the 
same day or within 7 days before the 
vaccination visit
Xe
Assign randomization and container 
number
X
E-diary training, dispense digital 
thermometer and measuring devicef
X
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Visit Description
Screening 
and 
Vaccinationa
Day 15 
Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month 
Postdelivery
Visit Window (Days)
28 Days Prior 
to 
Vaccination 
to Day 1
14 to 16 Days
After 
Vaccination
28 to 42 Days
After 
Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity 
Unit
Clinic, Home, or 
Telephone
Obtain and record baseline 
assessment of prespecified systemic 
events on the day of and prior to 
vaccination in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 
30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic 
assessment 
(~15 mL)
Xe
Record pregnancy outcome 
information
X
Review e-diary datag
X
X
Record AEs, as appropriateh
X---------------------------------------------X
Record SAEs, as appropriateh
X
X
X
X
X
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Visit Description
Screening 
and 
Vaccinationa
Day 15 
Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month 
Postdelivery
Visit Window (Days)
28 Days Prior 
to 
Vaccination 
to Day 1
14 to 16 Days
After 
Vaccination
28 to 42 Days
After 
Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity 
Unit
Clinic, Home, or 
Telephone
Record details pertaining to MA-RTI 
visiti
Assessment of confirmed MA-RTI events during the study as detailed in 
Section 1.2.3.1 of the schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = 
intrapartum antibiotic prophylaxis; ICD = informed consent document; MA-RTI = medically attended 
respiratory tract illness.
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization 
assessments and test results to confirm maternal participant eligibility for this clinical trial can be obtained a
reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation 
and collection of AEs and SAEs through 28 days after vaccination must occur even if delivery occurs 
within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge 
following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal 
standard of care, perform an ultrasound examination. As part of the obstetric history, details regarding the 
last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported 
in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital 
thermometer for recording daily temperatures, and will be provided with instructions on their use. 
Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) 
a baseline assessment of prespecified systemic events on the day of and prior to vaccination and 
reactogenicity events from Day 1 to Day 7 following vaccination (where Day 1 is the day of vaccination).  
Remind maternal participants that the study staff/field worker may contact them to obtain additional 
information on events entered into the e-diary.  Ask maternal participants to contact the investigator or 
site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 following vaccination, to 
determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal 
participant may be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to 
evaluate maternal participant compliance and as part of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 
28 days after vaccination.  From the signing of the ICD until the maternal participant completes the study, 
all SAEs will be collected.  Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the 
schedule of assessments in Section 1.2.3.1. These events will not be captured as safety events, unless the 
investigator or an appropriate designee deems them to be related to the investigational product or to have 
resulted in death.
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10.7.4. Exclusion Criterion 12 Clarification
For exclusion criterion 12, “Current alcohol abuse or illicit drug use. Note: Marijuana use is 
not considered an exclusion criterion for the study when elicited in participant screening, 
though it may be considered illicit in some locales.” In Section 5.2.1, any current use of an 
illicit drug including marijuana will not be permitted for maternal participants enrolling from 
study sites in Japan.
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and Unanticipated SAE
Caused by Medical Device
Definition of SAE caused by medical device:
An SAE caused by medical device is defined as an AE caused by a medical device which led 
to an outcome characteristic to SAEs, or a device-related incident whose recurrence might 
lead to death or serious deterioration in health.
NOTE: See the Medical Device Adverse Events, Adverse Device Effects, Serious Adverse 
Events, and Device Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting section (Appendix 4). Deficiencies fulfilling the definition of an 
AE/SAE will also follow the processes outlined in Section 8.3.3 and Appendix 2 of the 
protocol.
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix – Applicable 
to the Philippines, Gambia, and South Africa Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Participants who have not had ultrasound assessments to determine eligibility during 
routine care should be consented, and have an ultrasound within 90 days prior to 
vaccination in order to comply with inclusion criteria #1 in Section 5.1.1.
Safety endpoints:
The time period and frequency for collecting AE and SAE information by the investigator 
and site staff should follow Appendix 2, with the exception of the additional screening 
window for sites conducting ultrasounds procedures from -90 to -28 days. At these sites, the 
safety reporting periods should be as follows:

AEs occurring up to 48 hours after ultrasound assessment that the investigator 
deems are related to the study procedure must be reported in the CRF.

The active collection period for SAEs begins once informed consent has been 
provided until the maternal participant completes the study.

The active collection period for nonserious AEs begins 28 days prior to 
vaccination and continues through a minimum of 28 calendar days after
vaccination as described in Section 8.3.1 and Section 10.2.
MA-RTI endpoints:
Maternal MA-RTIs are collected from the time of vaccination to the end of the study period 
as described in Section 8.1.2.
Note: For maternal participants who are screen failures, the active collection period ends 
when screen failure status is determined. 
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10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to South 
Korea and Taiwan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Section 5.1.1: Inclusion criterion 1 states that healthy women ≤49 years of age who are 
between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an 
uncomplicated, singleton pregnancy, who are at no known increased risk for complications 
are eligible for the study.
Please find below country-specific minimum age requirements for study entry into the 
protocol:

In South Korea, the minimum age requirement of maternal participants who can be 
enrolled into the study is ≥19 years of age.

In Taiwan, the minimum age requirement of maternal participants who can be 
enrolled into the study is ≥20 years of age.
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10.10. Appendix 10: Country-Specific Appendix – Applicable to South Korea Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Exclusion Criterion 12 Clarification
For exclusion criterion 12, “Current alcohol abuse or illicit drug use.  Note: Marijuana use is 
not considered an exclusion criterion for the study when elicited in participant screening, 
though it may be considered illicit in some locales.”  In Section 5.2.1, any current use of an 
illicit drug, including marijuana, will not be permitted for maternal participants enrolling 
from study sites in South Korea.
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10.11. Appendix 11: Country-Specific Appendix – Applicable to the Philippines Only
The following supplementary text should be read in conjunction with the C3671008 protocol
Section 10.1, Appendix 1 requirements, which details the Regulatory, Ethical, and Study 
Oversight Considerations, including the compensation/reimbursement requirements for study 
participants.
Study participants enrolled in the Philippines may be compensated to cover expenses related 
to completion of maternal and infant study visits in accordance with country-specific
applicable laws and regulations, as approved by the IRB/EC. In addition, compensation may 
be provided upon e-diary completion with the approval of the IRB/EC.
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10.12. Appendix 12: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ADE
adverse device effect
AESI
adverse event of special interest
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
Apgar
appearance, pulse, grimace, activity, and respiration
AST
aspartate aminotransferase
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
Clinical Laboratory Improvement Amendments
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EAC
endpoint adjudication committee
EACC
endpoint adjudication committee charter
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine 
GA
gestational age
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Abbreviation
Term
GBS
group B streptococcal
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBIG
hepatitis B immune globulin
HBV
hepatitis B virus
HCP
healthcare provider
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IAP
intrapartum antibiotic prophylaxis
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
Ig
immunoglobulin
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ISF
investigator site file
ISO
International Organization for Standardization
IUI
intrauterine insemination
IV
intravenous
IWR
interactive Web-based response
LFT
liver function test
LMIC
lower- and middle-income country
LMP
last menstrual period
LRTI
lower respiratory tract illness
MA-LRTI
medically attended lower respiratory tract illness
MA-RTI
medically attended respiratory tract illness
MCAR
missing completely at random
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NAAT
nucleic acid amplification technology
NDCMC
newly diagnosed chronic medical condition
PCD
primary completion date
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Abbreviation
Term
PCR
polymerase chain reaction
PFS
prefilled syringe
PMDA
Pharmaceuticals and Medical Devices Agency
PT
prothrombin time
RAD
reactive airway disease
RCDC
reverse cumulative distribution curve
RSV
respiratory syncytial virus
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RTI
respiratory tract illness
RT-PCR
reverse transcription–polymerase chain reaction
SAE
serious adverse event
SADE
serious adverse device effect
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2 
SMS
short message service
SoA
schedule of activities
SOP
standard operating procedure 
SpO2
oxygen saturation
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Tdap
tetanus, diphtheria, and acellular pertussis vaccine
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VE
vaccine efficacy
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11. REFERENCES
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Straňák Z, Saliba E, Kosma P, et al. (2016) Predictors of RSV LRTI Hospitalization in 
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Gilbert W, Jandial D, Field N, et al. Birth outcomes in teenage pregnancies. J Matern 
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McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer 
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Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants 
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Graham BS. Biological challenges and technological opportunities for respiratory 
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Madhi SA, Polack FP, Piedra PA, et al. Respiratory syncytial virus vaccination during 
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34
Regen AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization 
during pregnancy in 4 high-income countries, 2010–2016.  Clin Infect Dis 
2018;67(12):1915-8. Available from: https://doi.org/10.1093/cid/ciy439. Accessed: 
25 Nov 2019.
35
Pettker CM, Goldberg JD, El-Sayed YY, et al. Committee opinion number 700: methods 
for estimating the due date. Obstet Gynecol 2017;129(5):e150-54.
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European Commission. Ethical considerations for clinical trials on medicinal products
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10/2017_09_18_ethical_consid_ct_with_minors.pdf. Accessed 21 Feb 2019.
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38
Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: case definition & guidelines for 
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2016;34(49):6047-56.
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Protocol Amendment 4, 22 March 2021
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
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A PHASE 3, RANDOMIZED, DOUBLE-BLINDED,
PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND 
SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F 
SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING 
PREGNANCY
Investigational Product Number:
PF-06928316 
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine 
United States (US) Investigational New 
Drug (IND) Number:
017931
European Clinical Trials Database 
(EudraCT) Number:
2019-002943-85
Protocol Number:
C3671008
Phase:
3
Short Title: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants 
Born to Women Vaccinated During Pregnancy.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original 
protocol
05 December 2019
Not applicable (N/A)
Protocol 
Amendment 1
24 March 2020
PROTOCOL SUMMARY: Clarification text was 
added in various sections of the main body of the 
protocol to match the revisions made to the protocol 
summary.
Throughout: The protocol now contains final 
wording regarding the double-blinded, placebo-
controlled study design and the final dose and 
formulation of the respiratory syncytial virus 
stabilized prefusion F subunit vaccine (RSVpreF). 
This is as a result of the analysis of the safety, 
tolerability, and immunogenicity data from the 
C3671003 maternal Phase 2b trial.
Section 1.2.1 Study Design – Maternal Participants: 
The final dose and formulation of RSVpreF were 
inserted, including the lyophile match for the 
placebo.
Section 1.2.2 Study Design – Infant Participants: The 
text box pertaining to the vaccine group arms was 
deleted. The maternal-infant dyads will be randomly 
assigned in this study. Rationale: Infant participants 
will not be administered the investigational product. 
Therefore, the current placement is potentially 
confusing to readers. 
Section 1.2.3 Schedule of Activities for Maternal 
Participants, Section 5.2.3, and Section 8.10.1: 
Clarification text was added as follows:
o
The immunogenicity blood collection and 
physical examination window requirements 
before vaccination were aligned to provide 
greater logistical convenience for the 
investigational sites with respect to enrolling 
participants into the study.
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CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
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Document History
Document
Version Date
Summary of Changes and Rationale
o
The wording for the study objectives pertaining 
to the request for intrapartum antibiotic 
prophylaxis (IAP) details for maternal 
participants with a group B streptococcal (GBS) 
status was revised to be consistent with the study 
procedural objectives, which are to collect GBS 
status and to ascertain whether any medication 
was given for IAP. This resulted in the deletion 
of the text in Section 6.5.3, as this information is 
captured in Section 8.10.3.
o
A reference to the immunogenicity blood draws 
for maternal participants was added to clarify the 
adverse event (AE) reporting requirements for 
events that might occur as a result of study-
related procedures.
Section 1.2.3.1 Schedule of Activities for Maternal 
Participants – Respiratory Tract Illness (RTI) 
Surveillance for Medically Attended Respiratory 
Tract Illness (MA-RTI) Visits: 
o
Details to be collected during an MA-RTI were 
revised.
o
Clarification was added regarding the safety 
reporting requirements for MA-RTI events that 
might occur during the study. 
Section 1.2.4 Schedule of Activities for Infant 
Participants: 
o
Visit flexibility was increased to prioritize 
participant safety and adherence to local 
guidance in the event of a coronavirus disease 
2019 (COVID-19) outbreak or other outbreaks. 
o
The physical examination and vital sign 
assessment windows for the study were aligned 
to provide greater logistical convenience for the 
investigational sites with respect to compliance to 
study protocol requirements.  
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Document History
Document
Version Date
Summary of Changes and Rationale
o
The protocol safety reporting criteria and period 
for adverse events (AEs), serious adverse events 
(SAEs), and newly diagnosed chronic medical 
conditions (NDCMCs) were streamlined.
Section 1.2.4.1 Schedule of Activities for Infant 
Participants: RTI Study Visits During the Study: The 
table was revised, including splitting the schedules of 
activities for unscheduled RTI visits for all infant 
participants into RTI surveillance from birth to 6 
months and RTI surveillance from 6 months to the 
end of the study. The procedures were streamlined 
for these RTI study visits to improve clarity and 
consistency.
Table 1: Clarification has been added as to when a 
study visit is triggered for reported MA-RTI endpoint 
events on the study. Day 1 is the day of the MA-RTI 
visit as detailed in Section 8.11.7.
In addition, clarification has been added as to what 
constitutes the site source for confirmed study 
endpoint criteria, in order to provide the sites 
guidance on what documentation will eventually be 
submitted to the endpoint adjudication committee 
(EAC) for evaluation.
Section 3.1: The exploratory endpoints were revised 
to correspond with the planned statistical analyses of 
RTI events in the pediatric population. This does not 
represent a change to the study design but instead 
better reflects the total statistical analysis plan. 
Section 3.1, Section 3.2, and throughout: To improve 
clarity and ensure consistency, the use of “RSV-
neutralizing antibody titers” has been changed to 
RSV serum neutralizing titers.” This is the sponsor’s 
preference based on what the neutralizing activity 
assay is based upon, and in this case, it is whole 
serum and not just the purified antibodies during 
these immunogenicity assessments.
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CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
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Document History
Document
Version Date
Summary of Changes and Rationale
Section 3.3, Section 8.1.1.2, Section 8.1.3, and 
Section 10.2: For further clarification, the protocol’s 
safety and endpoint reporting requirements were 
amended to ensure consistency with Pfizer’s updated 
safety reporting requirements for endpoint-defined 
studies.
Section 4.3: The text “availability of these data are 
expected in 2020” was removed as this statement 
does not accurately reflect the current decision-
making process for the dose and formulation 
selection activities for this study. 
Section 5.2.1: Clarification text was added to the 
exclusion criterion for body mass index (BMI) and 
congenital anomalies based on study requirements.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: The 
tetanus, diphtheria, and acellular pertussis vaccine 
(Tdap) administration requirements text was 
modified to describe the timing of vaccinations based 
on data from the C3671004 study, once available. 
This change will better reflect clinical practice and 
will facilitate recruitment of suitable maternal 
participants for the study.
Section 6.1.1, Section 6.1.3, Section 8.4, and Section 
8.10.1: Clarification text was added to address 
investigational product reconstitution volume and 
administration requirements. This change is to ensure 
consistency with the investigational product 
administration documentation for the study.  
Section 7.2: Clarification text was added to address 
the notification process for biological sample 
management in the event of study participant 
withdrawal from the study.
Section 7.3 and Appendix 1 Informed Consent 
Process: Clarification text was added to address 
study retention and data collection requirements for 
the study. In addition, further clarification has been 
added to emphasize the informed consent process 
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Protocol Amendment 4, 22 March 2021
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
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Document
Version Date
Summary of Changes and Rationale
during circumstances where the maternal participant 
is no longer able to provide consent but the infant 
participant’s continued participation in the study 
could be retained by the parent(s)/legal guardian as 
per local regulatory, local laws, and local governance 
approval.
Section 8.1.1.1: Clarification text was added to 
provide guidance regarding the midturbinate swab 
processing requirements and the definition of 
acceptable certified/accredited laboratory bodies for 
this process in the study.
Section 8.2.1.1 and Section 8.10.1: The reporting 
requirements for Grade 4 local reactions in the study 
were clarified; the assessment and reporting are 
carried out by the investigators (or appropriately 
qualified designees).
Section 8.3.1.1, Section 8.3.1.2, Section 8.3.5.1, 
Section 8.3.5.2, Section 8.10, and Section 8.11: The 
reporting requirements were clarified for this 
vulnerable patient population with regard to AEs and 
SAEs likely to occur in the study in women with 
gestational age (GA) eligibility criterion between 24 
0/7 and 36 0/7 weeks.
Section 8.3.6: Text was added to address and 
standardize reporting procedures for adverse events 
of special interest (AESIs) for this patient population.
Section 8.3.7 and Appendix 4: Several Pfizer text 
revisions were incorporated regarding device 
deficiencies and the safety reporting requirements for 
this study.
Section 8.10: The immunogenicity blood collection 
and physical examination window requirements 
before vaccination were aligned to provide greater 
logistical convenience for the investigational sites 
with respect to enrolling participants into the study.  
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Section 8.10.1: The prepregnancy BMI text revisions 
in Section 5.2.1 were aligned with the study
assessment requirements for maternal participants at 
screening.
Section 8.10.2, Section 8.10.3, Section 8.10.4, and 
Section 8.10.6: Clarification text was added to the 
MA-RTI reporting requirements for maternal 
participants in the study to provide guidance and 
ensure the investigational sites provide accurate 
information pertaining to these self-reported events.
Section 8.11.1 to Section 8.11.6: Clarification text 
was added (where applicable) to address the 
following study assessments:
o
“Birth weight must be the first birth weight and 
cannot be based on the standard-of-care 
examination” was removed as this statement is 
confusing to the investigational sites. Birth 
weight assessments have now been realigned 
with standard-of-care assessments at the study 
visit to aid compliance with study assessments 
and requirements.
o
Clarification text was added regarding the 
reporting of standard-of-care measurements for 
vital sign assessments. 
o
In addition, the physical examination and vital 
sign assessment windows for the study were 
aligned to provide greater logistical convenience 
for the investigational sites to comply with study 
protocol requirements.  
o
For further clarification, the RTI study visit 
assessment requirements were amended to 
emphasize the difference between the MA-RTI 
visit criteria and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements. 
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CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
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Version Date
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Section 8.11.7.1: For further clarification, the RTI 
study visit assessment requirements have been 
amended to emphasize the following:
o
The RTI study visit window, including nasal 
swab collection from the MA-RTI notification 
for the infant participant.
o
Duplicate text was removed pertaining to the 
MA-RTI definition and the signs and symptoms 
of interest pertinent to an RTI study visit. 
o
Guidance regarding the difference between the 
MA-RTI visit and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements.
Section 8.11.8: Clarification text was added to 
address the RTI study visit window, including nasal 
swab collection from the MA-RTI notification for the 
infant participant.
o
For further clarification, the RTI study visit 
assessment requirements have been amended to 
emphasize the difference between the MA-RTI 
visit and the subsequent study visit after the event 
has been reported. This is to improve clarity and 
consistency with the RTI study visit requirements 
and provide guidance to the investigational sites.
Section 9.1.2.1, Section 9.1.2.2, Section 9.4.1, 
Section 9.2, and Section 9.5: Text was added to 
clarify the statistical analysis procedures in line with 
the current revisions.
Appendix 2: Clarification text was added to support 
the safety and pregnancy outcome reporting 
requirements for participants who may experience 
exposure during pregnancy while in the study.
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CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 9
Document History
Document
Version Date
Summary of Changes and Rationale
Appendix 5: Further clarification was added to the 
background factors of interest during the infant’s 
participation in the study. 
Appendix 6: Clarification text was added to the 
examination and treatment criteria checklist for 
reported MA-RTI visits.  This is to ensure there is 
some consistency to the source records provided for 
these events in relation to the protocol requirements.
Throughout: Several changes were made to 
incorporate the replacement of the Clinical Trial 
Serious Adverse Event Report Form (CT SAE 
Report Form) to Vaccine SAE Reporting Form, as 
part of the new vaccine SAE reporting requirements 
for Pfizer. 
Throughout: Minor editorial revisions were 
incorporated as appropriate. 
Protocol 
Amendment 2
26 June 2020
Section 5.1.1: Administrative update was 
incorporated to address the recently added 
Appendices 7 and 8.
Appendix 7: A country-specific appendix was added 
for Japan to address consent/assent issues for minors, 
temperature measurement, definition of fever, and 
enrollment of maternal participants in the sentinel 
cohort for safety monitoring.
Appendix 8: A country-specific appendix was added 
for the Gambia and South Africa to address an 
extension to the screening period for maternal 
participants with regard to GA requirements and 
consent process.
Protocol 
Amendment 3
26 August 2020
PROTOCOL SUMMARY: Added clarification text 
to the exploratory endpoint section for the infant 
participants; changes were made in the protocol 
summary to match the revisions made in the main 
body of the protocol.
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Version Date
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Section 1.2.2: Study Design – Infant Participants: 
Added text to address RSV seasonality and the 
required RTI surveillance periods during the study. 
Rationale: The previous placement was potentially 
confusing to readers. The revisions provide clarity to 
the investigational sites with regard to the RTI 
surveillance follow-up activities.
Section 1.2.3 and Section 1.2.3.1: Added clarification 
text (where applicable) to address the following: 
o
Added “Home or Telephone” to the type of visit 
options allowed for the 6-month-postdelivery 
visit.
o
Added clarification text to the alcohol history 
reporting requirements and included “obstetric” 
in the screening assessment requirements for the 
study.
o
Added “study staff,” as study personnel are 
allowed to collect and report baseline and 
reactogenicity assessments reported during the 
evaluation period.
o
Added clarification text regarding the reporting 
requirements for AEs, SAEs, and MA-RTIs for 
maternal participants.
Section 1.2.4 - Schedule of Activities for Infant 
Participants: 
o
Added “Home” to the type of visit options 
allowed for the 1-month and 6-month follow-up 
visits and added further clarification to the visit 
status during potential COVID-19 pandemic 
situations or other natural disasters. Rationale: 
Infant participant visit options were aligned with 
the maternal participant requirements to allow for 
visit flexibility.
o
For further clarification, the physical examination 
and vital sign assessment expectations at birth 
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and at the 1-month visit were aligned to provide 
greater logistical convenience for the 
investigational sites to comply with study 
protocol requirements.
Sections 1.2.4, 1.2.4.1, 8.1.1, and 8.11 to 8.12:
Added clarification text (where applicable).
o
To address alternate nasal swab collection 
procedures, if needed, during potential 
COVID-19 pandemic situations or other natural 
disasters.
o
Clarification text was added with regards to the 
start of the reporting period for MA-RTI events 
upon the infant’s delivery.  This is to improve 
clarity and consistency with the capturing and 
reporting requirements for MA-RTI events and 
provide guidance to the investigational sites.
Sections 1.2.4.1, 8.11.7.1, 8.11.8, and Appendix 6: 
o
Added temperature and body weight 
measurements for infant participants during study 
RTI visits.
o
For vital sign measurements, especially oxygen 
saturation measurements (where applicable), 
clarification text was added to state that it is 
recommended that the participant not be 
receiving supplemental oxygen at the time of 
measurement.
These updates are to ensure consistency with the 
study RTI assessment visits after a confirmed 
MA-RTI event.
Section 3.1: Added clarification text as follows:
o
Table 1.
Primary and Secondary Endpoint 
Events and Definitions in Infant Participants: For 
further clarification, added descriptive text to the 
table header to address endpoint events listed 
within the table. In addition, made corrections to 
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Protocol Amendment 4, 22 March 2021
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CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
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the overlapping respiratory rate measurements 
provided for some study endpoint events. These 
changes were made to improve clarity and 
consistency with the endpoint reporting and 
evaluation process for the study.
o
For the infant participant exploratory objectives,
added the planned statistical analysis period of
“after 6 months of age” to “all-cause MA-RTIs 
and hospitalizations due to RSV” in the pediatric 
population based on regulatory authority 
feedback from South Korea.
o
Incorporated revisions to align endpoints with 
study duration, specifically MA-LRTIs due to 
RSV A and RSV B, and MA-RTIs associated 
with non-RSV respiratory pathogens.
o
Added clarification text to address the analysis 
plans for the healthcare utilization endpoints.
Section 4.1: For further clarification, added text to 
address the desire to enroll across gestational age.
Section 4.3: Added a brief summary of the safety and 
immunogenicity results from the C3671003 trial to 
support the decision-making process for this study.
Section 5.1.1: Inserted administrative 
update/clarification text with regards to:
o
Participant eligibility guidance documentation 
available within the investigator site file.
o
The informed consent process for maternal 
participants.
Section 5.2.1: Based on study requirements:

Added clarification text to exclusion criterion 7, 
which addresses the investigator’s judgment 
when assessing participant eligibility (maternal 
participant or her fetus) and regional endemic 
conditions during routine maternal care, as per 
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local standards of care and obstetric 
recommendations.

Added clarification text to address illicit drug use 
pertaining to marijuana.
Section 5.2.2: Deleted the infant participants 
exclusionary criterion pertaining to the “receipt of 
investigational or approved monoclonal antibodies 
against RSV.”  This was to provide additional 
clarification to the investigational sites with regards 
to the infant’s eligibility criteria.
Sections 5.2.3, 6.5.1, and 6.5.2: Modified the Tdap 
administration requirements text to describe the 
timing of vaccinations based on recent data from the 
C3671004 study (A Phase 2b, Placebo-Controlled, 
Randomized, Observer-Blind Study to Evaluate the 
Safety, Tolerability, and Immunogenicity of a 
Respiratory Syncytial Virus (RSV) Vaccine When 
Administered Concomitantly With Tetanus, 
Diphtheria, and Acellular Pertussis Vaccine (Tdap) 
in Healthy Nonpregnant Women 18 Through 49 
Years of Age; ClinicalTrials.gov identifier: 
NCT04071158).
Section 6.1.4: Added text to clarify what constitutes 
a medical device with regards to the investigational 
product in this study.
Section 6.5.2: Added text to clarify the tetanus and 
diphtheria vaccine administration requirements 
during the study.
Section 6.5.4: For further clarification, added text to 
address prohibited vaccinations and treatments for 
infant participants.  This is to provide guidance to the 
investigational sites.
Section 6.5.5: Added text to clarify the permitted 
treatments, vaccines, and procedures acceptable to 
infant participants enrolled in the study.
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Sections 8.2.1 to 8.2.1.2 and Section 8.10.1: For 
further clarification, amended the e-diary completion 
requirements to emphasize the different reporting 
and/recording options for reactogenicity events 
should illiterate maternal participants be enrolled in 
the study. This is to improve clarity and consistency 
with the reactogenicity reporting requirements at the 
investigational sites.
Table 6 and Section 8.2.1.3: Based on regulatory 
feedback, provided a description of the intensity 
scale for the reactogenicity event “fever.”
Sections 8.3.1 to 8.3.1.2, Sections 8.3.5.2 to 8.3.8.1, 
and Section 10.2.3: Added clarification text (where 
applicable) to address the following safety-related 
updates and provide guidance to the investigational 
sites:
o
Several Pfizer text revisions were incorporated 
regarding the safety reporting requirements for 
this study.
o
Text was added to clarify the SAE reporting 
timelines for the study and provide guidance 
regarding the evaluation of and assessment 
procedures for congenital anomalies.
Section 8.10.1: For further clarification, aligned the 
study assessment window requirements before 
vaccination to provide guidance and greater logistical 
convenience for the investigational sites with respect 
to enrolling participants into the study.
Section 8.10.3: Added clarification text with regards 
to the reporting requirements for maternal 
participants diagnosed as GBS positive and 
pregnancy outcome information. This is to improve 
clarity and consistency with the reporting 
requirements at investigational sites.
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Section 8.11.1: Added clarification text on how the 
infant participant’s identifier will be assigned for this 
study.
Sections 8.11.1 to 8.11.6: Added clarification 
regarding the reporting of standard-of-care 
measurements for vital sign assessments, 
measurements, and physical examination procedures
(where applicable) to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 9.2 and Section 9.4.1: Modified text to more 
generally describe Type 1 error control procedures 
and refer to the statistical analysis plan (SAP) for 
details.
Section 9.4.3.2: Added clarification regarding the 
planned analyses for the healthcare utilization 
endpoints.
Section 10.2.5: Deleted the “SAE Reporting to Pfizer 
Safety via an Electronic Data Collection Tool” 
section. For consistency, only the Vaccine SAE 
Reporting Form process will be used.
Appendix 6: Added clarification text to the 
microbiological data collection requirements for the 
study based on any pathogen-related 
assessments/findings performed as part of the 
participants routine clinical care. This is to ensure 
there is some consistency to the source records 
provided for these events in relation to the protocol 
requirements and to address regulatory guidance in 
light of the COVID-19 outbreak or other outbreaks.
Appendix 7: Added clarification text to the 
following:
o
Incorporated minor editorial revisions into the 
Schedule of Activities for Maternal Participants 
Enrolled in the Sentinel Cohort in Japan.
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o
Added clarification text to exclusion criterion 12 
regarding the definition of illicit drug use based 
on country-specific requirements.
o
Incorporated clarification text regarding the 
definition of an SAE caused by a medical device.
Appendix 9: Added a country-specific appendix for 
South Korea and Taiwan to address the minimum 
age requirements for maternal participants in each 
country.
Throughout: Incorporated minor editorial revisions 
as appropriate.
Protocol 
Amendment 4
22 March 2021
PROTOCOL SUMMARY: Changes were made in 
the protocol summary to match the revisions made in 
the main body of the protocol.   
Section 1.2.3: Added text to address safety reporting 
requirements during consent/assent for minors 
enrolled as maternal participants in the study. 
Section 2.1: Added text to address the enrollment of 
adolescent menarchal females into the study, ie, no 
lower age limit for maternal participants. This is 
based on recent regulatory feedback regarding the 
study design for RSVpreF evaluation in pregnant 
adolescent females.
Section 3.1 and Section 9.4.1: The secondary and 
exploratory endpoints were revised to correspond 
with the planned statistical analyses of RTI events in 
the pediatric population:
o
Updated secondary objectives pertaining to 
hospitalization and MA-LRTI due to any cause, 
extended the efficacy analysis to be in line with 
the duration of follow-up for infant participants 
during the first year of their participation in the 
study, which is 360 days after birth. 
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o
An additional secondary objective added to 
assess the efficacy of RSVpreF in reducing the 
incidence of MA-LRTI due to RSV.
o
An additional exploratory objective added to 
assess the efficacy of RSVpreF in reducing the 
incidence of MA-RTI, MA-LRTI, and severe 
MA-LRTI in premature infants <37 weeks of 
age. 
These updates are reflected in the statistical section 
of the protocol and do not represent a change to the 
study design but instead better reflect the total 
statistical analysis plan.
Section 4.1: For further clarification, added text to 
address the consent/assent requirements for minors 
enrolled as maternal participants in the study.
Section 4.1 and Section 4.1.2: Given the COVID-19 
pandemic situation, and the variable RSV season, the 
maternal participant sample size on the study may 
need to be increased and enrollment could possibly 
go up to 10,000 maternal participants.
Section 4.4: Added text to clarify the study definition 
for a completed maternal/infant participant in the 
study. 
Section 5.1.1: Added clarification with regards to
inclusion criteria and incorporated administrative 
update:
o
Removed the lower age limit for healthy pregnant 
females likely to be eligible for enrollment in the 
study. This change will facilitate recruitment of 
suitable maternal participants for the study.
o
Allowed the GA determination to be based upon 
the first trimester ultrasound examination alone, 
without the last menstrual period, in countries 
where this is routine. This is to improve clarity 
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Summary of Changes and Rationale
and consistency with the GA determination 
requirements at the investigational sites. 
o
Updated criterion 4 regarding fetal anomaly 
ultrasound examination requirements in the 
study. This is to improve clarity and ensure 
consistency with study requirements at 
investigational sites.
Section 5.2.1: Incorporated administrative update and
clarification with regards to:
o
Marijuana use and maternal participant 
eligibility in the study. 
o
The use of licensed COVID-19 vaccines or 
COVID-19 vaccines authorized for temporary 
or emergency use based on regulatory and 
national recommendations in maternal 
participants enrolled into the study.
This was to provide additional clarification to the 
investigational sites with regards to the eligibility 
criteria of maternal participants.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: Due 
to the current COVID-19 pandemic, added text to 
clarify the vaccination delay criteria and nonvaccine 
administration window for maternal participants 
receiving licensed COVID-19 vaccines or 
COVID-19 vaccines authorized for temporary or 
emergency use. This change is consistent with other 
nonstudy vaccines allowed in the study. 
Section 6.3.1, Section 8.1.2, Section 8.2.1 to 
Section 8.2.1.3, Section 8.3, Section 8.3.1, 
Section 8.3.1.2, Section 8.10.1 to Section 8.10.6, and 
Section 10.1.3: Added text to clarify the 
consent/assent requirements during study 
procedures/assessments in the event “a minor” is 
enrolled as a maternal participant. This is to improve 
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clarity and ensure consistency for the investigational 
sites to comply with study protocol requirements.
Section 8.3.8.1: Added text to make the following 
safety-related updates and provide guidance to the 
investigational sites:
o
Incorporated safety reporting text for participants 
who report a positive test result for severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-
2) during the study.
o
Text was added to clarify the AESI reporting 
requirements for the study and provide guidance 
regarding the definition of and categorization of a 
developmental delay in infant participants. 
Section 8.10.1: Incorporated administrative update 
regarding which body systems are deemed 
mandatory and which discretionary during physical 
examination procedures for maternal participants in 
the study. This is to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 8.11.1: Incorporated text regarding the 
reporting of standard-of-care measurements for vital 
sign and physical examination procedures at the 
infant’s birth. This is to provide greater logistical 
convenience for the investigational sites to comply 
with study protocol requirements.
Section 8.11.7, Section 8.11.8, and Section 8.12: 
Added text to clarify the nasal swab collection 
requirements from infant participants during a 
confirmed MA-RTI episode.  This is to provide 
flexibility and prioritize participant safety during the 
study.
Section 9.3, Section 9.4.2, Section 9.4.3, and 
Section 9.4.3.2: Added text to clarify the statistical 
analysis procedures in line with the current revisions.
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Version Date
Summary of Changes and Rationale
Appendix 7 and Appendix 9: Removed the lower age 
limit for healthy pregnant females likely to be 
eligible for enrollment into the study. In addition, 
incorporated minor editorial revisions to the 
informed consent document for maternal participants 
enrolled in Japan only. 
Appendix 8: Added the Philippines to the list of 
countries impacted by an extension to the screening 
period for maternal participants with regard to GA 
requirements and consent process.
Throughout: Incorporated minor editorial revisions 
as appropriate.
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................28
1. PROTOCOL SUMMARY...................................................................................................29
1.1. Synopsis ..................................................................................................................29
1.2. Schematic for Study Participants ............................................................................38
1.2.1. Study Design – Maternal Participants ........................................................38
1.2.2. Study Design – Infant Participants .............................................................39
1.2.3. Schedule of Activities for Maternal Participants........................................40
1.2.3.1. Schedule of Activities for Maternal Participants: RTI 
Surveillance for Medically Attended Respiratory Tract Illness 
Visits (Vaccination Until the End-of-Study Visit) ............................43
1.2.4. Schedule of Activities for Infant Participants.............................................44
1.2.4.1. Schedule of Activities for Infant Participants: Respiratory 
Tract Illness Study Visits During the Study......................................46
2. INTRODUCTION ...............................................................................................................49
2.1. Study Rationale .......................................................................................................50
2.2. Background .............................................................................................................50
2.3. Benefit/Risk Assessment.........................................................................................51
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................52
3.1. Infant Participants ...................................................................................................52
3.2. Maternal Participants...............................................................................................58
3.3. Protocol-Defined Efficacy Endpoints .....................................................................59
4. STUDY DESIGN.................................................................................................................59
4.1. Overall Design.........................................................................................................59
4.1.1. Approximate Duration of Participation for Each Participant .....................61
4.1.2. Approximate Number of Participants.........................................................61
4.2. Scientific Rationale for Study Design.....................................................................61
4.3. Justification for Dose ..............................................................................................61
4.4. End of Study Definition ..........................................................................................63
5. STUDY POPULATION......................................................................................................63
5.1. Inclusion Criteria.....................................................................................................63
5.1.1. Inclusion Criteria – Maternal Participants..................................................63
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5.1.2. Inclusion Criteria – Infant Participants.......................................................66
5.2. Exclusion Criteria....................................................................................................66
5.2.1. Exclusion Criteria – Maternal Participants.................................................66
5.2.2. Exclusion Criteria – Infant Participants......................................................68
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants ................68
5.3. Lifestyle Considerations..........................................................................................69
5.4. Screen Failures ........................................................................................................69
6. STUDY INTERVENTION..................................................................................................69
6.1. Study Intervention(s) Administered........................................................................69
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........69
6.1.2. Placebo........................................................................................................70
6.1.3. Administration............................................................................................70
6.1.4. Medical Devices .........................................................................................70
6.2. Preparation/Handling/Storage/Accountability ........................................................71
6.2.1. Preparation and Dispensing........................................................................72
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................72
6.3.1. Blinding of Study Site Personnel................................................................72
6.3.2. Blinding of the Sponsor..............................................................................72
6.3.3. Allocation to Investigational Product .........................................................72
6.3.4. Breaking the Blind......................................................................................73
6.4. Study Intervention Compliance...............................................................................73
6.5. Concomitant Therapy..............................................................................................73
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................73
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................74
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................74
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................75
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................75
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications –
Infant Participants............................................................................................75
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6.6. Dose Modification...................................................................................................75
6.7. Intervention After the End of the Study..................................................................75
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................76
7.1. Discontinuation of Study Intervention ....................................................................76
7.2. Participant Discontinuation/Withdrawal From the Study.......................................76
7.3. Withdrawal of Consent............................................................................................76
7.4. Lost to Follow-up....................................................................................................77
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................77
8.1. Efficacy Assessments..............................................................................................78
8.1.1. Efficacy Assessments – Infant Participants................................................78
8.1.1.1. Midturbinate Nasal Swab Collection and Testing 
Requirements for Endpoint Confirmation – Infant Participants........79
8.1.1.2. Events for Adjudication and Submission Guidance –
Infant Participants..............................................................................79
8.1.2. Exploratory Efficacy Assessments – Maternal Participants.......................80
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal 
and Infant Participants .....................................................................................81
8.1.4. Immunogenicity Assessments ....................................................................81
8.1.4.1. Total Volume of Blood Collected – Maternal Participants.......81
8.1.4.2. Total Volume of Blood Collected – Infant Participants............81
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant 
Participants ........................................................................................82
8.1.4.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development – Maternal and Infant 
Participants ........................................................................................82
8.1.4.5. Respiratory Pathogens – Infant Participants .............................82
8.1.4.6. Biological Samples – Maternal and Infant Participants............83
8.2. Safety Assessments .................................................................................................83
8.2.1. Participant Electronic Diary – Maternal Participants .................................83
8.2.1.1. Local Reactions – Maternal Participants...................................84
8.2.1.2. Systemic Events – Maternal Participants..................................86
8.2.1.3. Temperature – Maternal Participants ........................................87
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8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant 
Participants.......................................................................................................88
8.3. Adverse Events and Serious Adverse Events..........................................................89
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......89
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................91
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................91
8.3.2. Method of Detecting AEs and SAEs ..........................................................92
8.3.3. Follow-up of AEs and SAEs.......................................................................92
8.3.4. Regulatory Reporting Requirements for SAEs...........................................93
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Investigational Product ..........................................................................93
8.3.5.1. Exposure During Breastfeeding ................................................93
8.3.5.2. Occupational Exposure .............................................................93
8.3.6. Cardiovascular and Death Events...............................................................94
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................94
8.3.8. Adverse Events of Special Interest.............................................................95
8.3.8.1. Lack of Efficacy........................................................................95
8.3.9. Medical Device Deficiencies......................................................................96
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........96
8.3.9.2. Follow-up of Medical Device Deficiencies...............................96
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................96
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................97
8.3.10. Medication Errors.....................................................................................97
8.4. Treatment of Overdose............................................................................................98
8.5. Pharmacokinetics ....................................................................................................98
8.6. Pharmacodynamics..................................................................................................98
8.7. Genetics...................................................................................................................98
8.7.1. Specified Genetics ......................................................................................98
8.8. Biomarkers ..............................................................................................................98
8.9. Health Economics ...................................................................................................99
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8.10. Procedures – Maternal Participants.......................................................................99
8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to 
Vaccination to Day 1 – Visit 1) .......................................................................99
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After 
Vaccination)...................................................................................................103
8.10.3. Delivery (Maternity Unit).......................................................................104
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 
210 Days After Delivery)...............................................................................105
8.10.5. Unscheduled Reactogenicity Visits........................................................106
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria –
Maternal Participants .....................................................................................108
8.11. Procedures – Infant Participants..........................................................................109
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After 
Birth)..............................................................................................................109
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After 
Birth)..............................................................................................................110
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 
Days After Birth) ...........................................................................................112
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 
Days After Birth) ...........................................................................................113
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days 
After Birth; Infant Participants Born During the First Year of the Study 
Only) ..............................................................................................................114
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 
742 Days After Birth; Infant Participants Born During the First Year of 
the Study).......................................................................................................115
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 
Months After Delivery)..................................................................................116
8.11.7.1. Study Visits Following a Medically Attended RTI –
Hospital, Home, or Clinic Visit.......................................................116
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit 
Criteria ...........................................................................................................118
8.12. Nasal Swab Collection ........................................................................................119
8.13. Communication and Use of Technology.............................................................120
9. STATISTICAL CONSIDERATIONS ..............................................................................121
9.1. Estimands and Statistical Hypotheses...................................................................121
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9.1.1. Estimands – Infant Participants ................................................................121
9.1.1.1. Efficacy ...................................................................................121
9.1.1.2. Immunogenicity ......................................................................122
9.1.1.3. Safety.......................................................................................122
9.1.2. Estimands – Maternal Participants ...........................................................122
9.1.2.1. Immunogenicity ......................................................................122
9.1.2.2. Safety.......................................................................................123
9.2. Sample Size Determination...................................................................................123
9.3. Populations for Analysis .......................................................................................124
9.4. Statistical Analyses ...............................................................................................125
9.4.1. Efficacy Analyses .....................................................................................125
9.4.2. Safety Analyses ........................................................................................128
9.4.3. Other Analyses..........................................................................................129
9.4.3.1. Immunogenicity Analyses.......................................................129
9.4.3.2. Healthcare Utilization Analyses..............................................130
9.5. Interim Analyses ...................................................................................................131
9.5.1. Data Monitoring Committee.....................................................................132
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................133
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............133
10.1.1. Regulatory and Ethical Considerations ..................................................133
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................133
10.1.2. Financial Disclosure ...............................................................................134
10.1.3. Informed Consent Process ......................................................................134
10.1.4. Data Protection .......................................................................................135
10.1.5. Dissemination of Clinical Study Data ....................................................136
10.1.6. Data Quality Assurance ..........................................................................137
10.1.7. Source Documents..................................................................................139
10.1.8. Study and Site Closure............................................................................139
10.1.9. Publication Policy...................................................................................139
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................140
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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................141
10.2.1. Definition of AE .....................................................................................141
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs).................142
10.2.3. Definition of SAE...................................................................................142
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs.....................144
10.2.5. Reporting of SAEs..................................................................................146
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......147
10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting............................................149
10.4.1. Definition of AE and ADE .....................................................................149
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device 
Effect, and Unanticipated Serious Adverse Device Effect............................150
10.4.3. Definition of Device Deficiency.............................................................150
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................151
10.4.5. Reporting of SAEs..................................................................................153
10.4.6. Reporting of SADEs...............................................................................153
10.5. Appendix 5: Background Factors........................................................................154
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria 
Checklist for MA-RTI Visit – Infant Participants...................................................155
10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only...............157
10.7.1. Informed Consent for the Maternal Participants <20 Years Old............157
10.7.2. Temperature Measurement and Definition of Fever ..............................158
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants.........158
10.7.3.1. Enrollment of Maternal Participants in the Sentinel 
Cohort..............................................................................................158
10.7.3.2. Conclusion of the Sentinel Cohort ........................................158
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or 
Telephone; 14 to 16 Days After Vaccination).................................159
10.7.3.4. Schedule of Activities for Maternal Participants Enrolled 
in the Sentinel Cohort in Japan........................................................160
10.7.4. Exclusion Criterion 12 Clarification.......................................................163
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10.7.5. Definitions of SAE, SAE Caused by Medical Device, and 
Unanticipated SAE Caused by Medical Device ............................................163
10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix –
Applicable to the Philippines, Gambia, and South Africa Only..............................164
10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to 
South Korea and Taiwan Only ................................................................................165
10.10. Appendix 10: Abbreviations .............................................................................166
11. REFERENCES ................................................................................................................169
LIST OF TABLES
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants ...............................................................................................52
Table 2.
Endpoint Events and Definitions in Maternal Participants.......................58
Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained....................................................................................................82
Table 4.
Grading Scale for Local Reactions...........................................................85
Table 5.
Grading Scale for Systemic Events ..........................................................87
Table 6.
Ranges for Fever.......................................................................................88
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals 
at an Interim Analysis.............................................................................132
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Indication
Pfizer’s respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSVpreF) 
is a prophylactic vaccine that is being investigated for the prevention of medically attended
RSV-associated lower respiratory tract illness (LRTI) in infants by active immunization of 
pregnant women.
Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given the global burden of disease, maternal immunization offers an attractive 
strategy for infant disease prevention.  Both preclinical studies in animals and interim data 
from a Phase 1/2 study in healthy nonpregnant adults have demonstrated acceptable 
tolerability and safety of RSVpreF.  A robust immune response has also been observed in 
participants from the aforementioned trial. RSVpreF is currently under assessment in healthy 
pregnant women 18 through 49 years of age (Study C3671003: A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blinded Trial to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT04032093).
The safety and tolerability of RSVpreF in pregnant adolescents has yet to be demonstrated. 
Vaccine-elicited immune responses with RSVpreF are expected to be similar in adolescents 
and women based on studies comparing maternal immunization with Tdap and HPV 
vaccination.  Infants born to adolescent mothers are known to be at a higher risk of 
prematurity, an important risk factor for RSV disease. Therefore, pregnant adolescents 
(18 years of age) are an appropriate pediatric population for RSVpreF maternal 
immunization, providing insight toward the efficacy, safety, and tolerability of the vaccine.
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
lower respiratory tract illness (MA-LRTI) in infants.
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Objectives, Estimands, and Endpoints 
Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC): 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants 
born to maternal 
participants receiving 
1 dose of investigational 
product, the percentage 
of participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

Adverse events (AEs) from birth to 
1 month of age.

Serious adverse events (SAEs) and 
newly diagnosed chronic medical 
conditions (NDCMCs):
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants 
enrolled during the first year of 
the study).
Secondary Efficacy Objectives
– Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV. 
Vaccine efficacy (VE), 
defined as the relative risk
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC): 

occurring within 210 days after birth.

occurring within 240 days after birth, 
if the analysis at 210 days meets 
efficacy criteria. 

occurring within 270 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 270 days meets 
efficacy criteria.
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Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of medically attended 
respiratory tract illness 
(MA-RTI) due to RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs 
from vaccination up to 730 days after 
birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 12 months 
of age.
MA-LRTIs due to RSV occurring 361 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth. 
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV in infants after 6 months 
of age.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA--LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population. 
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth. 
To assess the impact of 
RSVpreF on RSV illness based 
on socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
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To assess the effect of RSVpreF 
on healthcare utilization. 
Univariate summaries of healthcare 
utilization variables, which may include 
the following: number and type of 
medical visits, length of hospital stay, 
requirement for mechanical ventilation, 
requirement for respiratory diagnostic 
procedures, requirement for intravenous 
(IV) fluids, requirement for prescriptions, 
and antibiotic use.
To describe the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI, 
MA-LRTI, and severe 
MA-LRTI in premature infants 
<37 weeks of age.
MA-RTI, MA-LRTI, and severe 
MA-LRTI due to RSV occurring 0 to 
730 days after birth.
Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimand
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery 
study visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum
neutralizing titers and prefusion F 
immunoglobulin G (IgG) titers 
measured:

before vaccination.

at delivery.
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Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis section [Section 9.2]).  There is no specific case target for 
the additional primary endpoint of severe MA-LRTI. The total enrollment number of 
maternal participants may vary depending on the incidence rate of the primary endpoint in 
the infant participants, the true underlying VE, and a potential early stop for efficacy or 
futility. In the event that efficacy in the infant population is demonstrated at the interim 
analysis, enrollment of maternal participants may continue in order to obtain safety 
evaluations in an adequate number of maternal and infant participants to support vaccine 
registration with national health authorities.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It was anticipated that approximately 
6900 mother-infant pairs would be needed to accumulate 124 per-protocol cases prior to the 
global COVID-19 pandemic.  With the variable RSV season, the sample size may need to be 
increased and enrollment could go up to 10,000 maternal participants based on the number of 
cases of RSV.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF will be 120 µg 
(60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants. Note: Maternal participants 
will include adolescent females who may be referred to as “minors.” 
Information/assessments for minors may require parental/legal guardian 
awareness/approval per local regulations.
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Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study, all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term respiratory 
tract illness (RTI) surveillance and safety oversight to address safety and the possibility of 
conferred enhanced protection (antibody persistence) during a second RSV season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee.
Planned Duration
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on gestational age (GA) at the time of vaccination and 
when the infant is actually born.
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
Data Monitoring Committee
This study will use an external data monitoring committee (E-DMC) to monitor vaccine 
safety and efficacy and study futility.
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Statistical Methods
The primary hypothesis to be tested is that VE with respect to MA-LRTI due to RSV or 
severe MA-LRTI due to RSV in infants within at least 90 days after birth is more than 20%, 
relative to placebo. The 2 primary endpoints will be tested in parallel using a multiplicity 
adjustment procedure. VE will be estimated using the exact conditional binomial method. 
There will also be hierarchical testing of the primary endpoints to 120 days, 150 days, and 
180 days, conditional on success of the analysis for the shorter intervals. A single interim 
analysis of the MA-LRTI-due-to-RSV endpoint with the opportunity to stop the study for 
efficacy or futility may be included. At the end of the trial, the RSV vaccine may be deemed 
efficacious if there are 43 or fewer cases of MA-LRTI due to RSV in the RSV vaccine group 
out of the 124 total primary-endpoint cases.  This corresponds to estimated VE = 47% with 
95.1% confidence interval (CI) = (22%, 64%). For severe MA-LRTI, assuming a total of 
50 cases occur, the vaccine may be deemed efficacious if there are 14 or fewer cases in the 
RSV vaccine group.  This corresponds to estimated VE = 61% with 95.1% CI = (26%, 81%).
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1.2. Schematic for Study Participants
1.2.1. Study Design – Maternal Participants
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1.2.2. Study Design – Infant Participants
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Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
1.2.3. Schedule of Activities for Maternal Participants
Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current/former alcohol, tobacco, marijuana, or any illicit drug 
usage
X
Record vital signs
X
Targeted physical and obstetric examination performed on the same 
day or within 7 days before the vaccination visit
X
Record details of any antenatal and/or postnatal steroid treatment, 
monoclonal antibodies, blood products, or Rho(D) immune globulin
X
X
X
X
Record details of the maternal participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
Review eligibility criteria
X
X
X
Review temporary delay criteria
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Prevaccination blood draw for serologic assessment (~15 mL) on the 
same day or within 7 days before the vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and measuring devicef
X
Obtain and record baseline assessment of prespecified systemic events 
on the day of and prior to vaccination in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic assessment (~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X-------------------------- X
Record AEs, as appropriateh
X-------------------------- X
Record SAEs, as appropriateh
X
X
X
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of the 
schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; ICD = informed 
consent document; MA-RTI = medically attended respiratory tract illness.
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the LMP and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) a baseline 
assessment of prespecified systemic events on the day of and prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination 
(where Day 1 is the day of vaccination).  Remind maternal participants and their parent(s)/legal guardian (if a minor) that the study staff/field worker may 
contact them to obtain additional information on events entered into the e-diary.  Ask maternal participants or their parent(s)/legal guardian (if a minor) to 
contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 following vaccination, to determine if an 
unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal participant may be referred to the appropriate healthcare facility 
at the discretion of the study staff/field worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 28 days after vaccination.  From the signing of 
the ICD until the maternal participant completes the study, all SAEs will be collected. Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
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1.2.3.1. Schedule of Activities for Maternal Participants: RTI Surveillance for Medically Attended Respiratory Tract Illness
Visits (Vaccination Until the End-of-Study Visit)
Visit Description
Assessments of MA-RTIa
Visit Window
As Soon as Possible After Confirmed MA-RTI 
Type of Visit
Telephone
Record details of a confirmed MA-RTI 
X
Details of an acute illness visit AND a report of 1 or more of the following RTI
signs and symptoms: 

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
X
Obtain standard-of-care records, including local NAAT testing results (if 
applicable)b
X
Record nonstudy vaccine information
X
Record AEs and SAEs, as appropriatec
X
Complete the CRF with details 
X
Abbreviations: CRF = case report form; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness.
a.
Confirmed cases of MA-RTI will be collected from vaccination until the maternal participant completes the study. The assessment of the event would 
involve a telephone call, or a clinic visit if determined by the investigator to be warranted. 
b.
Site staff will review and collect data pertaining to the illness and any local NAAT testing results (RSV, influenza, etc), if available.
c.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  MA-RTI events will not be captured as safety 
events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to have resulted in death. Please see 
Section 8.3.1 for reporting requirements and timelines.
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1.2.4. Schedule of Activities for Infant Participants
Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Assign infant participant identifier
X
Demography 
X
Collect background factorsc
X
X
X
X
X
X
Collect birth outcome information including 
infant’s birth data and appearance, pulse, grimace, 
activity, and respiration (Apgar) score
X
Obtain and record infant’s length, head 
circumference, and weight
X
X
X
X
(if clinic visit)
X
(if clinic visit)
Physical examination including vital signs
(temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate) performed within 48 hours 
after birth
X
Obtain and record vital signs, including 
temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate
X
Targeted physical examination (record in the site 
source document)
X
X
X
(if clinic visit)
X
(if clinic visit)
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, 
packed cells)
X
X
X
X
X
X
Review eligibility
X
Cord blood sample (~10 mL) for serologic 
assessmentd
X
Record AEs, as appropriatee
X
Record NDCMCs and SAEs, as appropriatee
X
X
X
X
X
X
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Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Surveillance reminder contact
Contact with the infant 
participants’ parent(s) or legal 
guardian(s) approximately 
every week until Visit 3
From Visit 3, contact with the infant participant’s parent(s) or legal guardian(s), 
approximately every 28 to 35 days until the end of the study
Assessment of MA-RTIsf,g
Assessment of MA-RTI events 
during the active RSV 
surveillance period as detailed 
in Section 1.2.4.1 of the 
schedule of activities
Assessment of MA-RTI events as detailed in Section 1.2.4.1 of the schedule of 
activities
Abbreviations: MA-RTI = medically attended respiratory tract illness; NDCMC = newly diagnosed chronic medical condition; RSV = respiratory syncytial 
virus; SpO2 = oxygen saturation.
a.
Applicable only for infant participants enrolled during the first year of the study.
b.
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), study visits that cannot be conducted in the clinic or at home, in 
accordance with the protocol requirements, may be conducted via telephone. 
c.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV illness. 
d.
Cord blood must be obtained on the day of birth. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical cord has 
been clamped and cut. If cord blood is unavailable, a blood sample may be collected from the infant participant preferably within the first 24 hours but up 
to 7 days after birth. The infant’s weight must be used to determine the volume of blood that can be collected.
e.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs, NDCMCs, and SAEs through 28 days after birth.  From 
29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected.  An NDCMC is defined as a disease or medical 
condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
f.
A confirmed MA-RTI is defined as an expected study event based on the assessments detailed in the schedule of assessment in Section 1.2.4.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
g.
Reporting MA-RTI events should commence 72 hours after the infant’s delivery.  Respiratory distress events associated with and within 72 hours of birth 
should not be captured as MA-RTI events on the study but should be captured as AEs/SAEs (if applicable).
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1.2.4.1. Schedule of Activities for Infant Participants: Respiratory Tract Illness Study Visits During the Study 
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Surveillance reminder contact
Contact the infant participants’ parent(s) or 
legal guardian(s) approximately every week 
until Visit 3
From Visit 3, contact the infant participants’ parent(s) or legal 
guardian(s), approximately every 28 -35 days until the end of the 
study
Record confirmed MA-RTI as detailed in Appendix 6, as 
appropriate
X
X
X
Record details of the RTI, including 1 or more of the 
following RTI signs and symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid 
breathing for any duration

Cough

Inability to feed for any duration because of 
respiratory symptoms

Apnea

Any other respiratory symptom of concern 
X
X
X
Obtain standard-of-care records and complete CRFc
X
X
X
Record local NAAT testing results, if performed and 
availabled
X
X
X
Perform RTI study visit, record targeted assessment
results (temperature, heart rate, respiratory rate, SpO2 by 
pulse oximetry, chest wall indrawing) and body weight, and 
collect nasal swab (for RT-PCR)e
X
X
Record concomitant medication associated with the 
treatment of the MA-RTI
X
X
X
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Collect background factors associated with MA-RTIf.
X
X
X
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, packed 
cells)
X
X
X
Record AEs , NDCMCs, and SAEs, as appropriateg
X
X
X
Compile MA-RTI visit source documentation upon 
request by adjudication committee (qualifying 
RSV-positive cases only)
X
X
Abbreviations: CRF = case report form; HCP = healthcare provider; ICU = intensive care unit; IV = intravenous; MA-LRTI = medically attended lower 
respiratory tract illness; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; NDCMC = newly diagnosed 
chronic medical condition; RSV = respiratory syncytial virus; RTI = respiratory tract illness; RT-PCR = reverse transcription–polymerase chain reaction; 
SpO2 = oxygen saturation.
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed 
MA-RTI and Within 72 Hours
(Preferable) or Up to 10 Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
a.
If the infant participant is reported to be experiencing or has had an MA-RTI from birth until Visit 3, the site should arrange a study visit as soon as possible 
and within 72 hours (preferable) or up to 10 days. Ideally, the RTI study visit will be conducted at the investigational study site; however, it is possible that 
the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit where the infant 
participant is residing. Note: Reporting MA-RTI events should commence 72 hours after the infant’s delivery.  
b.
If the infant participant is reported to be experiencing or has had an MA-RTI associated with severe LRTI criteria or been hospitalized for an RTI from Visit 
3 until the end of study participation, the site should arrange a visit as soon as possible and within 72 hours (preferable) or up to 10 days of site awareness. 
Ideally, assessment of these potential endpoint events (hospitalization due to RTI or severe MA-LRTI) will be conducted at the investigational study site; 
however, it is possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff 
may visit where the infant participant is residing. Note: For nonsevere MA-RTIs, a telephone contact with the infant participants’ parent(s) or legal 
guardian(s) is acceptable to complete the study visit.
c.
Obtain case records, including details of hospitalization, ICU stays, use of oxygen, IV fluids usage, etc.
d.
The site staff/field worker will review and collect data related to any local NAAT testing results, if performed and available.
e.
The site staff/field worker will collect nasal swabs for confirmed MA- RTIs, including confirmed cases of hospitalizations due to an RTI and severe MA-
LRTIs. In the event that restrictions prevent taking RTI study swabs because of an outbreak, pandemic situation, or natural disaster, the study nasal swab 
can be collected for processing at Pfizer’s central laboratory by the infant caregiver, during or within 10 days following an MA-RTI visit, or by the HCP 
assessing the infant during the MA-RTI visit (in addition to any samples obtained in the course of routine clinical care) as detailed in Section 8.11.7.1 and 
Section 8.11.8.
f.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV. This will be collected for 
all MA-RTI events reported.
g.
The investigator and site staff/field worker will ensure the active elicitation and collection of NDCMCs and SAEs through the end-of-study visit for the 
infant participant. From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected. An NDCMC is defined 
as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma). Note: A 
confirmed MA-RTI will not be captured as a safety event, unless the investigator or an appropriate designee deems it to be related to the investigational 
product or to have resulted in death.
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2. INTRODUCTION
Prevention of RSV disease in young infants is a significant unmet medical need globally.  
RSV is the leading cause of bronchiolitis and viral pneumonia in infants and can lead to fatal 
respiratory distress, especially in those with risk factors including premature infants with 
underlying cardiopulmonary disease, or in the absence of effective healthcare systems.1
However, most cases of RSV disease occur in healthy, full-term infants without risk factors.2
Worldwide, RSV kills approximately 118,200 children annually, with about half of those 
deaths occurring in infants under 6 months of age, and the majority of those occurring in 
resource-limited countries.3,4 In the United States, RSV is the leading cause of infant 
hospitalization, with more than 60,000 hospitalizations of children 12 months of age and 
younger annually.5,6  There is increasing evidence that the link between severe RSV disease 
in infancy and wheezing later in childhood may be causal.7,8  Like influenza, RSV infection 
follows a seasonal pattern, causing illness primarily in the cooler months of the year in 
temperate regions and during the wet season in tropical countries with seasonal rainfall.9  
Infection is essentially universal by the time children reach 2 years of age.10
Currently, there is neither specific treatment for RSV infection nor a vaccine to protect 
against RSV disease.  Treatment consists primarily of supportive care.  A prophylactic 
humanized monoclonal antibody, palivizumab (Synagis, AstraZeneca), targeting the RSV F 
glycoprotein is available for prevention of severe RSV disease in young infants at increased 
risk.11  Limitations of its use include its high cost12 and requirement of multiple monthly 
injections,13 and so it remains recommended for use only in very premature infants and 
others at increased risk of severe illness.6,14
Nevertheless, the protective effect of Synagis provides definitive proof of principle that 
serum neutralizing antibody directed against the F protein can provide clinically meaningful 
protection against RSV lower respiratory tract disease in young infants.15  Furthermore, it is 
well known that in other disease settings, antibodies transferred from mothers to their fetuses 
across the placenta can reduce infant disease early in life,16,17,18,19,20,21 suggesting that 
maternal immunization is a reasonable approach to RSV disease prevention among young 
infants.
There are 2 antigenic variants of RSV, namely, RSV subgroup A (RSV A) and RSV 
subgroup B (RSV B).  The RSV vaccine being investigated in this study is a bivalent vaccine 
composed of stable RSV prefusion F antigens representing the 2 subgroups to help ensure the 
broadest coverage against RSV illness.
RSVpreF is a prophylactic vaccine being developed to prevent medically attended
RSV-associated LRTI in infants by active immunization of pregnant women.
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2.1. Study Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given a global burden of disease in the millions of cases each year, maternal 
immunization offers an attractive strategy for infant disease prevention.  Both preclinical 
studies in animals and interim data from a Phase 1/2 study in healthy nonpregnant adults 
have demonstrated acceptable tolerability and safety of RSVpreF.  A robust immune 
response has also been observed in the population of the aforementioned trial, at 1 month 
after vaccination. The combined RSV A and B serum neutralization geometric mean titers 
(GMTs) have been shown to be 12 to 20 times higher than those with 100 μg/mL of
palivizumab, the concentration of the monoclonal antibody that is known to provide near to 
complete protection of high-risk infants from severe RSV disease.22,23 RSVpreF is currently 
under assessment in healthy pregnant women 18 through 49 years of age (Study C3671003, 
A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093).
The safety and tolerability of RSVpreF in pregnant adolescents has yet to be demonstrated. 
Vaccine-elicited immune responses with RSVpreF are expected to be similar in adolescents 
and women based on studies comparing maternal immunization with Tdap and HPV 
vaccination.24,25,26  Infants born to adolescent mothers are known to be at a higher risk of 
prematurity, an important risk factor for RSV disease.27,28 Therefore, pregnant adolescents 
(18 years of age) are an appropriate pediatric population for RSVpreF maternal 
immunization, providing insight toward the efficacy, safety, and tolerability of the vaccine.
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
RSV-associated LRTI in infants.
2.2. Background 
RSV is an important cause of morbidity and mortality worldwide, with a substantial burden 
of disease borne by young infants.  Rates of severe RSV illness are highest in infants 
6 months of age, with a peak in hospitalization between 1 and 2 months of life, though the
highest case-fatality rates are observed in the neonatal period (<1 month).2 Infants born 
prematurely and those with underlying cardiac or pulmonary disease are at further increased 
risk of severe clinical disease due to RSV.  A 2017 retrospective case analysis that examined 
RSV mortality data from 23 countries demonstrates the global nature of the seriousness of 
RSV disease, with significant morbidity and mortality occurring in both lower- and 
middle-income countries (LMICs) and high-income countries.3,4
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No specific treatments for RSV exist, and available prophylactic measures (ie, RSV 
monoclonal antibody) are limited to use in only those infants at highest risk; additionally, in 
LMICs, use of available RSV prophylaxis is cost-prohibitive.  While active immunization 
against RSV in infants might be an option, multiple efforts, extending over half a century, to 
develop a safe and effective RSV vaccine to protect infants from disease have yielded little 
success.  The early peak of disease presents a further obstacle to an active vaccination 
strategy for infants.  Given these challenges, maternal immunization to protect infants early 
in life offers an attractive strategy for infant disease prevention.
The present RSV vaccine efforts were initiated in early 2014 based on a new scientific 
discovery (determination of the RSV prefusion F crystal structure)29 and a changing 
regulatory and policy environment that today supports the development of vaccines for 
maternal immunization to protect very young infants.  The trimeric RSV F surface 
glycoprotein in a prefusion conformation is now known to be the primary target of 
neutralizing antibodies and is the basis for the engineered antigens in Pfizer’s vaccine 
candidate.   Applying structure-guided vaccine design, Pfizer has developed a stabilized RSV 
prefusion F vaccine candidate.  The core hypothesis underlying Pfizer’s RSV vaccine 
development effort for prevention of infant disease is that vaccine antigens based on RSV 
prefusion F, when administered to pregnant women in the second or third trimester of 
pregnancy, will elicit sufficiently high neutralizing antibody titers that, when the antibodies
are actively transferred transplacentally to the fetus, will protect infants against RSV disease. 
The aim is for neutralizing antibody levels to be at sufficient levels such that infants will be 
protected from birth and possibly through their first RSV season.
2.3. Benefit/Risk Assessment
RSVpreF is being evaluated in ongoing clinical studies.  Pfizer’s maternal immunization 
approach circumvents the risk of vaccine-mediated disease enhancement that was observed 
in the 1960s following direct immunization of RSV-naive infants with a formalin-inactivated 
RSV vaccine (FI-RSV).30  FI-RSV elicited a predominantly nonneutralizing antibody 
response and a Th2-biased cell-mediated response, both of which are considered potential 
contributing factors to disease enhancement.31  During preclinical studies, in a standard 
cotton rat infectious RSV challenge model, FI-RSV showed pathological signs of causing 
disease enhancement, and the current Pfizer vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease enhancement has not been reported to occur in 
RSV-experienced individuals after immunization with any RSV vaccine candidate.  Because 
pregnant women are universally RSV-experienced, they are not considered at risk for a 
disease-enhancing immune response to the vaccine that could exacerbate infection in 
themselves.  Enhanced disease has not been observed in infants born to mothers who
received prior investigational RSV vaccines; therefore, enhanced disease in infants is very
unlikely.  A previous study of maternal immunization with a Wyeth (later merged with 
Pfizer) investigational RSV vaccine (PFP-2) showed an acceptable safety profile, even 
though this candidate contained a postfusion RSV F antigen that elicited a relatively weak 
RSV-neutralizing antibody response and a higher nonneutralizing RSV-binding antibody 
response in pregnant women.32  A recently completed Phase 3 maternal RSV trial (Novavax) 
with an RSV vaccine containing F not stabilized in the prefusion form, given to over 
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4600 healthy pregnant volunteers, showed a similar safety profile in the RSV vaccine and 
placebo groups.33
Vaccination with the RSV prefusion F antigens elicits a higher ratio of neutralizing to 
nonneutralizing antibodies, more closely matching the profile in naturally exposed 
individuals.  The safety profile of RSVpreF observed to date is similar to that of prior RSV F 
subunit vaccines tested in RSV-experienced adults.
There are limited data on the global burden of maternal RSV infection, likely in part because 
of infrequent diagnostic testing. However, in one multisite study, RSV-associated disease in 
pregnancy was shown to result in prolonged hospitalization and an increased likelihood of 
preterm birth in women who tested RSV-positive.34 It is possible that vaccination may 
benefit the pregnant women who receive it. RTI in mothers who receive RSVpreF will be 
explored in this study.  The benefit of maternal vaccination is accrued to the infant by means 
of transplacental antibody transfer.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the investigator’s brochure (IB), which is the 
single reference safety document (SRSD) for this study.
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Infant Participants
The study objectives and endpoints for infant participants employ the event definitions in 
Table 1.
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study Endpoints/Assessments
Study Definitions
Medically attended visit
Infant participant has been taken to or seen by a healthcare provider 
(eg, outpatient or inpatient visit, emergency room, urgent care, or home 
visit)
MA-RTI visit for infant 
participant
A medically attended visit AND 1 or more of the following RTI signs and 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any 
duration

Cough

Inability to feed for any duration because of respiratory symptoms

Apnea

Any other respiratory symptom of concern 
RSV-positive testa

RSV RT-PCR–positive test result by Pfizer central laboratory
OR

RSV-positive test result by certified laboratory with NAAT for RSV
MA-RTI due to RSVb

An MA-RTI visit 
AND

RSV-positive test result as described in Section 8.1.1.1
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Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study Endpoints/Assessments
Study Definitions
MA-LRTI due to any cause

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age], 
≥50 bpm for ≥2 months to <12 months of age, or ≥40 bpm for 
≥12 months to 24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
MA-LRTI due to RSVb

Infant with an MA-RTI visit 
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age] or 
≥50 bpm for ≥2 to <12 months of age, or ≥40 bpm for ≥12 months to 
24 months of age) OR

SpO2 <95% OR

Chest wall indrawing 
AND 

RSV-positive test result as described in Section 8.1.1.1
Hospitalized RTI due to RSVb
An RTI due to RSV that results in hospitalization
Severe MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥70 bpm for <2 months of age [<60 days of age], 
≥60 bpm for ≥2 months to <12 months of age, or ≥50 bpm for 
≥12 months to 24 months of age) OR

SpO2 <93% OR

High-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive) OR

ICU admission for >4 hours OR

Failure to respond/unconscious 
AND

RSV-positive test result as described in Section 8.1.1.1
Protocol-defined primary 
endpoint

Any MA-LRTI or severe MA-LRTI due to RSV as determined by an 
EAC
Abbreviations: bpm = breaths per minute; EAC = endpoint adjudication committee; ICU = intensive care unit; 
MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically attended respiratory tract 
illness; NAAT = nucleic acid amplification technology; RR = respiratory rate; RSV = respiratory syncytial 
virus; RTI = respiratory tract illness; SpO2 = oxygen saturation.
a.
RSV-positive testing is defined as a positive RSV test (see Section 8.1.1.1) conducted on a sample 
obtained during the medically attended visit or within 10 days (where Day 1 is the day of the MA-RTI 
visit) as detailed in Section 8.11.7.
b.
The EAC will determine if the endpoint criteria have been met upon review of the site source 
documentation from the MA-RTI visit and RTI study visits, including all available RSV test results.
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Study Objectives – Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI due 
to RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants born 
to maternal participants 
receiving 1 dose of 
investigational product, 
the percentage of 
participants with each
safety endpoint in each 
vaccine group.

Specific birth outcomes.

AEs from birth to 1 month of age.

SAEs and NDCMCs:
o
from birth through 6 months of 
age (first RSV season for all infant 
participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants enrolled 
during the first year of the study).
Secondary Efficacy Objectives –
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 180 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV. 
Vaccine efficacy (VE), defined 
as the relative risk reduction of 
the endpoint in the RSV 
vaccine group compared to the 
placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC): 

occurring within 210 days after birth.

occurring within 240 days after birth, 
if the analysis at 210 days meets 
efficacy criteria. 

occurring within 270 days after birth, 
if the analysis at 210 days meets 
efficacy criteria.

occurring within 360 days after birth, 
if the analysis at 270 days meets 
efficacy criteria.
Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI due to 
RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs from 
vaccination up to 730 days after birth.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 12 months of 
age.
MA-LRTIs due to RSV occurring 361 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI due 
to RSV in infants after 6 months 
of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV in infants after 6 months of 
age.
Hospitalization due to RSV occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI in 
the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
To assess the impact of RSVpreF 
on RSV illness based on 
socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
To assess the effect of RSVpreF 
on healthcare utilization.
Univariate summaries of healthcare 
utilization variables, which may include the 
following: number and type of medical 
visits, length of hospital stay, requirement 
for mechanical ventilation, requirement for 
respiratory diagnostic procedures,
requirement for IV fluids, requirement for 
prescriptions, and antibiotic use.
To describe the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI, MA-LRTI, 
and severe MA-LRTI in 
premature infants <37 weeks of 
age.
MA-RTI, MA-LRTI, and severe MA-LRTI
due to RSV occurring 0 to 730 days after 
birth.
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3.2. Maternal Participants
The study objectives and endpoints for maternal participants employ the event definitions in 
Table 2.
Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
Maternal medically attended visit
The maternal participant reports a visit with a healthcare 
provider (eg, outpatient or inpatient visit, emergency room, 
urgent care, or home visit)
MA-RTI visit maternal participant
A medically attended visit AND 1 or more of the following 
RTI signs and symptoms:

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
Abbreviations: MA-RTI = medically attended respiratory tract illness; RTI = respiratory tract illness.
Study Objectives – Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimands
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery study 
visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum neutralizing 
titers and prefusion F IgG titers 
measured:

before vaccination.

at delivery.
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3.3. Protocol-Defined Efficacy Endpoints 
All infant participants experiencing an MA-RTI will have an RTI study visit as detailed in
Section 8.1.  This protocol will use an independent EAC to determine whether certain 
investigator-reported events meet the definition of disease-related efficacy endpoints, using 
predefined endpoint criteria as summarized in Table 1. Members of this EAC will be blinded 
to the vaccine assignment to allow for unbiased assessments.
Recognizing that RSV disease is a dynamic illness, sites will be instructed to submit all 
available source documentation for adjudication from the MA-RTI visit and to record data 
from the worst day of illness in the electronic case report form (eCRF).  The EAC will 
determine if the endpoint criteria have been met upon review of the site source
documentation from the MA-RTI visit, including data collected at the RTI study visit, and all 
available RSV testing.  Further information about the EAC will be detailed in the 
adjudication charter, including specific descriptions of the scope of its responsibilities and 
the process and definitions to review and assess study endpoints.
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition and 
constitute a study endpoint will not be recorded as AEs.  For those AEs that are handled as 
disease-related efficacy endpoints, a data monitoring committee (DMC) will conduct 
unblinded reviews on a regular basis throughout the trial (see Data Monitoring Committee,
Section 9.5.1).
Nonendpoint events (eg, an event that is determined not to be an MA-RTI) must be evaluated 
for safety reporting as per the protocol requirements.  Any AE that is adjudicated by the EAC
to not meet any endpoint criteria will be reported back to the investigator site of incidence; 
the investigator at the site must evaluate the event for safety as described in Appendix 2 of 
this protocol.  If the event is classified as serious, the investigator’s SAE awareness date in 
this instance is identified as the date on which the investigator site receives the nonendpoint 
SAE back from the EAC.  Handling these SAEs in this manner will allow Pfizer to meet its 
sponsor reporting obligations to regulatory authorities upon receipt of such SAEs.
Any events that remain unadjudicated at the annual safety report cutoff date will not be 
included in the safety tables of the report.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons. 
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This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of 
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis (Section 9.2). There is no specific case target for the 
additional primary endpoint of severe MA-LRTI. The total enrollment number of maternal 
participants may vary depending on the incidence rate of the primary endpoint in the infant 
participants, true underlying VE, and a potential early stop for efficacy or futility. In the 
event that efficacy in the infant population is demonstrated at the interim analysis, enrollment 
of maternal participants may continue in order to obtain safety evaluations in an adequate 
number of maternal and infant participants to support vaccine registration with national 
health authorities. Enrollment will be monitored to ensure even distribution of vaccination 
across gestational age between 24 0/7 and 36 0/7 weeks.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It was anticipated that approximately 
6900 mother-infant pairs would be needed to accumulate 124 per-protocol cases prior to the 
global COVID-19 pandemic.  With the variable RSV season, the sample size may need to be 
increased and enrollment could go up to 10,000 maternal participants based on the number of 
cases of RSV.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF for this study will be 
120 µg (60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.
Note: Maternal participants will include adolescent females who may be referred to as 
“minors.”  Information/assessments for minors may require parental/legal guardian 
awareness/approval per local regulations.
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term RTI 
surveillance and safety oversight to address safety and the possibility of conferred enhanced 
protection (antibody persistence) during a second RSV season. 
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All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. In addition, this study will use an 
E-DMC to monitor vaccine safety and efficacy and study futility.
4.1.1. Approximate Duration of Participation for Each Participant
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on GA at the time of vaccination and when the infant is 
actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth. 
4.1.2. Approximate Number of Participants
Healthy pregnant women will be randomly assigned to a study intervention. It was 
anticipated that approximately 6900 mother-infant pairs would be needed to accumulate 
124 per-protocol cases as defined in Section 9.2 of the protocol prior to the global COVID-19 
pandemic.  With the variable RSV season, the sample size may need to be increased and 
enrollment could go up to 10,000 maternal participants based on the number of cases of 
RSV.  Enrollment will be monitored to ensure that participants will be recruited from both 
the northern and southern hemispheres. Enrollment may vary depending on the incidence in 
the placebo group, the true underlying VE, the dropout rate, and a potential early stop for VE
or futility.
4.2. Scientific Rationale for Study Design
Refer to Section 2.1.
4.3. Justification for Dose
The final dose and formulation of RSVpreF selected for use in this study is based on the 
safety and immunogenicity data from the ongoing C3671003 maternal immunization study
(A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093) and the first-in-human (FIH) study C3671001.
The FIH study was designed to describe the safety, tolerability, and immunogenicity of 
6 RSVpreF candidates with bivalent formulations (RSV A and B) at 3 escalating dose levels 
of 60 µg (30 µg A and 30 µg B), 120 µg (60 µg A and 60 µg B), and 240 µg (120 µg A and 
120 µg B) of the RSV prefusion F antigen, with or without Al(OH)3, when administered 
alone or concomitantly with seasonal inactivated influenza vaccine.  The study utilizes a 
sentinel cohort (N=168; Phase 1) and an expanded cohort (N=1014; Phase 2).  Nonpregnant 
female and male study participants of 2 age groups, 18 through 49 years of age and 
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50 through 85 years of age, were enrolled into both cohorts.  The age groups are being run in 
parallel. 
An interim analysis of participants 18 through 49 years of age, including safety and 
tolerability (n=533) and immunogenicity (n=513) data up to 1 month after vaccination in the 
expanded cohort and additional immunogenicity data up to 3 months after vaccination in the 
sentinel cohort, has shown the RSVpreF candidate to be immunogenic and well tolerated. 
Local reactions and systemic events were noted to be predominantly mild or moderate across 
all doses and formulations, which is consistent with the current safety profile. The safety 
results from this planned interim analysis of healthy male and nonpregnant female 
participants 18 through 49 years of age are consistent with those from the sentinel-cohort 
analysis and indicate that RSVpreF has an acceptable safety profile and is well tolerated.
The immunogenicity results showed that RSVpreF elicited neutralizing titer geometric mean 
fold rises (GMFRs) of 10 to 20, 1 month after vaccination, depending on the formulation. 
Similarly, across all dose levels, with and without Al(OH)3, RSVpreF elicited high 
1-month-postvaccination RSV A and RSV B neutralizing GMTs. Overall, RSVpreF elicited 
anti–prefusion F immunoglobulin G1 (IgG1) responses that paralleled the elicited 
RSV-neutralizing responses. The ratio of RSV 50% neutralizing antibody titer GMFRs to 
prefusion RSV F binding IgG1 titer GMFRs (calculated with combined data for subgroups A 
and B) for the sentinel and expanded 18 through 49 years of age cohorts combined ranged 
from 0.62 to 0.76. The IgG1 and neutralization responses were similar in antigen-level dose
response, in equivalence of RSV A titer GMFRs to RSV B titer GMFRs, and in a lack of 
effect of Al(OH)3. 
Safety data for 403 mother/infant pairs, from maternal participants through 1 month after
maternal vaccination and for their infants from birth through the first month of life, in 
Study C3671003 provide further evidence of the safety of RSVpreF in maternal vaccine 
recipients, and initial evidence of the safety of maternal vaccination with RSVpreF for the 
infant. In maternal participants, solicited symptoms were generally mild to moderate in 
intensity and of short duration. Unsolicited AEs were consistent with anticipated events in 
this participant population and did not indicate any differences between RSVpreF and control 
recipients. No differences in pregnancy (eg, reports of preterm delivery or obstetric 
complications) and birth outcomes (eg, reports of respiratory distress at delivery or presence 
of congenital anomalies) were observed between RSVpreF and control recipients. No 
differences in the number or types of AEs reported were observed between infants born to 
mothers receiving RSVpreF and those receiving placebo in the first month of life.
The high ratio of RSV-neutralizing antibody titer GMFRs to prefusion F–binding titer 
GMFRs elicited by Pfizer’s RSVpreF candidate indicates that most of the elicited antibody 
can neutralize the virus. It is assumed that this reflects the ability of the antibodies to prevent 
RSV disease in immunized participants and, in the case of maternal immunization, prevent 
disease in their infants.
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The primary mechanism for protection of infants by the RSV maternal vaccine is 
neutralization of the virus by transplacentally transferred antibody, which is increased by 
immunization.  Maternal antibody decays exponentially in infants.  Therefore, it is 
anticipated that higher titers of transferred neutralizing antibodies will provide greater levels 
and durations of infant protection.  Results from the C3671001 FIH trial were used to 
determine the doses and formulations that are currently under investigation in the Phase 2b 
maternal immunization study: 120 µg or 240 µg of RSVpreF with or without Al(OH)3. 
These doses are expected to provide the greatest potential level of transplacental antibody 
transfer to infants and, therefore, the greatest potential benefit.  The dose and formulation of 
RSVpreF for the Phase 3 study was determined by the evaluation of the 1-month safety, 
tolerability, and immunogenicity results from the C3671003 maternal Phase 2b trial,
including infant RSV-neutralizing titers at birth.
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last visit.
The end of the study is defined as the date of the last visit of the last infant participant in the 
study. The study may also be terminated earlier for efficacy or futility as described in
Section 9.5.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
5.1.1. Inclusion Criteria – Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply 
(refer to the investigator site file [ISF] for further eligibility details regarding region-specific 
timing of vaccination with respect to RSV seasonality and maternal gestational age at 
vaccination):
Note: In countries/locales where study procedures used to determine eligibility criteria 
(eg, ultrasound examination, human immunodeficiency virus [HIV] testing, syphilis testing) 
are not performed as part of routine prenatal care, they must be performed as part of this 
clinical trial and reviewed by the investigator or qualified designee within 28 days prior to 
randomization.  Maternal participants must provide informed consent prior to 
performing any procedures, including those that are being done exclusively to meet 
study eligibility criteria.
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Note: Country-specific modifications associated with the study eligibility criteria are 
documented in Appendix 7, Appendix 8, and Appendix 9.
Age and Sex:
1. Healthy women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation 
on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are 
at no known increased risk for complications. 
Note: GA must be based upon 1 of the following composite criteria based on timing and 
availability of data on the last menstrual period (LMP) and an ultrasound examination 
performed in the first or second trimester.35  The earliest ultrasound data available during 
the current pregnancy should be used. In countries where the routine practice is for the 
GA determination to be based upon the first trimester ultrasound examination alone, 
without the LMP, this routine practice will be accepted.
a.
First-trimester data available (data obtained at ≤13 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a first-trimester ultrasound examination.

If there is a discrepancy of >5 days between the LMP-determined GA and an 
ultrasound result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA 
should be determined using the first-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and an 
ultrasound result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, 
then the GA should be determined using the first-trimester ultrasound result.
b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a second-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and the 
ultrasound result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >10 days between the LMP-determined GA and the 
ultrasound result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >14 days between the LMP-determined GA and the 
ultrasound result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
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Type of Participant and Disease Characteristics:
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Receiving prenatal standard of care based on country requirements.
4. Had a fetal anomaly ultrasound examination performed at ≥18 weeks of pregnancy with 
no significant fetal abnormalities observed. 
5. Determined by medical history, physical examination, and clinical judgment to be 
appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) 
surface antigen test during this pregnancy and prior to randomization (Visit 1). 
7. Intention to deliver at a hospital or birthing facility where study procedures can be 
obtained. 
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol OR
If the maternal participant is illiterate, a thumbprinted informed consent must be 
obtained, which must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process confirming that the maternal participant 
has been informed of all pertinent aspects of the study.
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5.1.2. Inclusion Criteria – Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a 
thumbprinted informed consent must have been obtained, which must have been signed 
and dated by an impartial witness who was present throughout the entire informed 
consent process confirming that the maternal participant/parent(s)/legal guardian(s) has 
been informed of all pertinent aspects of the study for herself (maternal participant) and
her fetus/infant prior to taking part in the study.
Note: Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements. 
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
5.2. Exclusion Criteria 
5.2.1. Exclusion Criteria – Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not 
available, the BMI at the time of the first obstetric visit during the current pregnancy may 
be used.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any related 
vaccine.
4. Current pregnancy resulting from in vitro fertilization.  Participants known to have used 
clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are 
permitted.
5. Current pregnancy complications or abnormalities at the time of consent that will 
increase the risk associated with the participation in and completion of the study, 
including but not limited to the following:

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.
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
Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated 
hypothyroidism.  This also includes disorders of glucose intolerance (eg, diabetes 
mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if 
uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the 
investigator’s judgment, that will increase the risk associated with the participation in and 
completion of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks’ gestation.

Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or significant congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the maternal 
or infant participant’s participation in, and completion of, the study or could preclude the 
evaluation of the maternal participant’s response (includes positive serologic testing for 
regional endemic conditions assessed during routine maternal care, as per local standards 
of care and obstetric recommendations).
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment.
9. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to 
consent and/or during study participation.
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11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of 
systemic corticosteroids for >14 days within 28 days prior to study enrollment.  
Prednisone use of <20 mg/day for ≤14 days is permitted. Inhaled/nebulized, 
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
12. Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an 
exclusion criterion for the study when elicited in participant screening, though it may be 
considered illicit in some locales.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before 
investigational product administration, or planned receipt through delivery, with 
1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt 
during study participation. Note: Licensed COVID-19 vaccines or COVID-19 vaccines 
authorized for temporary or emergency use will not be prohibited during the course of 
this study.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
5.2.2. Exclusion Criteria – Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and if no other exclusion criteria are met.  
The prevaccination blood draw and vaccination should take place on the same day. In the 
event that this is not possible, the prevaccination blood draw is also permissible within 7 days 
before the vaccination visit.

Current febrile illness (body temperature ≥38°C [≥100.4°F]) or other acute illness within 
48 hours before investigational product administration.

Diagnosed malaria within the last 7 days prior to investigational product administration.
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
Receipt of any inactivated vaccine (including full-dose regimen of licensed COVID-19 
vaccines or full-dose regimen of COVID-19 vaccines authorized for temporary or 
emergency use) within 14 days or any live vaccine within 28 days before investigational 
product administration.

If systemic corticosteroids (equivalent of ≥20 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical 
study but are not subsequently randomly assigned to investigational product. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs.
Maternal participants who do not meet the criteria for participation in this study (screen 
failure) may be rescreened. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
For this study, the investigational product(s) are RSVpreF and placebo (lyophile match).
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine 
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.  The
RSV drug product will be 120 µg of the RSV prefusion F antigen.  The drug product is 
supplied as a lyophilized white cake in a 2-mL glass vial, with a 13-mm lyophilization 
stopper, aluminum overseal, and flip-off cap. The drug product will be reconstituted by a 
diluent consisting of sterile water in a prefilled syringe (PFS). The lyophilized drug product 
contains excipients that, after reconstitution, will yield a solution as detailed in the IB.
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The fill volume of the drug product vial and diluent PFS are designed such that the intended 
vaccine dose is delivered by injecting the entire contents of the syringe.
6.1.2. Placebo
Placebo will be a lyophile match to the vaccine, which will consist of excipients matched to 
those used in the RSVpreF vaccine formulation, minus the active ingredients. 
The physical appearance of the reconstituted RSVpreF and placebo will be matched, and the 
study will be conducted in a double-blinded manner.
The fill volume of the placebo vial and diluent PFS is designed such that the intended 
placebo dose is delivered by injecting the entire contents of the syringe.
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
6.1.3. Administration
Maternal participants will receive 1 dose of investigational product at the vaccination visit 
(Day 1) in accordance with the study’s SoA.  The investigational product will be 
administered intramuscularly by injecting the entire contents of the syringe into the deltoid 
muscle, preferably of the nondominant arm, unless medically contraindicated, in which case 
the injection may be administered in the dominant arm. Investigational product
administration will be performed by appropriately designated study staff at the investigator 
site.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance. 
Investigational product administration details will be recorded on the case report form (CRF).
6.1.4. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluent for the 
investigational product (RSV vaccine or placebo). The investigational product supplies are 
provided in a kit that contains the investigational product (RSV vaccine or placebo 
lyophilized powder in a vial), a prefilled syringe containing sterile water, and a vial adapter.
Instructions for medical device use are provided in the investigational product manual 
(IP manual).
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Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the study personnel throughout the study.
Please refer to Section 8.3.9 for details. 
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention, as applicable for 
temperature-monitored shipments. 
2. Only maternal participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking days must indicate the minimum and maximum 
temperature since previously documented for all site storage locations upon return to 
business.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  All study interventions will be 
accounted for using an investigational product accountability form/record.
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
6. Study interventions should be stored in their original containers and in accordance with 
the labels.
7. See the IP manual for storage conditions of the study intervention once reconstituted.
8. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use of 
the study intervention after the temperature excursion. Use of the study intervention prior 
to Pfizer approval will be considered a protocol deviation. Specific details regarding the 
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definition of an excursion and information the site should report for each excursion will 
be provided to the site in the IP manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
6.2.1. Preparation and Dispensing
Refer to the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
Investigational product and placebo will be prepared by qualified site personnel according to 
the IP manual.  The investigational product will be administered only to maternal participants 
who are blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Blinding of Study Site Personnel 
This study is a double-blinded study, as the physical appearance of RSVpreF and placebo 
will be matched. The maternal participant, her parent(s)/legal guardian (if a minor), 
investigator, study coordinator, and all site staff will be blinded.
Please refer to the IP manual for further details.
6.3.2. Blinding of the Sponsor
The sponsor study team members will be blinded throughout the study to the vaccine 
assignments of all participants enrolled in the study. 
Laboratory personnel performing the serology and virology assays will remain blinded to 
vaccine assigned/received throughout the study.
6.3.3. Allocation to Investigational Product
Allocation (randomization) of maternal participants to vaccine groups will proceed through 
the use of an interactive response technology (IRT) system (interactive Web-based response 
[IWR]).  The site personnel (study coordinator or specified designee) will be required to 
enter or select information including but not limited to the user’s identification (ID) and 
password, the protocol number, and the maternal participant number.  The site personnel will 
then be provided with a vaccine assignment, randomization number, and dispensable unit 
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(DU) or container number as investigational product is being supplied via the IRT system.  
The IRT system will provide a confirmation report containing the maternal participant 
number, randomization number, and DU or container number assigned. The confirmation 
report must be stored in the site’s files. 
Note: Maternal participants will be randomized to a vaccine group as described above.  The 
infants of the maternal participants will be manually assigned an infant participant number at 
birth.
Investigational product will be dispensed and administered at study Visit 1 summarized in 
the SoA. 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Maternal participants will be assigned to receive investigational product according to the 
randomization scheme.  Investigators will remain blinded to the investigational product 
assigned to each maternal participant throughout the course of the study.
6.3.4. Breaking the Blind 
The study will be maternal participant and investigator blinded.
At the initiation of the study, the investigator will be instructed on the method for breaking
the blind for an individual participant.  The method will be an electronic process.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the participant.  The 
investigators should make every attempt to contact a member of the sponsor’s study team 
prior to breaking the blind.  When the blinding code is broken, the reason must be fully
documented and entered on the CRF.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy 
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal Participants

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study. Note: COVID-19 vaccines authorized for temporary or emergency use will not be 
prohibited during the course of this study.
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
Receipt of blood/plasma products or Ig, from 60 days before investigational product 
administration, or planned receipt through delivery, with 1 exception, Rho(D) immune 
globulin (eg, RhoGAM), which can be given at any time.

Immunosuppressive therapy is prohibited during the course of the study.

Nonstudy vaccines may not be given concomitantly with the investigational product or 
within 7 days after investigational product administration (Day 1 to Day 7), except if 
medically necessary (eg, during an outbreak or pandemic situation).

Note: Licensed Tdap, may not be coadministered with the investigational product or 
given within 14 days after investigational product administration (Day 1 to Day 14), 
except if medically necessary (eg, during an outbreak- or pandemic-related situation).
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal Participants

Licensed vaccines (including influenza vaccine, tetanus toxoid, tetanus diphtheria 
vaccines, licensed COVID-19 vaccines, and COVID-19 vaccines authorized for 
temporary or emergency use) may be given during the study starting 7 days after
investigational product administration (Day 8), with the exception of licensed Tdap,
which may be given starting 14 days after investigational product administration (Day 
15) as detailed in Section 6.5.1.

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. Short-term systemic corticosteroid (equivalent of <20 mg/day of prednisone)
use for ≤14 days prior to the administration of investigational product is permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during participant participation in the 
study.
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following vaccinations and treatments for maternal participants would require reporting 
in the CRF during the study: 

Details of any vaccinations given at any time during the pregnancy through the final 
study visit will be collected and recorded in the CRF.

Details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given to the maternal participant at any time during the 
pregnancy or during the study will be collected and recorded in the CRF.

Any prescribed medications taken to treat medically attended respiratory illnesses from 
enrollment until the final study visit will be recorded in the CRF.
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Concomitant medications not meeting the criteria above will be assessed but not documented 
on the CRF.
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant Participants

Investigational vaccines, drugs, nutritional products, or medical devices are prohibited 
during the course of the study.
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant Participants

ONLY routine treatments, routine vaccinations, and routine procedures 
(eg, circumcision) are permitted at any time during the study, in accordance with national 
recommendations, medical standard of care, or accepted practice.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during infant participant participation in the study.

Local anesthetic may be applied to the site of the blood draw, as appropriate.
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications – Infant 
Participants
The following CRF reporting guidelines are applicable to treatments given to infant 
participants during the study:

Details of any Ig (including monoclonal antibodies [eg, Synagis] or immune globulin 
[eg, hepatitis B immune globulin (HBIG)]) or blood products (eg, whole blood, packed 
cells) given to the infant participant will be collected from the time of birth until the final 
study visit and recorded in the CRF.

Any prescribed medication taken to treat medically attended respiratory illnesses from 
the time of birth until the final visit.

Details of IV fluids given during an MA-RTI will be collected and recorded in the CRF.
6.6. Dose Modification
Dose modification is not applicable in this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Discontinuation of study intervention is not applicable in this study.
7.2. Participant Discontinuation/Withdrawal From the Study
A maternal participant may withdraw from the study at any time at her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. An infant participant may withdraw from the study at 
any time at the request of his or her parent(s) and/or legal guardian(s) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.
The participants, or, if appropriate, their parent(s) and/or legal guardian(s), should be
questioned regarding their reason for withdrawal. The participant will be permanently
discontinued from the study at that time.
If a maternal participant withdraws from the study, she may request destruction of any 
remaining samples taken and not tested, but data already generated from the samples will 
continue to be available and may be used to protect the integrity of existing analyses. If an 
infant participant is withdrawn from the study, his or her parent(s) and/or legal guardian(s) 
may request destruction of any remaining samples, but data already generated from the 
samples will continue to be available, and may be used to protect the integrity of existing 
analyses. The investigator must document any such requests in the site study records and 
notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
Participants who withdraw after randomization will not be replaced.
7.3. Withdrawal of Consent
Maternal participants and parent(s)/legal guardian(s) of infant participants born to maternal 
participants who request to withdraw consent from any further study contact or with persons 
previously authorized by the participant to provide this information should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible.  The withdrawal of consent should be explained in detail in the medical records by 
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the investigator, as to whether the withdrawal is only from study procedures and/or 
postvaccination study follow-up. If the participant (maternal or infant) only withdraws from 
a study procedure, safety information should be completed until the end of the study, unless 
consent for further contact has been withdrawn.  In the event that vital status (whether the 
participant is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
The regulatory and ethical considerations for this study, including the informed consent 
process, are summarized in Section 10.1.1 and Section 10.1.3.
7.4. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant, or parent(s) and/or legal guardian(s), and 
reschedule the missed visit as soon as possible and counsel the participant or parent(s) 
and/or legal guardian(s) on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or parent(s) and/or legal guardian(s) wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record.

Should the participant or parent(s) and/or legal guardian(s) continue to be 
unreachable, the participant will be considered to have withdrawn from the study.
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
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Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the maternal participant’s routine clinical 
management and obtained before signing of the ICD may be utilized for baseline 
purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA and protocol.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
8.1. Efficacy Assessments
8.1.1. Efficacy Assessments – Infant Participants
MA-RTIs in the infant participant will be identified from 72 hours after the infant’s delivery 
until the end of the infant’s participation in the study.  If the infant participant meets any RTI 
criteria listed below that require a visit by or a visit to an HCP (outpatient or inpatient visit, 
emergency room, urgent care, or scheduled home visit), an RTI study visit by the study staff 
will be required (see Section 8.11.7).
The RTI criteria are if the infant experiences 1 or more of the following respiratory signs or 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any duration

Cough

Inability to feed for any duration due to respiratory symptoms
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
Apnea

Any other respiratory symptom of concern 
Evaluation of these MA-RTI events will be based on predefined clinical signs and symptoms 
and testing criteria (shown in Table 1) obtained at the medically attended visit with the 
healthcare provider and/or the study visit. These events will be assessed and confirmed to be 
contributing to the study endpoints by an independent EAC as per the protocol.
8.1.1.1. Midturbinate Nasal Swab Collection and Testing Requirements for Endpoint 
Confirmation – Infant Participants
Midturbinate nasal swabs will be collected for RSV analyses from infant participants at each 
RTI study visit during the RSV surveillance period from birth until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). The swabs
will be sent to Pfizer for centralized reverse transcription–polymerase chain reaction 
(RT-PCR) testing.
RSV testing performed locally as part of routine care will be considered valid when analyzed 
under the following conditions:  

Nucleic acid amplification technology (NAAT)-based test result positive for RSV was 
obtained using a Food and Drug Administration (FDA)-cleared assay.

AND

NAAT-based test result was obtained in a laboratory that is currently Clinical Laboratory 
Improvement Amendments (CLIA)-certified or has the equivalent US 
certification/accreditation (eg, College of American Pathologists [CAP]) or the equivalent 
ex-US certification as outlined in the adjudication charter. 
Note: Rapid antigen-based test results will not be considered for endpoint assessment.
Study samples should be collected as close to the medical visit as possible and preferably 
within 72 hours of the MA-RTI visit. Study samples positive for RSV by RT-PCR as 
defined above will count toward the endpoint definition when collected for up to 10 days 
after the MA-RTI, where Day 1 is the day of the MA-RTI visit. These results will be used 
for MA-RTI endpoint definition and confirmation as detailed in Table 1.
8.1.1.2. Events for Adjudication and Submission Guidance – Infant Participants
To maintain scientific integrity, this protocol will use an EAC for the adjudication of all 
efficacy endpoints as summarized below.  The EAC will remain blinded to the maternal 
participants’ vaccine assignments, and the EAC’s assessment of these events will represent 
the final confirmed endpoint classification of the event. 
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The efficacy-related events for adjudication include all MA-RTI events. The study 
definitions for endpoint events and the MA-RTI adjudication criteria for the EAC, including 
roles and responsibilities, are specified in the endpoint adjudication committee charter 
(EACC). 
The identification of an MA-RTI will be made by the investigational site and communicated 
to Pfizer or its designee. However, these MA-RTI events may also be identified by Pfizer or 
its designee during the review of clinical data listings or by site monitors during routine 
monitoring of the infant participants’ study records. Pfizer or its designee will notify the 
investigational site of any events identified during this process.
The EAC is responsible for adjudicating whether MA-RTI events fulfill the protocol-defined 
clinical criteria as a primary endpoint, whether the event was due to RSV based on 
confirmatory testing, and the severity of the illness (eg, MA-RTI, MA-LRTI, or severe 
MA-LRTI).  The EAC will adjudicate all RSV-positive MA-RTI cases through the active 
follow-up period including all cases occurring up to 180 days after birth. The EAC will 
adjudicate severe manifestations of RSV: all RSV-associated cases of hospitalization and 
severe MA-LRTI. All deaths during the study are to be reported to Pfizer Safety upon 
awareness. 
The Pfizer study team or designee will provide a listing of specific documents needed to 
support endpoint adjudication by the EAC. These documents will be detailed in the EACC
and the ISF.  Obtaining and submitting the documentation, including results of local testing 
for RSV, will be the responsibility of the investigational site. Documentation will vary based 
on the potential endpoint requiring adjudication and may include (but not be limited to) 
emergency room visit records, hospital discharge summaries, clinic and/or progress notes, 
diagnostic tests, pathology reports, autopsy reports, and death certificate information, as 
applicable.
Pfizer may request that additional cases of interest be reported to the committee in addition to 
those listed above, including cases in which RSV testing is indeterminant or otherwise 
unclear. Cases that are determined to be RSV positive using non–NAAT-based clinical 
testing can be adjudicated, explored, and summarized descriptively.
8.1.2. Exploratory Efficacy Assessments – Maternal Participants
An MA-RTI will be identified from vaccination until the end of the study and will contribute 
to an exploratory endpoint for maternal participants.  The definition and assessment criteria 
as described in Section 8.10.6 include a visit by or to a healthcare provider (outpatient or 
inpatient visit, emergency room, urgent care, or home visit) for any symptoms in the RTI 
criteria as detailed in Table 2.
The maternal participant or her parent(s)/legal guardian (if a minor) should contact the study 
staff immediately but no later than the next scheduled visit to report RTI signs and symptoms 
for which she sought medical attention. The procedures as detailed in Section 1.2.3.1 and 
Section 8.10.6 will be required to capture the event in the CRF.
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8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal and Infant 
Participants
Infant MA-RTI events that are consistent with the clinical and endpoint definitions for infant 
participants should not be recorded as AEs. These data will be captured as efficacy 
assessment data only, as these are expected endpoints.
For maternal participants, MA-RTI events that are consistent with the clinical and endpoint 
definition will be captured as detailed in Section 8.1.2 and will not be recorded as AEs.
Any event that the investigator has judged to have a causal relationship with the 
investigational product or to have resulted in death MUST be reported to Pfizer Safety as 
described in Appendix 2, even if that event is a component of an endpoint.
8.1.4. Immunogenicity Assessments
8.1.4.1. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be approximately 30 mL (~15 mL/visit).
8.1.4.2. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical 
Consideration for Clinical Trials Performed in Children.36
All infants will have a cord blood sample collected at birth. The cord blood is collected from 
the umbilical cord vein attached to the placenta after the umbilical cord has been clamped 
and cut. Blood should be collected as soon as feasible after birth to minimize coagulation 
and maximize volume. The total volume of cord blood to be collected for antibody 
assessment in this study will be 10 mL. 
If cord blood is unavailable, a blood sample may be collected from the infant participant up 
to 7 days after birth but preferably within 24 hours after birth.  The infant’s weight must 
be used to determine the volume of blood that can be collected (see Table 3).
A blood sample will be collected from the infant participant only if a cord sample is not
obtained. In the event that a sample is collected, the volume of blood will vary depending on 
the infant’s weight. 
The maximum volume of blood collected from the infant in the absence of cord blood will be 
no more than 5 mL.
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Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained
Body Weight (in kg)
Approximate Volume of Blood (in mL) 
to Be Collected 
<1.3
No blood draw
1.3 to ≤2.4
1.0
>2.4 to ≤3.7
2.0
>3.7 to ≤4.9
3.0
>4.9 to ≤6.2
4.0
>6.2
5.0
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant Participants
Maternal sera (prevaccination/time of delivery) and infant cord blood collected will be 
assayed for RSV A and RSV B serum neutralizing titers and anti-RSV prefusion F IgG 
levels. Maternal sera collected may be tested for Ig levels against nonvaccine RSV antigens
to assess natural RSV exposure.
RSV A and RSV B serum neutralizing titers will be determined and reported as the 
neutralizing titer. IgG levels will be determined against both RSV A and RSV B prefusion F 
antigens in a direct-binding Luminex immunoassay (dLIA) and reported as an anti–
prefusion F IgG level.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development – Maternal and Infant Participants
Samples remaining after completion of the planned assays from blood draws or infant 
respiratory nasal swab specimens taken throughout the study may be used for additional 
vaccine and infectious disease related research. Samples may also be used for assay 
development, standardization, qualification, and validation.  This work is critical in the 
development, qualification, and validation of serological assays and is required by regulatory 
authorities for their use in the licensure of a vaccine.
8.1.4.5. Respiratory Pathogens – Infant Participants
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI
visit during the RSV surveillance period from birth until Visit 3, and for all hospitalizations 
due to an RTI and severe cases of MA-LRTI during the RTI surveillance period from 
Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). 
Samples will be analyzed for RSV A, RSV B, and other respiratory pathogens by polymerase 
chain reaction (PCR)-based assays at a central laboratory. Additional exploratory analyses 
may also be performed.
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Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.6. Biological Samples – Maternal and Infant Participants
Samples will be used only for scientific research.  Each sample will be labeled with a code so 
that the laboratory personnel testing the samples will not know the maternal or infant
participant’s identity.  Samples that remain after performing assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.  If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No sequencing of the maternal or infant participant’s DNA will be performed. 
The maternal participant may request that her (or her infant’s) samples, if still identifiable, be 
destroyed at any time; however, any data already collected from those samples will still be 
used for this research.  The biological samples may be shared with other researchers as long 
as confidentiality is maintained, and no testing of the maternal and infant participant’s DNA 
is performed.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
Safety parameters will be assessed as described in the SoA and below for both maternal and 
infant participants.
8.2.1. Participant Electronic Diary – Maternal Participants
All maternal participants vaccinated in the study will be observed for at least 30 minutes after 
investigational product administration for any acute reactions. For all maternal participants, 
prespecified local reactions and systemic events will be collected for 7 days after vaccination.
Maternal participants will be required to use an electronic diary (e-diary), installed on a 
provisioned device or as an application on a personal device, and will be asked to monitor 
and record local reactions, systemic events, and temperature each evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  Prior 
to vaccination, a baseline assessment of prespecified systemic events will be recorded in the 
e-diary.
The e-diary allows recording of these assessments only within a fixed time window each day, 
thus providing the accurate representation of the maternal participant’s experience at that 
time.
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If the maternal participant is illiterate, a study staff/field worker may visit the maternal 
participant in her home or contact her via phone daily after vaccination to assess and record 
local reactions, systemic events, and temperature each day (beginning in the morning) for 
6 days following vaccination (Day 2 through Day 7). Maternal participants or her 
parent(s)/legal guardian (if a minor) may call the site and report additional local reactions and 
systemic events at any time during the Day 1 to Day 7 reporting period.  The study staff/field 
worker will be required to record these data on a provisioned device or an application on a 
personal device, thus providing the accurate representation of the maternal participant’s 
experience at that time.  For events persisting at Day 7 and use of antipyretic medication 
continuing at Day 7, the field worker will continue to visit the participant and record 
information until resolution.
Data on local reactions, systemic events, and temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via an internet-based 
portal.  At intervals agreed to by the vendor and Pfizer, these data will be transferred 
electronically to Pfizer for analysis and reporting.  These data do not need to be recorded by 
the investigator in the CRF, except the following conditions:

If a maternal participant withdraws because of prompted events recorded in the e-diary, 
the event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF. 
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate maternal participant compliance and as part of the 
ongoing safety review. These prospectively collected occurrences of local reactions and 
systemic events are graded as described in Section 8.2.1.1 and Section 8.2.1.2.
8.2.1.1. Local Reactions – Maternal Participants
Following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), the 
maternal participants or her parent(s)/legal guardian (if a minor)/study staff member/field 
worker will be asked to assess redness, swelling, and pain at the injection site and to record 
the symptoms in the e-diary or appropriate device, in the evening or daily based on local 
practice.
Redness and swelling will be measured by the maternal participant/study staff/field worker 
and recorded in measuring device units (range: 1 to 20 and 21+) and then categorized during 
analysis as mild, moderate, or severe based on the grading scale in Table 4. Measuring 
device units can be converted to centimeters according to the following scale: 1 measuring 
device unit = 0.5 cm.
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A maternal participant with severe redness, swelling, or pain at the injection site will be 
prompted to contact the investigator to perform an unscheduled visit to assess the reaction or 
will be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate.  In the event that the maternal participant
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor).
Only an investigator or a qualified designee is able to classify a maternal participant’s local 
reaction as Grade 4, after clinical evaluation of the maternal participant or documentation 
from another medically qualified source (eg, emergency room or hospital record) or, in the 
case of pain at the injection site only, contact with the maternal participant.  If a maternal 
participant experiences a Grade 4 local reaction, the investigator must immediately notify the 
sponsor.  A Grade 4 reaction will be collected as an AE on the CRF.  The event will be 
graded using the AE intensity grading scale (Section 10.2.4).
The site staff/field worker will educate the maternal participant and her parent(s)/legal 
guardian (if a minor) regarding signs and symptoms that would prompt site contact.
If a local reaction persists beyond the end of the e-diary period, the maternal participant or 
her parent(s)/legal guardian (if a minor) will be requested to report that information and/or 
any new AEs that develop to the investigator, or the study staff/field worker will continue to 
call or visit the maternal participant to assess and record the information until resolution, as 
per local practice. The investigator will enter this additional information in the maternal 
participant’s source notes and CRF.
Table 4.
Grading Scale for Local Reactions
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis
Pain (at the 
injection site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a maternal participant’s local reaction as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
contact with the maternal participant or her parent(s)/legal guardian (if a minor).  Grade 4 local reactions 
will be collected on the AE case report form and assessed by the investigator using the AE intensity 
grading scale as detailed in Section 10.2.4.
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8.2.1.2. Systemic Events – Maternal Participants
Prior to vaccination on Day 1, a baseline assessment of fatigue, headache, vomiting, 
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e-diary. Following 
vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), maternal 
participants or their parent(s)/legal guardian (if a minor) will be asked to assess fatigue, 
headache, vomiting, nausea, diarrhea, muscle pain, and joint pain and to record the symptoms 
in the e-diary in the evening or, based on local practice in certain countries/locales, a study 
staff member/field worker will call or visit maternal participants daily after vaccination to 
assess the presence of systemic events each day (beginning in the morning) for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  The 
study staff member/field worker will record the symptoms in the e-diary daily. The 
symptoms will be assessed by the maternal participant according to the grading scale in 
Table 5.  Maternal participants and their parent(s)/legal guardian (if a minor) will also be 
instructed to contact site staff if they visit the emergency room or are hospitalized for severe 
fatigue, headache, vomiting, nausea, diarrhea, muscle pain, or joint pain within 7 days after 
vaccination. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor). The study staff/field worker may also contact the 
maternal participant or her parent(s)/legal guardian (if a minor) to obtain additional 
information on events entered into the e-diary.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic 
event as Grade 4, after clinical evaluation of the maternal participant or documentation from 
another medically qualified source (eg, emergency room or hospital record) or contact with 
the maternal participant.  If a maternal participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.  Grade 4 reactions will be collected as an 
AE on the CRF.  The event will be graded using the AE intensity grading scale 
(Section 10.2.4).
Further, if a systemic event persists beyond the end of the e-diary period, the maternal 
participant or her parent(s)/legal guardian (if a minor) will be requested to report that 
information and/or any new AEs that develop to the investigator, or the study staff/field 
worker will continue to call or visit the maternal participant to assess and record the 
information until resolution, as per local practice. The investigator will enter this additional 
information in the maternal participant’s source notes and CRF.
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Table 5.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness in 
diaries)
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Headache
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Vomiting
1 to 2 times in 24 hours
>2 times 
in 24 hours
Requires 
intravenous 
hydration
Emergency room 
visit 
or hospitalization 
for severe vomiting
Nausea
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe nausea
Diarrhea
2 to 3 loose stools
in 24 hours
4 to 5 loose stools
in 24 hours
6 or more loose 
stools
in 24 hours
Emergency room 
visit
or hospitalization 
for severe diarrhea
Muscle pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe muscle pain
Joint pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe joint pain
a.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic event as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the maternal participant or her 
parent(s)/legal guardian (if a minor).  Grade 4 systemic reactions will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.1.3. Temperature – Maternal Participants
A digital thermometer will be given to the maternal participant with instructions on how to 
measure oral temperature at home in degrees Celsius.  Temperature will be collected in the 
evening for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination) and at any time during the 7 days following vaccination that fever is suspected. 
Similarly, based on local practice in certain countries/locales, the study staff/field worker will 
call or visit maternal participants daily for 6 days after vaccination (Day 2 through Day 7, 
where Day 1 is the day of vaccination) to collect the temperature.
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Fever is defined as an oral temperature of ≥38.0°C (≥100.4°F). The highest temperature for 
each day will be recorded in the e-diary, where possible. In certain countries/locales, if a 
temperature of ≥38.0°C (≥100.4°F) is recorded for a maternal participant during the 
collection of diary events after vaccination, the study staff/field worker will perform a rapid 
test for malaria as per local practice.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature less than 38.0°C [100.4°F]) in order to 
collect a stop date in the CRF. 
A maternal participant with a fever >38.9°C (>102.0°F) will be prompted to contact the 
investigator. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as applicable. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant or 
her parent(s)/legal guardian (if a minor).  The investigator or qualified designee will assess 
the fever and perform an unscheduled visit as appropriate.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as 
Grade 4, after clinical evaluation of the maternal participant, documentation from another 
medically qualified source (eg, emergency room or hospital record), or contact with the 
maternal participant or her parent(s)/legal guardian (if a minor).  Grade 4 fevers will be 
collected on the AE CRF and assessed by the investigator using the AE intensity grading 
scale as detailed in Section 10.2.4.
Temperature will be measured and recorded to 1 decimal place and then categorized during 
analysis as mild, moderate, or severe based on the intensity grading scale provided in
Table 6.
Table 6.
Ranges for Fever
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fever
≥38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°C
a.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as Grade 4, 
after clinical evaluation of the maternal participant, documentation from another medically qualified 
source (eg, emergency room or hospital record), or contact with the maternal participant or her 
parent(s)/legal guardian (if a minor).  Grade 4 fevers will be collected on the AE case report form and 
assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant Participants
There are no protocol-required laboratory assessments.
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8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 4.  Device deficiencies are covered in Section 8.3.9.
AEs will be reported by the maternal participant/parent(s)/legal guardian(s).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7).
Each maternal participant or her parent(s)/legal guardian (if a minor) and parent/legal 
guardian/legally authorized representative of an infant participant will be questioned about 
the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
Maternal Participants
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each maternal participant including her fetus begins from the time the maternal 
participant and her parent(s)/legal guardian (if a minor) provides informed consent, which is 
obtained before participation in the study (ie, before undergoing any study-related procedure 
and/or receiving investigational product), through and including a minimum of 28 calendar 
days after the last administration of the investigational product.
In this study, the investigator and site staff will ensure the active elicitation and collection of 
safety events as detailed below:

The active collection period for nonserious AEs begins once informed consent has been 
provided and continues through a minimum of 28 calendar days after vaccination.

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

In addition, AEs occurring up to 48 hours after blood draws that are related to study 
procedures must be reported in the CRF.
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
Details of any MA-RTI will not be collected as AEs/SAEs from informed consent until 
the maternal participant completes the study, unless the investigator or an appropriate 
designee deems the event to be possibly related to the investigational product or to have
resulted in death as detailed in Section 8.1.2 and Section 8.1.3.
For maternal participants who are screen failures, the active collection period ends when 
screen failure status is determined.
Infant Participants
For the infant participant, the time period for actively eliciting and collecting safety events is 
detailed below:

The active collection period for nonserious AEs begins at birth and continues through and 
including a minimum of 28 calendar days after birth. 

The active collection period for NDCMCs and SAEs begins at birth and continues 
through the last study visit. 
o
Details of any MA-RTI will not be collected as AEs/SAEs from 72 hours after 
birth until the infant participant completes the study, unless the investigator or an 
appropriate designee deems the event to be possibly related to the investigational 
product or if the event resulted in death. See Section 8.1 for the reporting 
procedures for efficacy-related endpoints. Note: Details of the MA-RTI visit 
should be recorded in the eCRF.

In addition, AEs occurring up to 48 hours after blood draws or nasal swabs that are 
related to study procedures must be reported in the CRF.
For Both Maternal and Infant Participants
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For maternal participants, and parent(s)/legal guardian(s) of infant participants born to 
maternal participants, who withdraw from the study and withdraw consent for the collection 
of future information, the active collection period ends when consent is withdrawn. 
If a participant definitively discontinues or temporarily discontinues study intervention
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form.
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Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the Vaccine SAE Reporting Form. 
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the Vaccine SAE Reporting Form, immediately upon awareness and under no 
circumstances should this exceed 24 hours.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy; 
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those that occur within 1 month after birth; or congenital 
anomaly* [in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal 
death]), the investigator should follow the procedures for reporting SAEs.  In addition, infant 
deaths after 1 month of age should be reported as SAEs.
Further follow-up may be requested by the sponsor and will be handled on a case-by-case 
basis (eg, follow-up on preterm infants to identify developmental delays).
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety. 
The same is applied for those SAEs after the active collection period has ended, should they 
occur to the fetus.  In addition, infant deaths that occur after 12 months of age should be 
reported as SAEs when the investigator believes the SAE or death has at least a reasonable 
possibility of being related to investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.37
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All AEs/SAEs occurring in a participant during the active collection period, which begins 
after obtaining informed consent as described in Section 8.3.1, will be recorded on the AE 
section of the CRF.
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The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant or her parent(s)/legal guardian (if a minor) and
parent(s)/legal guardian(s) of infant participants born to maternal participants.
The investigator obtains general information on the pregnancy and its outcome for all study 
participants.  The investigator will follow the pregnancy until completion (or until pregnancy 
termination).  In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth.  In the event of a termination, the reason(s) for termination should be 
specified and, if clinically possible, the structural integrity of the terminated fetus should be 
assessed by gross visual inspection (unless preprocedure test findings are conclusive for a 
congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, stillbirth, neonatal death,
defined as those deaths that occur within 1 month after birth; or congenital anomaly* [in a 
live-born baby, a stillbirth, or a neonatal death]), the investigator should record this 
information in the CRF.  In addition, infant deaths after 1 month of age should be recorded in 
the CRF as SAEs. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.37
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.4).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 2.
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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
Potential efficacy endpoints on this study as defined in Section 8.1 will be excluded from the 
standard SAE reporting process unless deemed possibly related to investigational product.
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the 
Investigational Product
8.3.5.1. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Scenarios of exposure during breastfeeding for infants not delivered during the study must be 
reported, irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours 
of the investigator’s awareness, using the Vaccine SAE Reporting Form.  An 
exposure-during-breastfeeding report is not created when a Pfizer drug specifically approved 
for use in breastfeeding women (eg, vitamins) is administered in accord with authorized use.  
However, if the infant experiences an SAE associated with such a drug’s administration, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.2. Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
investigational product, which may or may not lead to the occurrence of an AE. Such 
persons may include HCPs, family members, and other roles that are involved in the trial 
participant’s care.
Note: This does NOT apply to maternal participants enrolled in this trial.
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In addition, the scenarios below describe environmental exposures that could lead to an 
exposure during pregnancy (EDP): 

A female becomes or is found to be pregnant, having been exposed (eg, because of 
environmental exposure) to the investigational product; or the female becomes or is 
found to be pregnant after being exposed to the investigational product;

A male has been exposed (eg, because of environmental exposure) to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy. 
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the Vaccine SAE Reporting Form and the Exposure During Pregnancy 
Supplemental Form, as applicable, regardless of whether there is an associated SAE.  In the 
event of an EDP, the information submitted should include the anticipated date of delivery.  
Since the information does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the ISF.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
are as follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.
8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
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8.3.8. Adverse Events of Special Interest
This section provides information on adverse events of special interest (AESIs) that may be 
detected during the study.
For infant participants:38

Preterm birth (born at <37 weeks’ gestation)

Birth weight 1001 to 2500 g

Developmental delay*

Positive viral (PCR or antigen-based) testing for SARS-CoV-2, when not reported 
during a MA-RTI visit, should be reported as SARS-CoV-2 test positive
The following AESIs are to be reported as SAEs:

Extremely preterm birth (<28 weeks)

Extremely low birth weight (≤1000 g)
For maternal participants:

Preterm delivery

Positive viral (PCR or antigen-based) testing for SARS-CoV-2, when not reported 
during a MA-RTI visit, should be reported as SARS-CoV-2 test positive
All AESIs must be reported as an AE or SAE following the procedures described in
Section 8.3.1 through Section 8.3.4 except the active collection period for AESIs is from the 
signing of the ICD until the end of the study for maternal participants and from birth until the 
end of the study for infant participants.
Notes: An AESI that is recorded as an SAE must be reported using the Vaccine SAE 
Reporting Form.
* Developmental delay is to be assessed by clinical expertise using local guidelines for 
standard of care. Events identified as both an AESI and an NDCMC should be reported as an 
AESI in the CRF.
8.3.8.1. Lack of Efficacy
This section is not applicable for this study, as efficacy is yet to be demonstrated in the study 
population.
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8.3.9. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 4.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 2 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 4.
8.3.9.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  Follow-up applies to all participants, including 
those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
Information will be provided to the sponsor as described in the IP manual. 
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
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8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration by an incorrect route;

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
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In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any additional dose of investigational product will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose in the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
No interruptions or dose modifications will be made in this study. 
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
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8.9. Health Economics
Health economics will be evaluated in exploratory analyses assessing vaccine impact on 
healthcare resource utilization parameters evaluated during study visits, which may include 
the following: number and type of medical visits, length of hospital stay, requirement for 
mechanical ventilation, requirement for respiratory diagnostic procedures, requirement for IV 
fluids, requirement for prescriptions, and antibiotic use. 
8.10. Procedures – Maternal Participants 
8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to Vaccination to Day 1 –
Visit 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant or their parent(s)/legal 
guardian (if a minor). Each signature on the ICD must be personally dated by the signatory.
Maternal participants who might be illiterate must thumbprint the ICD and it must be signed 
and dated by an impartial witness who was present throughout the entire informed consent 
process before performing any study-related procedures.
The investigator or his or her designee will also sign and date the ICD.  A copy of the 
signed/thumbprinted and dated ICD must be given to the maternal participant and her 
parent(s)/legal guardian (if a minor).  The source data must reflect that the informed 
consent was obtained before participation in the study.
If the maternal participant is found ineligible for the study based on a full assessment of 
inclusion and exclusion criteria, the investigator may advise the participant and her 
parent(s)/legal guardian (if a minor), either by telephone or face to face, that the participant 
will be excluded from further participation in the study, as defined in Section 5.4.  All 
eligible maternal participants will proceed to complete the vaccination visit.
Standard-of-care procedures performed prior to informed consent can be considered for use 
in the study provided they follow guidance around the timing of procedures stipulated in the 
protocol.
In countries/locales where procedures to confirm maternal participant eligibility for
this clinical trial are not routinely performed, the procedures must be obtained and 
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.
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The following procedures will be performed:

Obtain written informed consent, and assent if appropriate, from the maternal participant
before performing any study-specific procedures. If the maternal participant is illiterate,
she must thumbprint the ICD and it must be signed and dated by an impartial witness 
who was present throughout the entire informed consent process.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity).  The date of birth will be 
collected to critically evaluate the immune response and safety profile by age.

Obtain and record current/former alcohol, tobacco, marijuana, or any illicit drug usage.

Obtain and record any medical, surgical, and obstetric history of clinical significance 
including history from prior and current pregnancy(ies).

Record the LMP and estimated delivery date (EDD).

Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.

Record the prepregnancy BMI in the source documentation. If the prepregnancy BMI is 
not available, record the BMI at the time of the first obstetric visit during the current 
pregnancy. 

Perform targeted physical examination evaluating/noting any clinically significant 
abnormalities within the following body systems: 
o
Mandatory - general appearance; heart; lungs; abdomen.
o
Discretionary - skin; head, eyes, ears, nose, and throat; musculoskeletal; 
extremities; neurological; lymph nodes.  
Note: Significant medical and surgical history and abnormal observations from 
the physical examination will be documented and recorded in the CRF.

Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement.
o
Where an obstetric ultrasound examination is not performed at ≥18 weeks of 
pregnancy as part of prenatal standard of care, perform an ultrasound examination.
o
Note: Physical or obstetric examinations performed as standard of care may be 
admissible if performed within 7 days prior to the vaccination visit.
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
Obtain details of any Ig (including monoclonal antibodies or immune globulin [Rho(D) 
immune globulin, eg, RhoGAM]) or blood products (eg, whole blood, packed cells) given 
at any time during the current pregnancy.

Obtain details of any nonstudy vaccinations given at any time during the current 
pregnancy.

Obtain details of syphilis, HIV, and HBV status.

Note: Only participants with a documented negative syphilis test result and negative 
HIV antibody and HBV surface antigen test results obtained during the current 
pregnancy are eligible for randomization. 

If not performed as standard of care, assessment should be performed as part of the 
study, locally, and vaccination of maternal participant should be deferred until the 
results are available and confirmed to be negative within 28 days prior to study 
randomization.

Ensure and document that all the inclusion criteria and none of the exclusion 
criteria are met.

Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.2.3.

Issue the maternal participant an e-diary and provide instructions on its completion
(if applicable). Note: eDiary completion instructions may be provided to her 
parent(s)/legal guardian (if a minor).

Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures, and provide instructions on their use to the maternal 
participant and her parent(s)/legal guardian (if a minor).

On the day of and prior to vaccination, ask the maternal participant to capture the 
baseline systemic event measurements in her e-diary or the site staff will capture the 
baseline systemic event measurements in the provisioned device (if applicable for 
illiterate participants).

Prior to vaccination, collect a blood sample of approximately 15 mL for serologic 
assessments (prevaccination blood collection should take place on the same day or within 
7 days before the vaccination visit).

Obtain the maternal participant’s randomization number and investigational product kit 
number using the IRT system. Refer to the IRT manual for further instructions on this 
process.
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
Qualified site staff member(s) will administer a single-vial dose of investigational 
product into the deltoid muscle of the (preferably) nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
Please refer to the IP manual for further instruction on this procedure.

Site staff must observe the maternal participant for any acute reactions for at least 
30 minutes after investigational product administration.

Record any acute reactions in the maternal participant’s source documents, on the AE 
page of the CRF, and on the Vaccine SAE Reporting Form as applicable.

Ask the maternal participant to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination, OR explain to the maternal participant that a study staff 
member/field worker will call or visit her every day from Day 2 to Day 7 after 
vaccination (where Day 1 is the day of vaccination) to collect or take her temperature and 
record systemic events, acute local reactions, and use of antipyretic medication in a diary
(if applicable).

Ask the maternal participant or her parent(s)/legal guardian (if a minor) to contact the site 
staff or investigator immediately if she experiences any of the following from Day 1 to 
Day 7 after vaccination to determine if an unscheduled reactogenicity visit is required as 
detailed in Section 8.10.5 OR inform the maternal participant or her parent(s)/legal 
guardian (if a minor) that if she experiences any of the following from Day 1 to Day 7 
after vaccination or is taking antipyretic medication at Day 7, then the study staff/field 
worker will continue to visit until resolution.  Furthermore, the maternal participant will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns as detailed in Section 8.10.5.

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring >20 measuring device units 
(greater than 10 cm).

Severe pain at the injection site.

Any severe systemic event.

Inform the maternal participants or her parent(s)/legal guardian (if a minor) that if a 
temperature of ≥38.0°C (≥100.4°F) is recorded during the collection of diary data, she 
will be required to have a rapid test for malaria as per local practice and details will be 
recorded in the diary (if applicable, based on local practice).

Remind maternal participants or her parent(s)/legal guardian (if a minor) that study staff 
may contact them to obtain additional information on events entered into the e-diary.
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
Remind maternal participants or their parent(s)/legal guardian (if a minor) to inform the 
study staff of any AEs and SAEs that occur for the duration of the trial as described in 
Section 8.2 and Section 10.2.

Remind the maternal participant or her parent(s)/legal guardian (if a minor) to bring the 
completed e-diary to the next visit (if applicable). 

Complete the source documents.

The investigator or an authorized designee completes the CRFs and the blinded 
dispenser/administrator completes the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.

Maternal participants or their parent(s)/legal guardian (if a minor) will be instructed to 
contact the site to report any significant illness (new or worsening), any medically 
attended respiratory events (eg, doctor’s visit, emergency room visit), or any 
hospitalization that occurs during the study period as detailed in Section 8.10.6.

Request the maternal participant and her parent(s)/legal guardian (if a minor) to contact 
the site if she goes into labor/is admitted to the maternal unit (The study staff/field worker 
will contact the maternal participant prior to the next study visit to remind her, if 
applicable).
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After Vaccination)
If delivery occurs before this visit, this visit will not be conducted.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

Review the participant’s e-diary data. Collect stop dates of any e-diary events ongoing 
on the last day that the e-diary was completed and record stop dates in the CRF.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.
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
Record AEs and SAEs as described in Section 8.2 and Section 10.2. Note: Active 
elicitation and collection of AEs and SAEs through 28 days after vaccination must occur 
even if delivery occurs within 28 days after vaccination.

The investigator or an authorized designee completes the CRF.

Maternal participants and their parent(s)/legal guardian (if a minor) will be instructed to 
contact the site to report any significant illness (new or worsening), any medically 
attended respiratory events (eg, doctor’s visit, emergency room visit), or any 
hospitalization that occurs during the study period as detailed in Section 8.10.6. 

Request the maternal participant and her parent(s)/legal guardian (if a minor) to contact 
the site if she goes into labor/is admitted to the maternal unit (The study staff/field worker 
will contact the maternal participant prior to the next study visit to remind her, if 
applicable).
8.10.3. Delivery (Maternity Unit)
The delivery visit spans the time from when a participant is admitted in labor through 
discharge following delivery of her infant. Protocol-specified procedures associated with 
this delivery visit may be done at any time during this period.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

If available, record the maternal participant’s group B streptococcal (GBS) status and if 
any medication was given for intrapartum antibiotic prophylaxis (IAP). Note: Positive 
GBS carriage should not be reported as an adverse event in the CRF if performed in the 
setting of routine prenatal care.

Record details of any nonstudy vaccinations given since the last visit.

Collect a blood sample of approximately 15 mL for serologic assessments.  Note: The 
maternal participant’s blood sample can be taken at any time during the delivery visit, 
preferably before delivery. In the event that the blood sample cannot be obtained 
before delivery, the sample should be collected as close to delivery as possible and at 
most 48 hours postpartum.
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments 
must also be collected.  Cord blood is collected from the umbilical cord vein attached to 
the placenta prior to the blood clotting within the cord and after the umbilical cord has 
been clamped and cut.  This sample should be labeled with the infant’s participant ID 
number.
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
Record pregnancy outcome information, including vital status of the infant (live, 
stillbirth, etc), mode of delivery (vaginal delivery or cesarean section), and the use of any 
assisted devices (forceps or vacuum).

Record details of any MA-RTI, including the diagnosis. 

Record AEs as described in Section 8.2 and Section 10.2.

Ask the maternal participants and her parent(s)/legal guardian (if a minor) to contact the 
site to report any significant illness (new or worsening), any medically attended 
respiratory events (eg, doctor’s visit, emergency room visit), or any hospitalization that 
occurs during the study period as detailed in Section 8.10.6.

Ask the maternal participant and her parent(s)/legal guardian (if a minor) to contact the 
site staff or investigator if her newborn infant meets the MA-RTI study criteria OR the 
study staff/field worker will contact the maternal participant/legal guardian(s) weekly to 
remind them to report any MA-RTI (if applicable).

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 210 Days After 
Delivery)

Obtain details of any postnatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [eg, HBIG]) or Rho(D) immune globulin [eg, RhoGAM]) or blood 
products (eg, whole blood, packed cells) given since the last visit.

Record details of any nonstudy vaccinations given since the last visit.

Record details of any MA-RTI, including the diagnosis.

Ask the maternal participant and her parent(s)/legal guardian (if a minor) to contact the 
site staff or investigator if her infant meets the MA-RTI study criteria OR the study 
staff/field worker will contact the maternal participant/legal guardian(s) weekly to remind 
them to report any MA-RTI, if applicable.

Record AEs as described in Section 8.2 and Section 10.2.

Complete the maternal participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.10.5. Unscheduled Reactogenicity Visits
If the maternal participant or her parent(s)/legal guardian (if a minor) reports 1 or more of the 
following, a contact must occur as soon as possible between the maternal participant and the 
investigator, or a medically qualified member of the study site staff, to assess if an 
unscheduled reactogenicity visit is required OR based on local practice in certain 
countries/locales, maternal participants will be referred to the appropriate healthcare facility 
at the discretion of the study staff/field worker if there are any concerns regarding 
reactogenicity events, including:

redness at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

swelling at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

severe injection site pain on the arm that the investigational product was 
administered, 

fever ≥39.0°C (≥102.1°F).
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The maternal participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or

The participant/study staff/field worker recorded an incorrect value in the e-diary 
(confirmation of an e-diary data entry error), or

The investigator or appropriate designee determines that the visit is not required.
This contact will be recorded in the maternal participant’s source notes and in the CRF.
Any ongoing reactions must be assessed at the next scheduled visit.
The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure oral temperature.

Measure the participant’s heart rate.

Measure the participant’s blood pressure (seated).
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
Measure the minimum and maximum diameters of redness (if present) on the arm in 
which the investigational product was administered.

Measure the minimum and maximum diameters of swelling (if present) on the arm in 
which the investigational product was administered.

Assess if necrosis is present at the injection site on the arm in which the investigational 
product was administered.

Assess if any exfoliative dermatitis is present.

Assess any injection site pain on the arm in which the investigational product was 
administered that is present in accordance with the reactogenicity grading scale provided 
in Section 8.2.1.1.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 8.2.1.2.

Ask the participant or her parent(s)/legal guardian (if a minor) if she attended an 
emergency room visit or was hospitalized.

For severe pain at the injection site resulting in an emergency room visit or 
hospitalization, severe systemic events associated with an emergency room visit or 
hospitalization, any necrosis on the arm in which the investigational product was 
administered, or exfoliative dermatitis, the investigator or qualified designee must assess 
these events in accordance with the intensity AE grading scale provided in
Section 8.2.1.1 and Section 8.2.1.2.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

Complete the participant’s source documents.

The investigator or an authorized designee will complete the CRFs.

The study staff/field worker may contact the participant to obtain additional information 
on events entered into the e-diary, as appropriate.
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8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria – Maternal 
Participants

Starting from Day 1 after vaccination (where Day 1 is the day of vaccination) until the 
end of the study, all maternal participants will be monitored for MA-RTIs as detailed in 
Section 1.2.3.1 and Section 8.1.2. Maternal participants or their parent(s)/legal guardian 
(if a minor) should notify the site and/field worker of the occurrence of any MA-RTIs 
immediately but no later than the next study visit. Note: Site contact may be by an 
electronic method of communication (including but not limited to electronic messaging, 
short message service [SMS], text, email), by phone call, or by face-to-face contact.

The definition of maternal RTI includes 1 or more of the following signs and/or 
symptoms:
o
New or increased sore throat
o
New or increased cough
o
New or increased nasal congestion
o
New or increased nasal discharge
o
New or increased wheezing
o
New or increased sputum production
o
New or increased shortness of breath

Record the details of any MA-RTI, including the diagnosis, the medically attended visit 
location (hospital, outpatient visit, emergency room, urgent care, or home visit), duration 
of hospitalization, intensive care unit (ICU) duration if applicable, prescribed medications 
for the MA-RTI, assessments including RSV test result (eg, NAAT, rapid antigen 
detection tests, or any other molecular diagnostic test), if available, and the final 
diagnosis.

Record the details of any nonstudy vaccinations.

Record AEs as described in Section 8.2 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.11. Procedures – Infant Participants
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After Birth)

Manually assign a single infant participant identifier. This will be assigned manually by 
the site using the following convention: the infant participant’s identifier will be the 
maternal participant’s IRT-generated numeric ID but with the fifth digit changed to a 2 
(eg, if the maternal participant is given number 10011001, then the infant will be 
10012001).

Collect a cord blood sample of approximately 10 mL for immunogenicity assessments.  
Cord blood is collected from the umbilical cord vein attached to the placenta prior to the 
blood clotting within the cord and after the umbilical cord has been clamped and cut.  
This sample should be labeled with the infant’s participant ID number.

If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 24 hours, but up to 7 days after birth.  The volume of blood collected 
will be based on the weight of the infant (refer to Table 3).

Ensure and document that all the infant inclusion criteria and none of the infant exclusion 
criteria are met.

Collect demography (including complete date of birth [ie, dd-Mmm-YYYY], sex, race, 
and ethnicity).  The date of birth will be collected to critically evaluate the immune 
response.

Obtain and record the infant’s length, head circumference, and weight at birth.

Obtain and record the infant’s birth data, including GA and appearance, pulse, 
grimace, activity, and respiration (Apgar) score. 

Obtain and record background factors as described in Section 10.5.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.

Standard-of-care vital signs and examination procedures can be considered for use in 
the study provided they were performed within 72 hours after birth. Note: Please 
reference the physical examination procedures below for details. 

Perform a physical examination, if not performed as part of standard of care, noting 
any clinically significant abnormalities within the following body systems: general 
appearance; skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; back; 
musculoskeletal; extremities; genitourinary; neurological; and lymph nodes.  
Abnormal results must be recorded on source documents as well as the physical 
examination pages of the CRF; only if the abnormal finding is deemed to be clinically 
significant should this be recorded on the AE pages of the CRF. 
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
Record details of any congenital anomalies on the AE page of the CRF, and report 
as an SAE as described in Section 10.2.3.

Record any medication as described in Section 6.5.6.

Obtain details of any Ig (including monoclonal antibodies [eg, Synagis] or immune 
globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given to the 
infant participant since birth.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Review the weekly contact schedule with the parent(s)/legal guardian(s) and collect 
contact information OR remind the parent(s)/legal guardian(s) that a field worker will 
contact them weekly to remind them to report any MA-RTI (if applicable).

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria. An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of this study visit.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate. Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the
study visit.
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
Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the site source documents. Newly 
identified abnormal findings must be recorded on source documents and, if considered 
clinically significant in the judgment of the investigator/examiner, on the AE page of the 
CRF. Note: Standard-of-care examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee 
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria.  An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every 7 days 
from birth until the 6-month follow-up visit to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The weekly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.7.1 for guidance on reported cases of 
MA-RTIs in infant participants during the first 6 months after birth. 
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8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.

Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.
Note: Standard-of-care examination procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Ask the parent(s)/legal guardian(s) to contact the investigator immediately if any 
significant illness or hospitalization occurs or if the infant meets the MA-RTI visit
criteria.  An RTI study visit, along with a nasal swab collection, must be performed 
for all hospitalizations due to an RTI and severe MA-LRTIs as described in 
Section 1.2.4.1 and Section 8.11.8.
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
If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care as 
described above, noting any clinically significant abnormalities in the source documents. 
Newly identified abnormal findings must be recorded on source documents and, if 
considered clinically significant in the judgment of the investigator/examiner, on the AE 
page of the CRF. Only applicable if a clinic visit is conducted. Note: Standard-of-care 
examination procedures can be considered for use at this study visit, if they were 
performed within the window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants except for infant participants born during the first year of the study.

The investigator or an authorized designee completes the CRF for infant participants born 
during the first year of the study. Note: An additional 12-month blinded follow-up period 
for longer-term RTI surveillance and safety oversight will be included for these 
participants.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Confirm the understanding of the infant participant’s parent(s)/legal guardian(s) 
regarding site contact for the study, which is approximately every month (28 to 35 days) 
until the end-of-study visit. Ask the parent(s)/legal guardian(s) to contact the 
investigational site/field worker promptly if the infant meets the MA-RTI visit criteria.  
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The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days After Birth; 
Infant Participants Born During the First Year of the Study Only)

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 
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Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 742 Days After 
Birth; Infant Participants Born During the First Year of the Study)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if 
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care, noting 
any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF. 
Only applicable if a clinic visit is conducted. Note: Standard-of-care examination 
procedures can be considered for use at this study visit, if they were performed within the 
window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents. 

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants born during the first year of the study.
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8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 Months After 
Delivery)

This is an active surveillance period spanning from birth through 6 months after delivery 
(Visit 3). Note: Reporting MA-RTI events should commence 72 hours after the infant’s 
delivery.  Respiratory distress events associated with and within 72 hours of birth should 
not be captured as MA-RTI events for the study but should be captured as AEs/SAEs 
(if applicable).

The sponsor may alter the frequency of the weekly contacts or the duration of 
surveillance for MA-RTI based on RSV surveillance data or other operational factors.
8.11.7.1. Study Visits Following a Medically Attended RTI – Hospital, Home, or Clinic 
Visit

Contact the infant participant’s parent(s)/legal guardian(s) approximately every week 
(7 to 10 days) from birth until Visit 3 (6-month follow-up visit), to remind the 
parent(s)/legal guardian(s) to contact the investigational site promptly if the infant meets 
the criteria for an MA-RTI event.  The weekly contact may be via the e-diary device or 
study-related mobile application, text, email, phone call, or face-to-face contact with the 
site staff/field worker. Please refer to Table 1 regarding clinical signs and symptoms that 
meet the study definition of an MA-RTI, and Section 1.2.4.1 for study-required 
assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by:
o
The infant caregiver during or within 10 days following the MA-RTI visit
OR
o
The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an event requiring a visit to a healthcare provider, the site staff 
and/field worker should confirm, based on information provided, whether the event meets 
the criteria for an MA-RTI. Please refer to Table 1 and Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

When an infant MA-RTI criterion is met or confirmed, the site/field worker will obtain 
records from the medically attended visit and record the healthcare information as 
detailed in Appendix 6.
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
When an infant MA-RTI criterion is met or confirmed, the infant participant will be 
seen as soon as possible and optimally within 72 hours or up to 10 days for an RTI study 
visit by the investigational site staff or qualified designee. 

The infant participant may be seen either at the time of the MA-RTI, at home or at the 
study site (if discharged), or if the infant participant has been hospitalized or is receiving 
treatment at another medical facility, the site staff/field worker can conduct the RTI study 
visit at those facilities.
o
If the RTI study visit is not performed within 72 hours of the event, it should still be 
performed, including the collection of nasal swab specimens. 
o
Targeted assessments at an RTI study visit include but are not limited to:
o
Respiratory signs: lower chest wall indrawing.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Nasal swab collection from the infant participant for testing at the central 
laboratory.
o
Body weight

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site/field worker if the infant’s 
illness worsens, or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for the event as detailed in Section 8.1.
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8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit Criteria

This is a long-term surveillance procedure for all infant participants from 6 months after 
delivery (Visit 3) until the last study visit.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) from Visit 3 (6-month follow-up visit) until the end-of-study visit, to 
remind the parent(s)/legal guardian(s) to contact the investigational site promptly if the 
infant meets the criteria for an MA-RTI visit.  The monthly contact may be via the 
e-diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by: 
o
The infant caregiver during or within 10 days following the MA-RTI visit
OR
o
The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an MA-RTI, the site should obtain additional information and 
determine whether the event also meets the study definition of a severe MA-LRTI.
o
Note: Severe MA-LRTI is defined in Table 1.

The site/field worker will obtain records from the medically attended visit and record the 
healthcare information as detailed in Appendix 6.

When an infant MA-RTI criterion is confirmed and also meets the study definition of 
hospitalization due to an RTI or a severe MA-LRTI, the infant participant will be seen 
as soon as possible and optimally within 72 hours or up to 10 days for an RTI study 
visit that includes a nasal swab collection by the investigational site staff/field worker. 
The staff/field worker will obtain the nasal swab optimally within 72 hours or up to 
10 days of the event with the infant participant either at home (if discharged) or, if the 
infant participant has been hospitalized or receiving treatment at another medical facility, 
the site staff/field worker will conduct the visit at those facilities.
o
Note: Nasal swab collection from the infant participant is for testing at the central 
laboratory.
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A targeted RTI study visit will be required for all reported cases of hospitalization due to 
an RTI or severe MA-LRTI only, and this includes but is not limited to:
o
Respiratory signs: lower chest wall indrawing, failure to respond/unconsciousness.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Body weight

A targeted RTI study visit is not required for an MA-RTI event not meeting the definition 
of hospitalization due to an RTI or severe MA-LRTI.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the MA-RTI event, including emergency room or
hospitalization details with admission and discharge date (if applicable).

Record any medication as described in Section 6.5.6.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.  Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site if the infant’s illness worsens, 
or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Compile the adjudication submission package for hospitalizations due to an RTI and 
severe MA-LRTI events only as detailed in Section 8.1.
8.12. Nasal Swab Collection
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI 
visit during the RSV surveillance period from 72 hours after delivery until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of an MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1).
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The nasal swab sample is to be collected as soon as possible and optimally within 72 hours or 
up to 10 days of an MA-RTI visit in either the infant participant’s home or a medical setting 
(eg, clinic, hospital, etc) by the investigational site staff. 
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), the 
nasal swab can be collected by the infant’s caregiver or the HCP assessing the infant 
(in addition to any samples obtained in the course of routine clinical care) for processing at a 
Pfizer central laboratory, as detailed in Section 8.11.7.1 and Section 8.11.8.
In the event that these restrictions prevent taking RTI study swabs at the investigational site, 
the infant’s caregiver will be given a study nasal swab collection kit including shipping 
instructions, to be used if necessary. The infant caregiver or the HCP assessing the infant 
during an MA-RTI visit may assist the investigational sites by collecting of the study nasal 
swab samples, as required.
Note: Investigational site staff will review the procedures for nasal swab sample collection 
and shipping instructions with each infant caregiver and ensure that he/she understands the 
appropriate procedures for collecting and packaging samples for shipment to the study site.
The process for nasal swab collection and transport to the Pfizer central laboratory via study 
sites is detailed in the ISF.
8.13. Communication and Use of Technology
In a study of this duration that is event-driven, it is vital to ensure that communication 
between the study site and the maternal participant and parent(s)/legal guardian(s) is 
maintained to ensure that endpoint events are not missed.  This study will employ various 
methods, tailored to the individual participant (maternal and/or infant participant), to ensure 
that communication is maintained and study information can be transmitted securely.  Using 
appropriate technology, a communication pathway between the maternal participant and 
parent(s)/legal guardian(s) and the study site staff will be established.  The maternal 
participant and the parent(s)/legal guardian(s) may be able to utilize their own devices to 
access this technology, or use a device provided by the sponsor.  Traditional methods of 
telephone communication will also be available. The technology solution may facilitate the 
following:

Contact with the investigator.

The ability of the maternal participant/parent(s)/legal guardian(s) to report MA-RTI visits
associated with the infant participant.

An alert in the event that the maternal or infant participant is hospitalized.

Visit reminders.
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
Messages of thanks and encouragement from the study team.

A platform for recording local reactions and systemic events (e-diary).
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in an SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Estimands and Statistical Hypotheses
The null hypothesis to be tested concerns VE for the primary endpoints. The RSV vaccine 
will be compared to placebo, testing the hypotheses H0: VE ≤20% vs Ha: VE 20%. For all 
secondary efficacy endpoints, the RSV vaccine will be compared to placebo, testing the 
hypotheses H0: VE ≤0% vs Ha: VE >0%. Hypothesis testing of the secondary endpoints is 
conditional upon rejection of the null hypothesis for at least 1 of the primary endpoints.
9.1.1. Estimands – Infant Participants
9.1.1.1. Efficacy
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with key protocol criteria (evaluable participants): 

VE, defined as the percentage relative risk reduction in the incidence of MA-LRTI due to 
RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of severe MA-LRTI 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of hospitalization 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of all-cause 
MA-LRTI in the RSV vaccine group, relative to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  For participants who 
discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
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9.1.1.2. Immunogenicity
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with the key protocol criteria (evaluable participants):

Functional antibody levels estimated by the GMT for RSV A and RSV B serum
neutralizing titers.

Geometric mean ratio (GMR), estimated by the ratio of the GMTs for RSV A and RSV B
serum neutralizing titers of the RSV vaccine group to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as missing completely at random (MCAR) is assumed.  For participants 
who discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.3. Safety
In infant participants born to the maternal participants receiving 1 dose of investigational 
product:

The percentage of infant participants with specific birth outcomes.

The percentage of infant participants having AEs from birth through 1 month of age.

The percentage of infant participants having SAEs, NDCMCs, and new diagnosed 
congenital anomalies from birth through the last study visit.
Missing AE dates and missing AE intensity will be handled according to Pfizer safety rules.
9.1.2. Estimands – Maternal Participants
9.1.2.1. Immunogenicity
In maternal participants receiving 1 dose of investigational product and in compliance with 
the key protocol criteria (evaluable participants):

The immune response, estimated by the GMT for RSV A and RSV B serum neutralizing 
titers.

The immune response, estimated by the GMFR from baseline in RSV A and RSV B 
serum neutralizing titers.

GMR, estimated by the ratio of the GMTs for RSV A and RSV B serum neutralizing 
titers of the RSV vaccine group to the placebo group.
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
Geometric mean of the IgG levels against RSV prefusion F.

Geometric mean of the Ig levels to nonvaccine RSV antigens.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as MCAR is assumed.  For participants who discontinue from the study 
or have major protocol violations, all postdiscontinuation or postviolation observations will 
be censored.
9.1.2.2. Safety
In maternal participants receiving 1 dose of investigational product:

The percentage of maternal participants reporting AEs through 1 month after vaccination.

The percentage of maternal participants reporting obstetric complications and SAEs 
through the end of the study.

The percentage of maternal participants reporting local reactions within 7 days of 
vaccination.

The percentage of maternal participants reporting systemic events within 7 days of 
vaccination.
Missing e-diary data will not be imputed; missing AE dates and missing AE intensity will be 
handled according to Pfizer safety rules.
9.2. Sample Size Determination
This is an event-driven study. Sample size is determined as the number of participants to be 
randomized that is expected to accrue the required number of primary endpoint cases in the 
evaluable population. In this study there are 2 primary endpoints, and success on either 
primary endpoint is sufficient (see Section 9.1); power for the study overall is therefore at 
least as high as the power for either primary endpoint individually. In order for the study to 
have at least 90% power to reject the null hypothesis for MA-LRTI due to RSV when true 
VE is 60%, a total of 124 cases of MA-LRTI due to RSV within 90 days of birth are required 
in the evaluable population. This also accounts for potential use of an alpha of 1.25% 
1-sided within the multiplicity adjustment. There is no explicit case target for the endpoint of 
severe MA-LRTI due to RSV; depending on the assumed true VE, power for that individual 
hypothesis may be lower, but the power for the primary endpoint family will be at least 90%. 
Hypotheses about VE may be restated as hypotheses about the proportion of cases in the 
RSV vaccine group, conditional upon a fixed total number of cases. If this proportion is p, 
the null hypothesis H0: VE ≤20% is equivalent to H0: p ≥0.444; the assumption of VE = 60% 
corresponds to p = 0.286. Power was evaluated by the exact binomial test, and the case 
target established as that number k for which power is guaranteed to be at least 90%, for all 
k* ≥k. The calculation accounted for the study design (1:1 randomization of participants to 
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RSV vaccine : placebo), a single planned interim analysis of efficacy (see Section 9.5), and 
an overall type 1 error of 2.5% 1-sided across the 2 primary endpoints. 
This global study is planned to be conducted in the United States and other high-income 
countries as well as LMICs. Incidence rates of the primary endpoints are expected to vary in 
different regions. Based on a recently completed Phase 3 trial of an RSV vaccine, the 
assumed incidence rate for MA-LRTI due to RSV through 90 days in low-incidence 
countries, such as the United States, is approximately 1.75%; and in other regions,
approximately 3.90%. With these assumptions, and also allowing for 60% VE and 10% of 
enrolled participants being nonevaluable, enrollment of approximately 6900 participants is 
planned for the study as a whole. The exact number of participants required to accrue the 
case target may be higher or lower than this, depending on incidence rates, observed VE, and 
the proportion of participants evaluable.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined for infant and maternal 
participants:
Population
Description
Enrolled 
All maternal participants who sign the ICD.
Randomly assigned to 
investigational product
All maternal participants who are assigned a randomization 
number in the IRT system.
Evaluable efficacy –
infant (per-protocol)
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized at least 14 days prior to delivery, did not 
receive palivizumab or another monoclonal antibody targeting 
RSV, have no major protocol violations, and did not have 
transfusions of more than 20 ml/kg of any blood products at 
<180 days. 
Modified intent-to-treat 
(mITT) efficacy – infant
All infant participants who are born to vaccinated maternal 
participants.
Evaluable 
immunogenicity – infant
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized, have blood drawn for assay testing 
within the specified time frame, have valid and determinate 
assay results for the proposed analysis, and have no major 
protocol violations. 
Evaluable 
immunogenicity –
maternal
All maternal participants who are eligible, receive the 
investigational product to which they were randomized, have 
blood drawn for assay testing within the specified time frame, 
have valid and determinate assay results for the proposed 
analysis, and have no major protocol violations. 
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Population
Description
mITT immunogenicity –
infant
All infant participants who are born to vaccinated maternal 
participants and have at least 1 valid and determinate assay 
result for the proposed analysis.
mITT immunogenicity –
maternal
All randomized maternal participants who receive 
investigational product and have at least 1 valid and determinate 
assay result for the proposed analysis. 
Safety – infant
All infant participants who are born to vaccinated maternal 
participants.
Safety – maternal
All randomized maternal participants who receive 
investigational product.
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock for the first planned analysis 
and will describe the participant populations to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data.  This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The analysis of efficacy will use a conditional exact test based on the 
binomial distribution of the number of disease cases in the RSV vaccine 
group, given the total number of cases in both groups. The incidence of 
MA-LRTI due to RSV and severe MA-LRTI due to RSV in infant 
participants will be evaluated in both groups up to 90 days, 120 days, 
150 days, and 180 days after birth.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population. 

The 2 primary endpoints of MA-LRTI due to RSV and severe 
MA-LRTI due to RSV will be tested in parallel using a multiplicity 
adjustment procedure. Success of the trial requires rejection of the null 
hypothesis (ie, a CI lower bound >20%) for either one of the 2 primary 
endpoints.

The primary endpoint of severe MA-LRTI due to RSV may be demoted 
to a secondary endpoint, if there are insufficient cases for an adequately 
powered analysis. During the trial, blinded accrual of cases will be 
monitored and prior to any unblinding, a decision rule for this change 
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Endpoint
Statistical Analysis Methods
will be established based on the total number of cases of severe 
MA-LRTI due to RSV.

Testing of the 2 primary endpoints across the time intervals will follow a 
fixed sequence with a gatekeeping strategy. First, the hypothesis 
pertaining to the incidence of the 2 primary endpoints within 90 days 
after birth will be tested, at the full multiplicity-adjusted alpha level, 
using a multiplicity adjustment for the 2 endpoints. If that null 
hypothesis cannot be rejected, testing ends. Otherwise, testing proceeds 
to the incidence within 120 days after birth. Only primary endpoint(s)
that are successful at all earlier time intervals will be considered at 
subsequent intervals. Testing will proceed to the endpoints evaluated at 
150 days and 180 days, conditional on rejection of the null hypotheses 
for all earlier time intervals. Refer to the SAP for full details of the 
testing sequence and multiplicity correction strategy.

There may be a single interim analysis of the MA-LRTI-due-to-RSV
endpoint when there is an adequate number of cases (at least half the 
target number within 90 days). Based on the fraction of cases included 
in the interim analysis, an alpha level will be derived based on a
Lan-DeMets implementation of the O’Brien-Fleming alpha spending 
function. For example, if there is a single interim analysis at exactly 
50% of the cases, the appropriate 1-sided significance levels are 0.0014 
at the interim analysis and 0.0245 at the final analysis. Implementation 
of these 1-sided significance levels ensures the overall type 1 error for 
the primary endpoint will be no more than 0.025. See Section 9.5 for 
more details.

At the interim analysis there will also be an assessment for futility, based 
on conditional power for the MA-LRTI-due-to-RSV endpoint. If the 
probability of success at the end of the trial is low, given the interim 
analysis results and the initially assumed VE is applied to the remaining 
data, consideration will be given to stopping the study for futility.

CIs for VE will be calculated using the appropriate multiplicity-adjusted 
alpha level α. If the lower 100(1 - α)% confidence limit for VE exceeds 
20%, the null hypothesis for that endpoint will be rejected.

At the end of the trial, the RSV vaccine may be deemed efficacious if 
there are 43 or fewer cases of MA-LRTI due to RSV in the RSV vaccine 
group out of the 124 total primary endpoint cases.  This corresponds to 
estimated VE = 47% with 95.1% CI = (22%, 64%). For severe MA-
LRTI, assuming a total of 50 cases occur, the vaccine may be deemed 
efficacious if there are 14 or fewer cases in the RSV vaccine group.  
This corresponds to estimated VE = 61% with 95.1% CI = (26%, 81%).
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Endpoint
Statistical Analysis Methods
For both of these examples, it is assumed a 1-sided alpha of 0.0245 
applies to the endpoint in question. A smaller multiplicity-adjusted alpha 
may apply, leading to a higher VE required for success. 

Kaplan-Meier curves showing accrual of primary endpoint cases over 
180 days will be presented.
Secondary

The analysis of secondary efficacy endpoints will use the exact 
conditional binomial method, as for the primary endpoint. Secondary 
endpoints will be examined at the final analysis only. VE will be 
estimated along with 2-sided 95% CI. 

Inference for the secondary endpoints will be conditional upon 
demonstrating success for one of the primary efficacy endpoints. The 
secondary endpoints of hospitalizations due to RSV, all-cause MA-LRTI, 
and MA-LRTI beyond 180 days will be tested in parallel so as to 
preserve the overall type 1 error across primary and secondary endpoint 
families at no more than 2.5% 1-sided. Multiplicity correction strategies 
will be defined in the SAP. VE will be evaluated sequentially at 90 days, 
120 days, 150 days, 180 days, and 360 days for hospitalization due to 
RSV and all-cause MA-LRTI and at 210 days, 240 days, 270 days, and 
360 days for MA-LRTI due to RSV. Testing will only proceed to later 
time points conditional on success of all previous time points. 

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.
Exploratory

The incidence in infant participants of MA-RTIs due to RSV with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized.

The incidence in infant participants of MA-RTIs due to any cause with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized. All MA-RTIs and severe MA-LRTIs will be summarized 
separately.

The incidence in infant participants of MA-LRTIs due to RSV occurring 
361 to 730 days after birth will be summarized. 

The incidence in infant participants of severe MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized. 
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Endpoint
Statistical Analysis Methods

The incidence in infant participants of hospitalization due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The primary endpoint through 180 days after birth will be summarized 
separately as cases associated with RSV subgroup A or RSV subgroup B 
infection.

The primary endpoint through 180 days after birth will be summarized 
by interval from vaccination to delivery and by GA at the time of 
vaccination.

The incidence of MA-RTI, MA-LRTI, and severe MA-LRTI due to RSV 
occurring 0 to 730 days after birth in premature infants (<37 weeks GA) 
will be summarized.

The incidence of MA-RTI due to any cause in maternal participants from 
vaccination through 180 days after delivery will be summarized. 
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

A 3-tier approach will be used to summarize AEs. For both Tier 1 and 
Tier 2 events, the 95% CIs for the difference in the percentage of 
participants reporting the events between the RSV vaccine group and the 
placebo group will be calculated using the test statistic proposed by 
Miettinen and Nurminen; in addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in the percentage of 
participants reporting the events, based on the same test statistic and under 
the assumption that the test statistic is asymptotically normally distributed.  
A Medical Dictionary for Regulatory Activities (MedDRA) preferred term 
is defined as a Tier 2 event if there are 1% or more participants in at least 
1 vaccine group reporting the event.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
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dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Secondary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Exploratory 
Subgroup analyses of safety will be performed based on age at vaccination 
(18 years, ≥18 years). These and other exploratory analyses will be 
described in the SAP, finalized before first database lock.
9.4.3. Other Analyses 
9.4.3.1. Immunogenicity Analyses
Immunogenicity endpoints are exploratory in the study.  The analyses of immunogenicity 
endpoints will be based on the evaluable populations.  An additional analysis will be 
performed based on the mITT populations if there is enough difference between the mITT 
populations and the evaluable populations.  Immunogenicity data for maternal participants 
and infant participants will be summarized separately, with the exception of maternal-to-
infant placental transfer analysis.  Participants will be summarized according to the vaccine 
group to which they (for maternal participants) or their mothers (for infant participants) were 
randomized.
The secondary and exploratory immunogenicity endpoints will be described by the following 
summaries and the 95% CIs:

GMT of the RSV A and RSV B serum neutralizing titers at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMT of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMFR for RSV A and RSV B serum neutralizing titers from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).
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
GMFR of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMR of the RSV vaccine group to the placebo group for the RSV A and 
RSV B serum neutralizing titers at each available time point after vaccination (maternal 
participants and infant participants, separately).

GMR of the RSV vaccine group to the placebo group for the combined RSV A/B serum
neutralizing titers at each available time point after vaccination (maternal participants and 
infant participants, separately).

Geometric mean of the IgG levels against RSV prefusion F and Ig levels to nonvaccine 
RSV antigens at each available time point by vaccine group (maternal participants and 
infant participants, separately).

Geometric mean of IgG subclass levels (minimally IgG1) against RSV prefusion F at 
each available time point by vaccine group (maternal participants only).
Empirical reverse cumulative distribution curves (RCDCs) for combinations of time points 
and vaccine groups will be presented for RSV A and RSV B serum neutralizing titers.
A sensitivity analysis will be performed to exclude immunogenicity data from mothers and 
their infants following onset of RSV infection between vaccination and delivery (based on 
evidence from the nonvaccine antigen assay). 
Subgroup analyses of the secondary and exploratory immunogenicity endpoints will be 
performed, including an analysis based on GA at the time of vaccination, age at vaccination 
(18 years, ≥18 years), time from vaccination to delivery, and by country subcategories. All 
subgroup analyses will be defined in the SAP.
In addition, the maternal-to-infant placental transfer ratio (infant/mother) of RSV A and 
RSV B serum neutralizing titers and associated 95% CI will be summarized.
9.4.3.2. Healthcare Utilization Analyses
Healthcare utilization endpoints are exploratory in the study; these analyses will be described 
in the SAP and finalized before first database lock. For these analyses, details of healthcare 
resource utilization for all infants will be assessed at each MA-RTI visit from 72 hours after 
the infant’s delivery through the last study visit (730 days after birth). Univariate summaries
of healthcare resource utilization variables will be compared between the RSVpreF and 
placebo groups. The summarized variables may include the following: number and type 
(eg, respiratory, reactive airway disease [RAD]/asthma/wheezing) of medical visits 
(eg, outpatient, urgent care, emergency room, hospitalization, ICU), length of hospital stay, 
requirement for mechanical ventilation (yes/no, total number of episodes, total number of 
hours/days on treatment), requirement for IV fluids, requirement for respiratory diagnostic 
procedures (eg, chest radiograph, supplemental oxygen, pulse oximetry), requirement for 
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prescriptions (eg, total number of prescriptions, selected respiratory medications 
[eg, bronchodilators, corticosteroid therapy, racemic epinephrine]), and antibiotic use 
(eg, total number of prescriptions, number of use days).
9.5. Interim Analyses
An interim analysis may be performed to assess efficacy and safety after at least 50% of the 
planned number of cases of MA-LRTI due to RSV have occurred. Because of the relatively 
low number of cases of severe MA-LRTI due to RSV expected, the interim analysis will not 
consider that endpoint. Interim analysis results may be used for internal business decisions 
regarding future study planning, stopping for futility, or stopping for early success.
The order of cases included in the interim analysis will be determined by the adjudication 
committee as those first confirmed as meeting the protocol-defined criteria. When the target 
number of cases for the interim analysis is reached, it is possible that additional potential 
cases will be under adjudication. These additional cases will be included in the interim 
analysis only if confirmed as cases by the EAC on the same day that the last per-protocol 
case is confirmed.
The analysis of efficacy will utilize an O’Brien-Fleming alpha spending rule based on the 
fraction of cases of MA-LRTI due to RSV available. For example, to control the overall 
type 1 error for the primary endpoint at 2.5% 1-sided, an interim analysis at 50% of the target 
number of cases would use a 1-sided significance level of 0.14%. The final analysis at the 
target number of cases would use a 1-sided significance level of 2.45%. The alpha levels 
used at interim and final analyses will depend on the exact fraction of cases available at the 
interim analysis.
Testing of the primary endpoints at the interim analysis will follow the sequence of 
interval-specific tests as described in Section 9.4.1.  However, consideration will be given to 
stopping the study for efficacy only if all time intervals through 180 days indicate statistically 
significant efficacy. Secondary endpoints will not be tested at the interim analysis.
Futility will also be assessed using conditional power. Full details will be defined in the 
SAP. For example, if there are 62 cases available for the interim analysis, Table 7 indicates 
case splits for which stopping the study will be considered. The actual number of cases 
available may be slightly higher or lower than 62, and the decision rules amended 
accordingly.
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Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals at an 
Interim Analysis
Total Cases
RSV Vaccine 
Group Cases
Placebo Group 
Cases
VE (CI)a
Notes
62
29
33
12% (-49%, 49%)
Conditional power 
<20%,b possible 
futility declaration
62
15
47
68% (24%, 88%)
Maximum number 
of RSV cases 
permitted to declare 
VE >20%
Abbreviation: VE = vaccine efficacy.
a.
99.7% confidence level for efficacy declaration; 95% confidence level for futility.
b.
Other conditional power levels may be considered as a trigger for a futility decision.
Before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan, and method of maintaining the study blind as per Pfizer’s standard 
operating procedures (SOPs) will be documented and approved in the DMC charter.  In 
addition, the analysis details must be documented and approved in an interim analysis SAP 
or final SAP.
9.5.1. Data Monitoring Committee
This study will use an E-DMC.  Refer to the E-DMC charter for further details.
The E-DMC will review safety data at defined intervals as specified in the charter.  The 
E-DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.
The E-DMC may review unblinded data during closed meeting sessions; however, the 
sponsor will remain blinded and will not be permitted access to the randomization 
assignments until the database is locked and unblinded.
After each meeting, the E-DMC will make recommendations that may include continuing the 
study with or without modification or pausing or stopping vaccination for safety or other 
reasons.
The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints, to regulatory authorities, as appropriate.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the maternal 
participant and her parent(s)/legal guardian (if a minor) and answer all questions regarding 
the study.
Maternal participants must be informed that their participation is voluntary.  Maternal 
participants and their parent(s)/legal guardian (if a minor) will be required to sign a statement 
of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant and her parent(s)/legal guardian (if a 
minor) is fully informed about the nature and objectives of the study, the sharing of data 
related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data. 
The participant and her parent(s)/legal guardian (if a minor) must be informed that his/her 
personal study-related data will be used by the sponsor in accordance with local data 
protection law.  The level of disclosure must also be explained to the participant.
The participant and her parent(s)/legal guardian (if a minor) must be informed that his/her
medical records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities.
The investigator further must ensure that each study participant or his or her parent(s)/legal 
guardian(s) is fully informed about his or her right to access and correct his or her personal 
data and to withdraw consent for the processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
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Participants and parent(s)/legal guardian(s) must be reconsented to the most current version 
of the ICD(s) during their participation in the study.
A copy of the ICD(s) must be provided to the maternal participant or the parent(s)/legal 
guardian(s).
A study-specific assent form will be provided to maternal participants denoted to be “minor 
participants” as required by local regulations.  It is to be understood as the “minor” maternal 
participants will participate in a trial after having received age-appropriate information and is 
sometimes also referred to as “knowing agreement.”  If the study includes minor participants 
who reach the age of majority during the study, as recognized under local law, they must 
reconsent as adults to remain in the study.  If the enrollment of emancipated minors is 
permitted by the study age criteria, the IRB/EC, and local law, they must provide 
documentation of legal status to give consent without the permission of a parent or legal 
guardian.
Before any study-specific activity is performed, the investigator, or a person designated by 
the investigator, will obtain written informed consent from each maternal participant and her 
parent(s)/legal guardian (if a minor).  This will include written informed consent for the 
mother and the fetus during the pregnancy, and the infant’s continuation in the study after 
delivery.  Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements.
Participants and their parent(s)/legal guardian (if a minor) who are rescreened may be 
required to sign a new ICD as per IRB, local regulations, etc.
If during the study, the investigator determines that the maternal participant is for any reason 
no longer capable of providing informed consent, the infant’s continued participation in the 
study requires consent to be obtained from the parent(s)/legal guardian as determined by 
local regulations, legal requirements, and the IRB/EC. 
Note: For the infant participant, the term parent(s)/legal guardian denotes the “legally 
authorized representative.”
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
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To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the
requirements of local laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
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www.pfizer.com
Pfizer posts public disclosure synopses (clinical study report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the US Basic 
Results document is posted to www.clinicaltrials.gov.
Documents Within Marketing Authorization Packages/Submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
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The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan/contracts.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
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10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the site Source Data Agreement 
Plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study 
(or study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
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intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
For maternal immunization clinical studies conducted in pregnant women, data on the EDP
including any SAEs/nonserious AEs as well as pregnancy outcomes are collected and 
analyzed in the clinical database. All SAEs are reported to Pfizer Safety using the Vaccine 
SAE Reporting Form. In case of a new pregnancy in a maternal participant before the end of 
the study, any exposure to the investigational product is reportable to Pfizer Safety within 
24 hours of investigator awareness using the Vaccine SAE Reporting Form/EDP 
supplemental form.
The term “participant” in this section refers to (1) the maternal participant and her fetus; and 
after delivery (2) the maternal participant and (3) the infant participant.
10.2.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (eg, cesarean section, endoscopy, appendectomy): the 
condition that leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs)
An NDCMC is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
10.2.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
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c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting.  Complications that occur during hospitalization are AEs.  If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious.  When in 
doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a Pfizer 
product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited 
cases by pharmacovigilance personnel.  Such cases are also considered for reporting as 
product defects, if appropriate.
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10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording safety events on the CRF and 
for reporting safety events on the Vaccine SAE Reporting Form to Pfizer Safety.  These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and 
(3) occupational exposure. 
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE 
Reporting Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study via 
occupational exposure
Occupational exposure is 
not recorded.
Occupational exposure 
(regardless of whether 
associated with an AE)
Note:  Include all AEs/SAEs 
associated with occupational 
exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
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Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING
to describe the maximum intensity of the AE. For purposes of 
consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent
intervention indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.
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
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused the 
event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible.  This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any anonymized 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.2.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
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10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
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
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with International 
Organization for Standardization (ISO) 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.4.1. Definition of AE and ADE
AE and ADE Definition 

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational medical device.  
This definition includes events related to the investigational medical device or 
comparator for study participants, users, and other persons.  This definition also 
includes events considered related to procedures for study participants only.

An ADE is defined as an AE related to the use of an investigational medical device.  
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
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10.4.2. Definition of Serious Adverse Event, Serious Adverse Device Effect, and 
Unanticipated Serious Adverse Device Effect
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is an AE that:
a. Led to death.
b. Led to serious deterioration in the health of the participant, that either resulted 
in:

A life-threatening illness or injury.  The term “life-threatening” in the definition of 
serious refers to an event in which the participant was at risk of death at the time of 
the event. It does not refer to an event that hypothetically might have caused death, 
if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
SADE Definition

A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE.
Unanticipated Serious Adverse Device Effect (USADE) Definition

A USADE is a serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis management 
file.
10.4.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance.  Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
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10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator 
to review all documentation (eg, hospital progress notes, laboratory reports, and 
diagnostic reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information in 
the participant’s medical records, in accordance with the investigator’s normal clinical 
practice and on the appropriate form of the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of following the reporting process described in the IP 
manual.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
“severe” should not be confused with an SAE. “Severe” is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as “severe.”

An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as “severe.”
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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency and has 
provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE/SAE/Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE/SAE/ device deficiency 
as fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
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10.4.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred 
method to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.4.6. Reporting of SADEs
SADE Reporting to Pfizer Safety 
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.
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10.5. Appendix 5: Background Factors
1. Information on the following will be collected at Visit 1, Visit 4 (12-Month), and 
Visit 6 (24-Month) for all infant participants:

Educational level of parent(s) or legal guardian(s).

Exposure to smoke (including tobacco smoke).

Number of persons in the household ≥18 years of age.

Number of children <18 years of age in the household and if they attend school/ 
daycare.
o
Number of children in the household under 5 years of age (under 60 months).
o
Number of children in the household ≥5 years of age (≥60 months).
2. Information on the following will be collected at each postbirth visit:

Childcare/daycare (for infant participants).

Breastfeeding information (including whether or not breastfeeding is exclusive).
3. Information on the following will be collected at each RTI study visit:

Number of missed days of work for parent(s) or legal guardian(s) due to the infant 
participant’s illness.
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10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria Checklist 
for MA-RTI Visit – Infant Participants
When an infant MA-RTI medical visit criterion is met or confirmed, the site will obtain 
records from the medical visit and capture the healthcare information as detailed below in the 
eCRF. This information is based on respiratory-related assessments including examination 
findings, clinical findings, and any pathogen-related assessments/findings. 
Medical Visit - Visit Details and Assessment Requirements
Note: This should not be linked to a study visit but may overlap with the RTI study visit. 
The following fields and clinical assessment details should be obtained from relevant 
records for the medically attended event prior to each RTI study visit to support the 
assessment of the RTI event.

Reason for visit including date/time, eg,
o
Nasal discharge for 24 hours or more.
o
Difficulty breathing, labored breathing, or rapid breathing for any duration.
o
Cough.
o
Inability to feed for any duration due to respiratory symptoms.
o
Apnea.
o
Any other respiratory symptom of concern.

Location of medical visit (inpatient clinic, outpatient clinic, emergency department, 
urgent care, hospitalization, home visit, other). Note: study visits should NOT be 
recorded here.
o
If hospital visit, was this triggered by an RTI (include details pertaining to duration
as well as admission and discharge information and records)?

Clinical findings pertaining to respiratory symptoms and/or RTI, as detailed below but 
not limited to:
o
Presence or absence of pertinent examination findings, eg, apnea (documented as per 
chart), wheezing, fever, cough, nasal congestion, intercostal retractions, lower chest 
wall indrawing, grunting, crackles, decreased breath sounds, other abnormal breath 
sounds, dry mucous membranes, skin tenting, sunken fontanelle, difficulty feeding, 
failure to respond/unconsciousness, etc. 
o
Respiratory rate from highest/worst value of visit.
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o
Oxygen saturation (SpO2) from lowest/worst value of visit.
o
Oxygen supplementation (assisted ventilation, including type of respiratory assistance 
[respirator, “state-of-the-art” occlusive nasal prongs, face tent, etc]).

Days of supplementary oxygen.

Use of nasal cannula.

Use of high-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive).
o
Heart rate from worst value of visit when performed consistently.
o
Body weight from the date of the MA-RTI event.
o
Temperature from worst value of visit when performed consistently.
o
Additional clinical or respiratory related assessments including chest x-ray.

Local test results for RSV as part of routine clinical care:
o
Testing platform used (clinical list of all platforms and validated by research).
o
Result (list: positive, negative, indeterminate, other).

Results for any local non-RSV respiratory pathogen testing conducted as part of routine 
clinical care:
o
Result (list: detected, not detected, indeterminate)

Record the provider diagnosis, including any causative pathogen (if applicable), eg, RSV 
bronchiolitis, asthma, influenza, etc.

Obtain details of all prescribed medications including IV fluid usage.

Obtain details of all AEs/SAEs in line with study requirements. Note: MA-RTIs are not 
AEs/SAEs, unless related to the investigational product or resulting in death.
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10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
10.7.1. Informed Consent for the Maternal Participants <20 Years Old
Informed consent for maternal participants <20 years old and their infant participants will be 
obtained based on current Japanese civil code article 753 until 01 April 2022.

Married maternal participants 16 to <20 years of age are deemed to have reached 
“majority” and each maternal participant will sign the ICD for her and her infant’s study 
participation.

The maternal participants 16 years of age and unmarried maternal participants 16 to <20 
years of age are deemed “minors.”

When the maternal participant is a minor under local law, the investigator, or a person 
designated by the investigator, will obtain written informed consent from the maternal 
participant’s legally acceptable representative, parent(s), or legal guardian as well as 
the maternal participant’s assent (affirmative agreement) for her and her child’s study 
participation before any study-specific activity is performed. The investigator will 
retain the original of each signed consent and assent document.

The assent form for a minor must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements, including applicable privacy 
laws.

The assent form for a minor used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB before use, and available for 
inspection.

The investigator must ensure that the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian is fully informed about the nature and 
objectives of the study and possible risks associated with participation.

The source documents must record that the maternal participant was a minor at 
the time of signing the ICD, how the investigator determined that the person 
signing the consent was the maternal participant’s legally acceptable 
representative, the consent signer’s relationship to the maternal participant 
(eg, parent), and that the maternal participant’s assent was obtained.

When the minor maternal participants reach the age of majority during the study, as 
recognized under local law, they must reconsent as adults to remain in the study.
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
Beginning on 01 April 2022, when the amended civil law in which individuals 18 years 
of age and older are deemed to have reached majority and marriage age for women is 
implemented:

The investigator, or a person designated by the investigator, will obtain written informed 
consent from the maternal participant 18 to <20 years of age and married maternal 
participants 16 to <18 years of age.  

For all maternal participants <16 years of age and unmarried maternal participants 16 to 
<18 years of age, the investigator, or a person designated by the investigator, will obtain 
written informed consent from the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian as well as the maternal participant’s assent.
10.7.2. Temperature Measurement and Definition of Fever

Axillary temperature will be measured at Visit 1 and as required at an unscheduled visit, 
and will be measured by the maternal participants for 7 days following vaccination.

For the maternal participants enrolled in Japan, an axillary temperature of ≥37.5°C
(99.5°F) meets the definition of a current febrile illness in the criteria for temporarily 
delaying vaccine administration described in Section 5.2.3.

For the purpose of recording the temperature in the e-diary, fever is defined as an axillary
temperature of ≥38.0°C (100.4°F) for maternal participants enrolled in Japan.
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants
As Study C3671008 is a first-in-Japanese study and in accordance with a recommendation 
from the Pharmaceuticals and Medical Devices Agency (PMDA), the study will utilize a 
sentinel cohort for the maternal participants enrolled in Japan with progression to study 
enrollment at all study sites after a safety review (data from each maternal participant 
through 14 days after vaccination).  In addition to the study procedures and requirements 
specified in the protocol for Study C3671008, the following procedures will be required for 
the maternal participants enrolled in the sentinel cohort in Japan.
10.7.3.1. Enrollment of Maternal Participants in the Sentinel Cohort
In the sentinel cohort, approximately 8 maternal participants will be enrolled.  No more than 
4 maternal participants per day can be randomized.  Vaccination of the remaining maternal 
participants in the sentinel cohort will commence no sooner than 48 hours after the fourth 
participant received her vaccination.  
10.7.3.2. Conclusion of the Sentinel Cohort
After enrollment in the sentinel cohort is completed, the Pfizer internal review committee 
(IRC) will review at least 14 days of postvaccination safety data from all maternal 
participants enrolled in the sentinel cohort, including all local reactions, systemic events, and 
AEs.  An acceptable review will trigger an expansion of study enrollment to all study sites in 
Japan. Refer to the IRC charter for further details.
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10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or Telephone; 14 to 16 Days 
After Vaccination)
All maternal and infant participants enrolled in this study will follow the protocol for 
Study C3671008.  In addition, the maternal participants enrolled in the sentinel cohort in 
Japan will have a Day 15 follow-up visit conducted either at the study site or via telephone.  
This visit should be conducted 14 to 16 days after vaccination. 

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given since the last visit.

Review the participant’s e-diary data.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6.

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit.
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10.7.3.4. Schedule of Activities for Maternal Participants Enrolled in the Sentinel Cohort in Japan
The following table provides an overview of the protocol visits and procedures for the maternal participants enrolled in the sentinel 
cohort in Japan.  Refer to Section 1.2.3.1 for the Schedule of Activities for the Maternal Participants: RTI Surveillance for Medically 
Attended Respiratory Tract Illness Visits (Vaccination Until the End-of-Study Visit).
Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to 
Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current/former alcohol, tobacco, marijuana, or 
any illicit drug usage
X
Record vital signs
X
Targeted physical and obstetric examination performed 
on the same day or within 7 days before the vaccination 
visit
X
Record details of any antenatal and/or postnatal steroid 
treatment, monoclonal antibodies, blood products, or 
Rho(D) immune globulin
X
X
X
X
X
Record details of the maternal participant’s GBS status 
and if any medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
X
Review eligibility criteria
X
X
X
X
Review temporary delay criteria
X
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Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to 
Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Prevaccination blood draw for serologic assessment
(~15 mL) on the same day or within 7 days before the 
vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and 
measuring devicef
X
Obtain and record baseline assessment of prespecified 
systemic events on the day of and prior to vaccination
in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 30 minutes) and 
assessment of immediate AEs
X
Delivery blood draw for serologic assessment 
(~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X
X
Record AEs, as appropriateh
X----------------------------------------------------X
Record SAEs, as appropriateh
X
X
X
X
X
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Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to 
Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of the schedule of 
activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; ICD = informed 
consent document; MA-RTI = medically attended respiratory tract illness.
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal partic
eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) a baseline 
assessment of prespecified systemic events on the day of and prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination 
(where Day 1 is the day of vaccination).  Remind maternal participants that the study staff/field worker may contact them to obtain additional information 
on events entered into the e-diary.  Ask maternal participants to contact the investigator or site staff immediately if they are prompted by the e-diary from 
Day 1 to Day 7 following vaccination, to determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal 
participant may be referred to the appropriate healthcare facility at the discretion of the study staff/field worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 28 days after vaccination.  From the signing of 
the ICD until the maternal participant completes the study, all SAEs will be collected.  Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
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10.7.4. Exclusion Criterion 12 Clarification
For exclusion criterion 12, “Current alcohol abuse or illicit drug use. Note: Marijuana use is 
not considered an exclusion criterion for the study when elicited in participant screening, 
though it may be considered illicit in some locales.” In Section 5.2.1, any current use of an 
illicit drug including marijuana will not be permitted for maternal participants enrolling from 
study sites in Japan.
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and Unanticipated SAE
Caused by Medical Device
Definition of SAE caused by medical device:
An SAE caused by medical device is defined as an AE caused by a medical device which led 
to an outcome characteristic to SAEs, or a device-related incident whose recurrence might 
lead to death or serious deterioration in health.
NOTE: See the Medical Device Adverse Events, Adverse Device Effects, Serious Adverse 
Events, and Device Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting section (Appendix 4). Deficiencies fulfilling the definition of an 
AE/SAE will also follow the processes outlined in Section 8.3.3 and Appendix 2 of the 
protocol.
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix – Applicable 
to the Philippines, Gambia, and South Africa Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Participants who have not had ultrasound assessments to determine eligibility during 
routine care should be consented, and have an ultrasound within 90 days prior to 
vaccination in order to comply with inclusion criteria #1 in Section 5.1.1.
Safety endpoints:
The time period and frequency for collecting AE and SAE information by the investigator 
and site staff should follow Appendix 2, with the exception of the additional screening 
window for sites conducting ultrasounds procedures from -90 to -28 days. At these sites, the 
safety reporting periods should be as follows:

AEs occurring up to 48 hours after ultrasound assessment that the investigator 
deems are related to the study procedure must be reported in the CRF.

The active collection period for SAEs begins once informed consent has been 
provided until the maternal participant completes the study.

The active collection period for nonserious AEs begins 28 days prior to 
vaccination and continues through a minimum of 28 calendar days after
vaccination as described in Section 8.3.1 and Section 10.2.
MA-RTI endpoints:
Maternal MA-RTIs are collected from the time of vaccination to the end of the study period 
as described in Section 8.1.2.
Note: For maternal participants who are screen failures, the active collection period ends 
when screen failure status is determined. 
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10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to South 
Korea and Taiwan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Section 5.1.1: Inclusion criterion 1 states that healthy women ≤49 years of age who are 
between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an 
uncomplicated, singleton pregnancy, who are at no known increased risk for complications 
are eligible for the study.
Please find below country-specific minimum age requirements for study entry into the 
protocol:

In South Korea, the minimum age requirement of maternal participants who can be 
enrolled into the study is ≥19 years of age.

In Taiwan, the minimum age requirement of maternal participants who can be 
enrolled into the study is ≥20 years of age.
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10.10. Appendix 10: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ADE
adverse device effect
AESI
adverse event of special interest
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
Apgar
appearance, pulse, grimace, activity, and respiration
AST
aspartate aminotransferase
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
Clinical Laboratory Improvement Amendments
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EAC
endpoint adjudication committee
EACC
endpoint adjudication committee charter
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine 
GA
gestational age
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Abbreviation
Term
GBS
group B streptococcal
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBIG
hepatitis B immune globulin
HBV
hepatitis B virus
HCP
healthcare provider
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IAP
intrapartum antibiotic prophylaxis
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
Ig
immunoglobulin
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ISF
investigator site file
ISO
International Organization for Standardization
IUI
intrauterine insemination
IV
intravenous
IWR
interactive Web-based response
LFT
liver function test
LMIC
lower- and middle-income country
LMP
last menstrual period
LRTI
lower respiratory tract illness
MA-LRTI
medically attended lower respiratory tract illness
MA-RTI
medically attended respiratory tract illness
MCAR
missing completely at random
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NAAT
nucleic acid amplification technology
NDCMC
newly diagnosed chronic medical condition
PCD
primary completion date
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Abbreviation
Term
PCR
polymerase chain reaction
PFS
prefilled syringe
PMDA
Pharmaceuticals and Medical Devices Agency
PT
prothrombin time
RAD
reactive airway disease
RCDC
reverse cumulative distribution curve
RSV
respiratory syncytial virus
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RTI
respiratory tract illness
RT-PCR
reverse transcription–polymerase chain reaction
SAE
serious adverse event
SADE
serious adverse device effect
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2 
SMS
short message service
SoA
schedule of activities
SOP
standard operating procedure 
SpO2
oxygen saturation
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Tdap
tetanus, diphtheria, and acellular pertussis vaccine
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VE
vaccine efficacy
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11. REFERENCES
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Graham BS. Biological challenges and technological opportunities for respiratory 
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Regen AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization 
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Final Protocol Amendment 3, 26 August 2020
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLINDED,
PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND 
SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F 
SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING 
PREGNANCY
Investigational Product Number:
PF-06928316 
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine 
United States (US) Investigational New 
Drug (IND) Number:
017931
European Clinical Trials Database 
(EudraCT) Number:
2019-002943-85
Protocol Number:
C3671008
Phase:
3
Short Title: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants 
Born to Women Vaccinated During Pregnancy.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original protocol
05 December
2019
Not applicable (N/A)
Protocol 
Amendment 1
24 March 2020
PROTOCOL SUMMARY: Clarification text was 
added in various sections of the main body of the 
protocol to match the revisions made to the protocol 
summary.
Throughout: The protocol now contains final 
wording regarding the double-blinded, placebo-
controlled study design and the final dose and 
formulation of the respiratory syncytial virus 
stabilized prefusion F subunit vaccine (RSVpreF). 
This is as a result of the analysis of the safety, 
tolerability, and immunogenicity data from the 
C3671003 maternal Phase 2b trial.
Section 1.2.1 Study Design – Maternal Participants: 
The final dose and formulation of RSVpreF were 
inserted, including the lyophile match for the 
placebo.
Section 1.2.2 Study Design – Infant Participants: 
The text box pertaining to the vaccine group arms 
was deleted. The maternal-infant dyads will be 
randomly assigned in this study. Rationale: Infant 
participants will not be administered the 
investigational product. Therefore, the current 
placement is potentially confusing to readers.
Section 1.2.3 Schedule of Activities for Maternal 
Participants, Section 5.2.3, and Section 8.10.1: 
Clarification text was added as follows:
o
The immunogenicity blood collection and 
physical examination window requirements 
before vaccination were aligned to provide 
greater logistical convenience for the 
investigational sites with respect to enrolling 
participants into the study.
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Document
Version Date
Summary of Changes and Rationale
o
The wording for the study objectives pertaining 
to the request for intrapartum antibiotic 
prophylaxis (IAP) details for maternal 
participants with a group B streptococcal (GBS) 
status was revised to be consistent with the 
study procedural objectives, which are to collect 
GBS status and to ascertain whether any 
medication was given for IAP. This resulted in 
the deletion of the text in Section 6.5.3, as this 
information is captured in Section 8.10.3.
o
A reference to the immunogenicity blood draws 
for maternal participants was added to clarify 
the adverse event (AE) reporting requirements 
for events that might occur as a result of study-
related procedures.
Section 1.2.3.1 Schedule of Activities for Maternal 
Participants – Respiratory Tract Illness (RTI) 
Surveillance for Medically Attended Respiratory 
Tract Illness (MA-RTI) Visits: 
o
Details to be collected during an MA-RTI were 
revised.
o
Clarification was added regarding the safety 
reporting requirements for MA-RTI events that 
might occur during the study. 
Section 1.2.4 Schedule of Activities for Infant 
Participants: 
o
Visit flexibility was increased to prioritize 
participant safety and adherence to local 
guidance in the event of a coronavirus disease 
2019 (COVID-19) outbreak or other outbreaks. 
o
The physical examination and vital sign 
assessment windows for the study were aligned 
to provide greater logistical convenience for the 
investigational sites with respect to compliance 
to study protocol requirements.  
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Document
Version Date
Summary of Changes and Rationale
o
The protocol safety reporting criteria and period 
for adverse events (AEs), serious adverse events 
(SAEs), and newly diagnosed chronic medical 
conditions (NDCMCs) were streamlined.
Section 1.2.4.1 Schedule of Activities for Infant 
Participants: RTI Study Visits During the Study: 
The table was revised, including splitting the 
schedules of activities for unscheduled RTI visits 
for all infant participants into RTI surveillance from 
birth to 6 months and RTI surveillance from 6 
months to the end of the study. The procedures were 
streamlined for these RTI study visits to improve 
clarity and consistency.
Table 1: Clarification has been added as to when a 
study visit is triggered for reported MA-RTI 
endpoint events on the study. Day 1 is the day of the 
MA-RTI visit as detailed in Section 8.11.7.
In addition, clarification has been added as to what 
constitutes the site source for confirmed study 
endpoint criteria, in order to provide the sites 
guidance on what documentation will eventually be 
submitted to the endpoint adjudication committee 
(EAC) for evaluation.
Section 3.1: The exploratory endpoints were revised 
to correspond with the planned statistical analyses 
of RTI events in the pediatric population. This does 
not represent a change to the study design but 
instead better reflects the total statistical analysis 
plan. 
Section 3.1, Section 3.2, and throughout: To 
improve clarity and ensure consistency, the use of 
“RSV-neutralizing antibody titers” has been 
changed to RSV serum neutralizing titers.” This is 
the sponsor’s preference based on what the 
neutralizing activity assay is based upon, and in this 
case, it is whole serum and not just the purified 
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antibodies during these immunogenicity 
assessments.
Section 3.3, Section 8.1.1.2, Section 8.1.3, and 
Section 10.2: For further clarification, the protocol’s 
safety and endpoint reporting requirements were 
amended to ensure consistency with Pfizer’s 
updated safety reporting requirements for endpoint-
defined studies.
Section 4.3: The text “availability of these data are 
expected in 2020” was removed as this statement 
does not accurately reflect the current decision-
making process for the dose and formulation 
selection activities for this study. 
Section 5.2.1: Clarification text was added to the 
exclusion criterion for body mass index (BMI) and 
congenital anomalies based on study requirements.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: The 
tetanus, diphtheria, and acellular pertussis vaccine 
(Tdap) administration requirements text was 
modified to describe the timing of vaccinations 
based on data from the C3671004 study, once 
available. This change will better reflect clinical 
practice and will facilitate recruitment of suitable 
maternal participants for the study.
Section 6.1.1, Section 6.1.3, Section 8.4, and 
Section 8.10.1: Clarification text was added to 
address investigational product reconstitution 
volume and administration requirements. This 
change is to ensure consistency with the 
investigational product administration 
documentation for the study.  
Section 7.2: Clarification text was added to address 
the notification process for biological sample 
management in the event of study participant 
withdrawal from the study.
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Version Date
Summary of Changes and Rationale
Section 7.3 and Appendix 1 Informed Consent 
Process: Clarification text was added to address 
study retention and data collection requirements for 
the study. In addition, further clarification has been 
added to emphasize the informed consent process 
during circumstances where the maternal participant 
is no longer able to provide consent but the infant 
participant’s continued participation in the study 
could be retained by the parent(s)/legal guardian as 
per local regulatory, local laws, and local 
governance approval.
Section 8.1.1.1: Clarification text was added to 
provide guidance regarding the midturbinate swab 
processing requirements and the definition of 
acceptable certified/accredited laboratory bodies for 
this process in the study.
Section 8.2.1.1 and Section 8.10.1: The reporting 
requirements for Grade 4 local reactions in the study 
were clarified; the assessment and reporting are 
carried out by the investigators (or appropriately 
qualified designees).
Section 8.3.1.1, Section 8.3.1.2, Section 8.3.5.1, 
Section 8.3.5.2, Section 8.10, and Section 8.11: The 
reporting requirements were clarified for this 
vulnerable patient population with regard to AEs 
and SAEs likely to occur in the study in women 
with gestational age (GA) eligibility criterion 
between 24 0/7 and 36 0/7 weeks.
Section 8.3.6: Text was added to address and 
standardize reporting procedures for adverse events 
of special interest (AESIs) for this patient 
population.
Section 8.3.7 and Appendix 4: Several Pfizer text 
revisions were incorporated regarding device 
deficiencies and the safety reporting requirements 
for this study.
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Section 8.10: The immunogenicity blood collection 
and physical examination window requirements 
before vaccination were aligned to provide greater 
logistical convenience for the investigational sites 
with respect to enrolling participants into the study.  
Section 8.10.1: The prepregnancy BMI text 
revisions in Section 5.2.1 were aligned with the 
study assessment requirements for maternal 
participants at screening.
Section 8.10.2, Section 8.10.3, Section 8.10.4, and 
Section 8.10.6: Clarification text was added to the 
MA-RTI reporting requirements for maternal 
participants in the study to provide guidance and 
ensure the investigational sites provide accurate 
information pertaining to these self-reported events.
Section 8.11.1 to Section 8.11.6: Clarification text 
was added (where applicable) to address the 
following study assessments:
o
“Birth weight must be the first birth weight and 
cannot be based on the standard-of-care 
examination” was removed as this statement is 
confusing to the investigational sites. Birth 
weight assessments have now been realigned 
with standard-of-care assessments at the study 
visit to aid compliance with study assessments 
and requirements.
o
Clarification text was added regarding the 
reporting of standard-of-care measurements for 
vital sign assessments. 
o
In addition, the physical examination and vital 
sign assessment windows for the study were 
aligned to provide greater logistical convenience 
for the investigational sites to comply with study 
protocol requirements.  
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o
For further clarification, the RTI study visit 
assessment requirements were amended to 
emphasize the difference between the MA-RTI 
visit criteria and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements. 
Section 8.11.7.1: For further clarification, the RTI 
study visit assessment requirements have been 
amended to emphasize the following:
o
The RTI study visit window, including nasal 
swab collection from the MA-RTI notification 
for the infant participant.
o
Duplicate text was removed pertaining to the 
MA-RTI definition and the signs and symptoms 
of interest pertinent to an RTI study visit. 
o
Guidance regarding the difference between the 
MA-RTI visit and the subsequent study visit 
after the event has been reported. This is to 
improve clarity and consistency with the RTI 
study visit requirements.
Section 8.11.8: Clarification text was added to 
address the RTI study visit window, including nasal 
swab collection from the MA-RTI notification for 
the infant participant.
o
For further clarification, the RTI study visit 
assessment requirements have been amended to 
emphasize the difference between the MA-RTI 
visit and the subsequent study visit after the 
event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements and provide guidance to the 
investigational sites.
Section 9.1.2.1, Section 9.1.2.2, Section 9.4.1, 
Section 9.2, and Section 9.5: Text was added to 
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clarify the statistical analysis procedures in line with 
the current revisions.
Appendix 2: Clarification text was added to support 
the safety and pregnancy outcome reporting 
requirements for participants who may experience 
exposure during pregnancy while in the study.
Appendix 5: Further clarification was added to the 
background factors of interest during the infant’s 
participation in the study. 
Appendix 6: Clarification text was added to the 
examination and treatment criteria checklist for 
reported MA-RTI visits.  This is to ensure there is 
some consistency to the source records provided for 
these events in relation to the protocol requirements.
Throughout: Several changes were made to 
incorporate the replacement of the Clinical Trial 
Serious Adverse Event Report Form (CT SAE 
Report Form) to Vaccine SAE Reporting Form, as 
part of the new vaccine SAE reporting requirements 
for Pfizer. 
Throughout: Minor editorial revisions were 
incorporated as appropriate. 
Protocol 
Amendment 2
26 June 2020
Section 5.1.1: Administrative update was
incorporated to address the recently added 
Appendices 7 and 8.
Appendix 7: A country-specific appendix was added 
for Japan to address consent/assent issues for 
minors, temperature measurement, definition of 
fever, and enrollment of maternal participants in the 
sentinel cohort for safety monitoring.
Appendix 8: A country-specific appendix was added 
for the Gambia and South Africa to address an 
extension to the screening period for maternal 
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participants with regard to GA requirements and 
consent process.
Protocol 
Amendment 3
26 August 2020
PROTOCOL SUMMARY: Added clarification text 
to the exploratory endpoint section for the infant 
participants; changes were made in the protocol 
summary to match the revisions made in the main 
body of the protocol.
Section 1.2.2: Study Design – Infant Participants: 
Added text to address RSV seasonality and the 
required RTI surveillance periods during the study. 
Rationale: The previous placement was potentially 
confusing to readers. The revisions provide clarity 
to the investigational sites with regard to the RTI 
surveillance follow-up activities.
Section 1.2.3 and Section 1.2.3.1: Added 
clarification text (where applicable) to address the 
following: 
o
Added “Home or Telephone” to the type of visit 
options allowed for the 6-month-postdelivery 
visit.
o
Added clarification text to the alcohol history 
reporting requirements and included “obstetric” 
in the screening assessment requirements for the 
study.
o
Added “study staff,” as study personnel are 
allowed to collect and report baseline and 
reactogenicity assessments reported during the 
evaluation period.
o
Added clarification text regarding the reporting 
requirements for AEs, SAEs, and MA-RTIs for 
maternal participants.
Section 1.2.4 - Schedule of Activities for Infant 
Participants: 
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o
Added “Home” to the type of visit options 
allowed for the 1-month and 6-month follow-up 
visits and added further clarification to the visit 
status during potential COVID-19 pandemic
situations or other natural disasters. Rationale: 
Infant participant visit options were aligned with 
the maternal participant requirements to allow 
for visit flexibility.
o
For further clarification, the physical 
examination and vital sign assessment
expectations at birth and at the 1-month visit 
were aligned to provide greater logistical 
convenience for the investigational sites to 
comply with study protocol requirements.
Sections 1.2.4, 1.2.4.1, 8.1.1, and 8.11 to 8.12:
Added clarification text (where applicable).
o
To address alternate nasal swab collection 
procedures, if needed, during potential 
COVID-19 pandemic situations or other natural 
disasters.
o
Clarification text was added with regards to the
start of the reporting period for MA-RTI events 
upon the infant’s delivery.  This is to improve 
clarity and consistency with the capturing and 
reporting requirements for MA-RTI events and 
provide guidance to the investigational sites.
Sections 1.2.4.1, 8.11.7.1, 8.11.8, and Appendix 6: 
o
Added temperature and body weight 
measurements for infant participants during 
study RTI visits.
o
For vital sign measurements, especially oxygen 
saturation measurements (where applicable), 
clarification text was added to state that it is 
recommended that the participant not be 
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receiving supplemental oxygen at the time of 
measurement.
These updates are to ensure consistency with the 
study RTI assessment visits after a confirmed 
MA-RTI event.
Section 3.1: Added clarification text as follows:
o
Table 1.
Primary and Secondary Endpoint 
Events and Definitions in Infant Participants: 
For further clarification, added descriptive text 
to the table header to address endpoint events 
listed within the table. In addition, made 
corrections to the overlapping respiratory rate 
measurements provided for some study endpoint 
events. These changes were made to improve 
clarity and consistency with the endpoint 
reporting and evaluation process for the study.
o
For the infant participant exploratory objectives,
added the planned statistical analysis period of
“after 6 months of age” to “all-cause MA-RTIs 
and hospitalizations due to RSV” in the 
pediatric population based on regulatory 
authority feedback from South Korea.
o
Incorporated revisions to align endpoints with 
study duration, specifically MA-LRTIs due to 
RSV A and RSV B, and MA-RTIs associated 
with non-RSV respiratory pathogens.
o
Added clarification text to address the analysis 
plans for the healthcare utilization endpoints.
Section 4.1: For further clarification, added text to 
address the desire to enroll across gestational age.
Section 4.3: Added a brief summary of the safety 
and immunogenicity results from the C3671003 trial 
to support the decision-making process for this 
study.
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Section 5.1.1: Inserted administrative 
update/clarification text with regards to:
o
Participant eligibility guidance documentation 
available within the investigator site file.
o
The informed consent process for maternal 
participants.
Section 5.2.1: Based on study requirements:

Added clarification text to exclusion criterion 7, 
which addresses the investigator’s judgment 
when assessing participant eligibility (maternal 
participant or her fetus) and regional endemic 
conditions during routine maternal care, as per 
local standards of care and obstetric 
recommendations.

Added clarification text to address illicit drug 
use pertaining to marijuana.
Section 5.2.2: Deleted the infant participants
exclusionary criterion pertaining to the “receipt of 
investigational or approved monoclonal antibodies 
against RSV.”  This was to provide additional 
clarification to the investigational sites with regards 
to the infant’s eligibility criteria.
Sections 5.2.3, 6.5.1, and 6.5.2: Modified the Tdap
administration requirements text to describe the 
timing of vaccinations based on recent data from the 
C3671004 study (A Phase 2b, Placebo-Controlled, 
Randomized, Observer-Blind Study to Evaluate the 
Safety, Tolerability, and Immunogenicity of a 
Respiratory Syncytial Virus (RSV) Vaccine When 
Administered Concomitantly With Tetanus, 
Diphtheria, and Acellular Pertussis Vaccine (Tdap) 
in Healthy Nonpregnant Women 18 Through 49 
Years of Age; ClinicalTrials.gov identifier: 
NCT04071158).
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Section 6.1.4: Added text to clarify what constitutes 
a medical device with regards to the investigational 
product in this study.
Section 6.5.2: Added text to clarify the tetanus and 
diphtheria vaccine administration requirements 
during the study.
Section 6.5.4: For further clarification, added text to 
address prohibited vaccinations and treatments for 
infant participants.  This is to provide guidance to 
the investigational sites.
Section 6.5.5: Added text to clarify the permitted 
treatments, vaccines, and procedures acceptable to 
infant participants enrolled in the study.
Sections 8.2.1 to 8.2.1.2 and Section 8.10.1: For 
further clarification, amended the e-diary 
completion requirements to emphasize the different 
reporting and/recording options for reactogenicity 
events should illiterate maternal participants be 
enrolled in the study. This is to improve clarity and 
consistency with the reactogenicity reporting 
requirements at the investigational sites.
Table 6 and Section 8.2.1.3: Based on regulatory 
feedback, provided a description of the intensity 
scale for the reactogenicity event “fever.”
Sections 8.3.1 to 8.3.1.2, Sections 8.3.5.2 to 8.3.8.1, 
and Section 10.2.3: Added clarification text (where 
applicable) to address the following safety-related 
updates and provide guidance to the investigational 
sites:
o
Several Pfizer text revisions were incorporated 
regarding the safety reporting requirements for 
this study.
o
Text was added to clarify the SAE reporting 
timelines for the study and provide guidance 
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regarding the evaluation of and assessment 
procedures for congenital anomalies.
Section 8.10.1: For further clarification, aligned the 
study assessment window requirements before 
vaccination to provide guidance and greater 
logistical convenience for the investigational sites 
with respect to enrolling participants into the study.
Section 8.10.3: Added clarification text with regards 
to the reporting requirements for maternal 
participants diagnosed as GBS positive and 
pregnancy outcome information. This is to improve 
clarity and consistency with the reporting 
requirements at investigational sites.
Section 8.11.1: Added clarification text on how the 
infant participant’s identifier will be assigned for 
this study.
Sections 8.11.1 to 8.11.6: Added clarification 
regarding the reporting of standard-of-care 
measurements for vital sign assessments, 
measurements, and physical examination 
procedures (where applicable) to provide greater 
logistical convenience for the investigational sites to 
comply with study protocol requirements.
Section 9.2 and Section 9.4.1: Modified text to more 
generally describe Type 1 error control procedures 
and refer to the statistical analysis plan (SAP) for 
details.
Section 9.4.3.2: Added clarification regarding the 
planned analyses for the healthcare utilization 
endpoints.
Section 10.2.5: Deleted the “SAE Reporting to 
Pfizer Safety via an Electronic Data Collection 
Tool” section. For consistency, only the Vaccine 
SAE Reporting Form process will be used.
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Appendix 6: Added clarification text to the 
microbiological data collection requirements for the 
study based on any pathogen-related 
assessments/findings performed as part of the 
participants routine clinical care. This is to ensure 
there is some consistency to the source records 
provided for these events in relation to the protocol 
requirements and to address regulatory guidance in 
light of the COVID-19 outbreak or other outbreaks.
Appendix 7: Added clarification text to the 
following:
o
Incorporated minor editorial revisions into the 
Schedule of Activities for Maternal Participants 
Enrolled in the Sentinel Cohort in Japan.
o
Added clarification text to exclusion criterion 12 
regarding the definition of illicit drug use based 
on country-specific requirements.
o
Incorporated clarification text regarding the 
definition of an SAE caused by a medical 
device.
Appendix 9: Added a country-specific appendix for 
South Korea and Taiwan to address the minimum 
age requirements for maternal participants in each 
country.
Throughout: Incorporated minor editorial revisions 
as appropriate.
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................24
1. PROTOCOL SUMMARY...................................................................................................25
1.1. Synopsis ..................................................................................................................25
1.2. Schematic for Study Participants ............................................................................32
1.2.1. Study Design – Maternal Participants ........................................................32
1.2.2. Study Design – Infant Participants .............................................................33
1.2.3. Schedule of Activities for Maternal Participants........................................34
1.2.3.1. Schedule of Activities for Maternal Participants: RTI 
Surveillance for Medically Attended Respiratory Tract Illness 
Visits (Vaccination Until the End-of-Study Visit) ............................37
1.2.4. Schedule of Activities for Infant Participants.............................................38
1.2.4.1. Schedule of Activities for Infant Participants: Respiratory 
Tract Illness Study Visits During the Study......................................40
2. INTRODUCTION ...............................................................................................................43
2.1. Study Rationale .......................................................................................................43
2.2. Background .............................................................................................................44
2.3. Benefit/Risk Assessment.........................................................................................45
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................46
3.1. Infant Participants ...................................................................................................46
3.2. Maternal Participants...............................................................................................50
3.3. Protocol-Defined Efficacy Endpoints .....................................................................51
4. STUDY DESIGN.................................................................................................................52
4.1. Overall Design.........................................................................................................52
4.1.1. Approximate Duration of Participation for Each Participant .....................53
4.1.2. Approximate Number of Participants.........................................................53
4.2. Scientific Rationale for Study Design.....................................................................53
4.3. Justification for Dose ..............................................................................................54
4.4. End of Study Definition ..........................................................................................55
5. STUDY POPULATION......................................................................................................55
5.1. Inclusion Criteria.....................................................................................................56
5.1.1. Inclusion Criteria – Maternal Participants..................................................56
5.1.2. Inclusion Criteria – Infant Participants.......................................................58
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5.2. Exclusion Criteria....................................................................................................58
5.2.1. Exclusion Criteria – Maternal Participants.................................................58
5.2.2. Exclusion Criteria – Infant Participants......................................................60
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants ................60
5.3. Lifestyle Considerations..........................................................................................61
5.4. Screen Failures ........................................................................................................61
6. STUDY INTERVENTION..................................................................................................61
6.1. Study Intervention(s) Administered........................................................................61
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........61
6.1.2. Placebo........................................................................................................62
6.1.3. Administration............................................................................................62
6.1.4. Medical Devices .........................................................................................62
6.2. Preparation/Handling/Storage/Accountability ........................................................63
6.2.1. Preparation and Dispensing........................................................................64
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................64
6.3.1. Blinding of Study Site Personnel................................................................64
6.3.2. Blinding of the Sponsor..............................................................................64
6.3.3. Allocation to Investigational Product .........................................................64
6.3.4. Breaking the Blind......................................................................................65
6.4. Study Intervention Compliance...............................................................................65
6.5. Concomitant Therapy..............................................................................................65
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................65
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................66
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................66
6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................67
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................67
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications –
Infant Participants............................................................................................67
6.6. Dose Modification...................................................................................................67
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6.7. Intervention After the End of the Study..................................................................67
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................68
7.1. Discontinuation of Study Intervention ....................................................................68
7.2. Participant Discontinuation/Withdrawal From the Study.......................................68
7.3. Withdrawal of Consent............................................................................................68
7.4. Lost to Follow-up....................................................................................................69
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................69
8.1. Efficacy Assessments..............................................................................................70
8.1.1. Efficacy Assessments – Infant Participants................................................70
8.1.1.1. Midturbinate Nasal Swab Collection and Testing 
Requirements for Endpoint Confirmation – Infant Participants........71
8.1.1.2. Events for Adjudication and Submission Guidance –
Infant Participants..............................................................................71
8.1.2. Exploratory Efficacy Assessments – Maternal Participants.......................72
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal 
and Infant Participants .....................................................................................73
8.1.4. Immunogenicity Assessments ....................................................................73
8.1.4.1. Total Volume of Blood Collected – Maternal Participants.......73
8.1.4.2. Total Volume of Blood Collected – Infant Participants............73
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant 
Participants ........................................................................................74
8.1.4.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development – Maternal and Infant 
Participants ........................................................................................74
8.1.4.5. Respiratory Pathogens – Infant Participants .............................74
8.1.4.6. Biological Samples – Maternal and Infant Participants............75
8.2. Safety Assessments .................................................................................................75
8.2.1. Participant Electronic Diary – Maternal Participants .................................75
8.2.1.1. Local Reactions – Maternal Participants...................................76
8.2.1.2. Systemic Events – Maternal Participants..................................78
8.2.1.3. Temperature – Maternal Participants ........................................79
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant 
Participants.......................................................................................................80
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8.3. Adverse Events and Serious Adverse Events..........................................................80
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......81
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................82
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................83
8.3.2. Method of Detecting AEs and SAEs ..........................................................84
8.3.3. Follow-up of AEs and SAEs.......................................................................84
8.3.4. Regulatory Reporting Requirements for SAEs...........................................84
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Investigational Product ..........................................................................85
8.3.5.1. Exposure During Breastfeeding ................................................85
8.3.5.2. Occupational Exposure .............................................................85
8.3.6. Cardiovascular and Death Events...............................................................86
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................86
8.3.8. Adverse Events of Special Interest.............................................................86
8.3.8.1. Lack of Efficacy........................................................................87
8.3.9. Medical Device Deficiencies......................................................................87
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........87
8.3.9.2. Follow-up of Medical Device Deficiencies...............................87
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................88
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................88
8.3.10. Medication Errors.....................................................................................88
8.4. Treatment of Overdose............................................................................................89
8.5. Pharmacokinetics ....................................................................................................90
8.6. Pharmacodynamics..................................................................................................90
8.7. Genetics...................................................................................................................90
8.7.1. Specified Genetics ......................................................................................90
8.8. Biomarkers ..............................................................................................................90
8.9. Health Economics ...................................................................................................90
8.10. Procedures – Maternal Participants.......................................................................90
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8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to 
Vaccination to Day 1 – Visit 1) .......................................................................90
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After 
Vaccination).....................................................................................................94
8.10.3. Delivery (Maternity Unit).........................................................................95
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 
210 Days After Delivery).................................................................................96
8.10.5. Unscheduled Reactogenicity Visits..........................................................97
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria –
Maternal Participants .......................................................................................99
8.11. Procedures – Infant Participants..........................................................................100
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After 
Birth)..............................................................................................................100
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After 
Birth)..............................................................................................................101
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 
Days After Birth) ...........................................................................................103
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 
Days After Birth) ...........................................................................................104
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days 
After Birth; Infant Participants Born During the First Year of the Study 
Only) ..............................................................................................................105
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 
742 Days After Birth; Infant Participants Born During the First Year of 
the Study).......................................................................................................106
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 
Months After Delivery)..................................................................................107
8.11.7.1. Study Visits Following a Medically Attended RTI –
Hospital, Home, or Clinic Visit.......................................................107
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit 
Criteria ...........................................................................................................109
8.12. Nasal Swab Collection ........................................................................................110
8.13. Communication and Use of Technology.............................................................111
9. STATISTICAL CONSIDERATIONS ..............................................................................112
9.1. Estimands and Statistical Hypotheses...................................................................112
9.1.1. Estimands – Infant Participants ................................................................112
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9.1.1.1. Efficacy ...................................................................................112
9.1.1.2. Immunogenicity ......................................................................113
9.1.1.3. Safety.......................................................................................113
9.1.2. Estimands – Maternal Participants ...........................................................113
9.1.2.1. Immunogenicity ......................................................................113
9.1.2.2. Safety.......................................................................................114
9.2. Sample Size Determination...................................................................................114
9.3. Populations for Analysis .......................................................................................115
9.4. Statistical Analyses ...............................................................................................116
9.4.1. Efficacy Analyses .....................................................................................116
9.4.2. Safety Analyses ........................................................................................119
9.4.3. Other Analyses..........................................................................................120
9.4.3.1. Immunogenicity Analyses.......................................................120
9.4.3.2. Healthcare Utilization Analyses..............................................121
9.5. Interim Analyses ...................................................................................................122
9.5.1. Data Monitoring Committee.....................................................................123
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................124
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............124
10.1.1. Regulatory and Ethical Considerations ..................................................124
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................124
10.1.2. Financial Disclosure ...............................................................................125
10.1.3. Informed Consent Process ......................................................................125
10.1.4. Data Protection .......................................................................................126
10.1.5. Dissemination of Clinical Study Data ....................................................127
10.1.6. Data Quality Assurance ..........................................................................128
10.1.7. Source Documents..................................................................................129
10.1.8. Study and Site Closure............................................................................129
10.1.9. Publication Policy...................................................................................130
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................131
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................132
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10.2.1. Definition of AE .....................................................................................132
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs).................133
10.2.3. Definition of SAE...................................................................................133
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs.....................135
10.2.5. Reporting of SAEs..................................................................................138
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......139
10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting............................................141
10.4.1. Definition of AE and ADE .....................................................................141
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device 
Effect, and Unanticipated Serious Adverse Device Effect............................142
10.4.3. Definition of Device Deficiency.............................................................142
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................143
10.4.5. Reporting of SAEs..................................................................................145
10.4.6. Reporting of SADEs...............................................................................145
10.5. Appendix 5: Background Factors........................................................................146
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria 
Checklist for MA-RTI Visit – Infant Participants...................................................147
10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only...............149
10.7.1. Informed Consent for the Maternal Participants 18 to <20 Years 
Old..................................................................................................................149
10.7.2. Temperature Measurement and Definition of Fever ..............................150
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants.........150
10.7.3.1. Enrollment of Maternal Participants in the Sentinel 
Cohort..............................................................................................150
10.7.3.2. Conclusion of the Sentinel Cohort ........................................150
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or 
Telephone; 14 to 16 Days After Vaccination).................................150
10.7.3.4. Schedule of Activities for Maternal Participants Enrolled 
in the Sentinel Cohort in Japan........................................................152
10.7.4. Exclusion Criterion 12 Clarification.......................................................155
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and 
Unanticipated SAE Caused by Medical Device ............................................155
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix –
Applicable to the Gambia and South Africa Only...................................................156
10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to 
South Korea and Taiwan Only ................................................................................157
10.10. Appendix 10: Abbreviations .............................................................................158
11. REFERENCES ................................................................................................................161
LIST OF TABLES
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants ...............................................................................................46
Table 2.
Endpoint Events and Definitions in Maternal Participants.......................50
Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained....................................................................................................74
Table 4.
Grading Scale for Local Reactions...........................................................77
Table 5.
Grading Scale for Systemic Events ..........................................................79
Table 6.
Ranges for Fever.......................................................................................80
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals 
at an Interim Analysis.............................................................................122
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Indication
Pfizer’s respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSVpreF) 
is a prophylactic vaccine that is being investigated for the prevention of medically attended
RSV-associated lower respiratory tract illness (LRTI) in infants by active immunization of 
pregnant women.
Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given the global burden of disease, maternal immunization offers an attractive 
strategy for infant disease prevention.  Both preclinical studies in animals and interim data 
from a Phase 1/2 study in healthy nonpregnant adults have demonstrated acceptable 
tolerability and safety of RSVpreF.  A robust immune response has also been observed in 
participants from the aforementioned trial. RSVpreF is currently under assessment in healthy 
pregnant women 18 through 49 years of age (Study C3671003: A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blinded Trial to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT04032093).
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
lower respiratory tract illness (MA-LRTI) in infants.
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Objectives, Estimands, and Endpoints 
Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC): 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants 
born to maternal 
participants receiving 
1 dose of investigational 
product, the percentage 
of participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

Adverse events (AEs) from birth to 
1 month of age.

Serious adverse events (SAEs) and 
newly diagnosed chronic medical 
conditions (NDCMCs):
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants 
enrolled during the first year of 
the study).
Secondary Efficacy Objectives
– Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of medically attended 
respiratory tract illness 
(MA-RTI) due to RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs 
from vaccination up to 730 days after 
birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 6 months 
of age.
MA-LRTIs due to RSV occurring 181 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth. 
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV in infants after 6 months 
of age.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA--LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI
in the study population. 
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth. 
To assess the impact of 
RSVpreF on RSV illness based 
on socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
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To assess the effect of RSVpreF 
on healthcare utilization. 
Univariate summaries of healthcare 
utilization variables, which may include 
the following: number and type of 
medical visits, length of hospital stay, 
requirement for mechanical ventilation, 
requirement for respiratory diagnostic 
procedures, requirement for intravenous 
(IV) fluids, requirement for prescriptions, 
and antibiotic use.
Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimand
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery 
study visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum
neutralizing titers and prefusion F 
immunoglobulin G (IgG) titers 
measured:

before vaccination.

at delivery.
Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
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This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis section [Section 9.2]).  There is no specific case target for 
the additional primary endpoint of severe MA-LRTI. The total enrollment number of 
maternal participants may vary depending on the incidence rate of the primary endpoint in 
the infant participants, the true underlying VE, and a potential early stop for efficacy or 
futility. In the event that efficacy in the infant population is demonstrated at the interim 
analysis, enrollment of maternal participants may continue in order to obtain safety 
evaluations in an adequate number of maternal and infant participants to support vaccine 
registration with national health authorities.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It is anticipated that approximately 6900 
mother-infant pairs may be needed to accumulate 124 per-protocol cases.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF will be 120 µg 
(60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study, all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term respiratory 
tract illness (RTI) surveillance and safety oversight to address safety and the possibility of 
conferred enhanced protection (antibody persistence) during a second RSV season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee.
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Planned Duration
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on gestational age (GA) at the time of vaccination and 
when the infant is actually born.
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
Data Monitoring Committee
This study will use an external data monitoring committee (E-DMC) to monitor vaccine 
safety and efficacy and study futility.
Statistical Methods
The primary hypothesis to be tested is that VE with respect to MA-LRTI due to RSV or 
severe MA-LRTI due to RSV in infants within at least 90 days after birth is more than 20%, 
relative to placebo. The 2 primary endpoints will be tested in parallel using a multiplicity 
adjustment procedure. VE will be estimated using the exact conditional binomial method. 
There will also be hierarchical testing of the primary endpoints to 120 days, 150 days, and 
180 days, conditional on success of the analysis for the shorter intervals. A single interim 
analysis of the MA-LRTI-due-to-RSV endpoint with the opportunity to stop the study for 
efficacy or futility may be included. At the end of the trial, the RSV vaccine may be deemed 
efficacious if there are 43 or fewer cases of MA-LRTI due to RSV in the RSV vaccine group 
out of the 124 total primary-endpoint cases.  This corresponds to estimated VE = 47% with 
95.1% confidence interval (CI) = (22%, 64%). For severe MA-LRTI, assuming a total of 
50 cases occur, the vaccine may be deemed efficacious if there are 14 or fewer cases in the 
RSV vaccine group.  This corresponds to estimated VE = 61% with 95.1% CI = (26%, 81%).
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1.2. Schematic for Study Participants
1.2.1. Study Design – Maternal Participants
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1.2.2. Study Design – Infant Participants
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Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
1.2.3. Schedule of Activities for Maternal Participants
Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current/former alcohol, tobacco, marijuana, or any illicit drug 
usage
X
Record vital signs
X
Targeted physical and obstetric examination performed on the same 
day or within 7 days before the vaccination visit
X
Record details of any antenatal and/or postnatal steroid treatment, 
monoclonal antibodies, blood products, or Rho(D) immune globulin
X
X
X
X
Record details of the maternal participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
Review eligibility criteria
X
X
X
Review temporary delay criteria
X
Prevaccination blood draw for serologic assessment (~15 mL) on the 
same day or within 7 days before the vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and measuring devicef
X
Obtain and record baseline assessment of prespecified systemic 
events on the day of and prior to vaccination in the e-diary
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Administer investigational product
X
Postvaccination observation (at least 30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic assessment (~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X-------------------------- X
Record AEs, as appropriateh
X-------------------------- X
Record SAEs, as appropriateh
X
X
X
X
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of 
the schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; ICD = informed 
consent document; MA-RTI = medically attended respiratory tract illness.
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic, Home, or 
Telephone
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) a 
baseline assessment of prespecified systemic events on the day of and prior to vaccination and reactogenicity events from Day 1 to Day 7 following 
vaccination (where Day 1 is the day of vaccination).  Remind maternal participants that the study staff/field worker may contact them to obtain additional 
information on events entered into the e-diary.  Ask maternal participants to contact the investigator or site staff immediately if they are prompted by the 
e-diary from Day 1 to Day 7 following vaccination, to determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the 
maternal participant may be referred to the appropriate healthcare facility at the discretion of the study staff/field worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 28 days after vaccination.  From the signing of 
the ICD until the maternal participant completes the study, all SAEs will be collected. Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or 
to have resulted in death.
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1.2.3.1. Schedule of Activities for Maternal Participants: RTI Surveillance for Medically Attended Respiratory Tract Illness
Visits (Vaccination Until the End-of-Study Visit)
Visit Description
Assessments of MA-RTIa
Visit Window
As Soon as Possible After Confirmed MA-RTI 
Type of Visit
Telephone
Record details of a confirmed MA-RTI 
X
Details of an acute illness visit AND a report of 1 or more of the following 
RTI signs and symptoms: 

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
X
Obtain standard-of-care records, including local NAAT testing results (if 
applicable)b
X
Record nonstudy vaccine information
X
Record AEs and SAEs, as appropriatec
X
Complete the CRF with details 
X
Abbreviations: CRF = case report form; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness.
a.
Confirmed cases of MA-RTI will be collected from vaccination until the maternal participant completes the study. The assessment of the event would 
involve a telephone call, or a clinic visit if determined by the investigator to be warranted. 
b.
Site staff will review and collect data pertaining to the illness and any local NAAT testing results (RSV, influenza, etc), if available.
c.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  MA-RTI events will not be captured as safety 
events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to have resulted in death. Please see 
Section 8.3.1 for reporting requirements and timelines.
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1.2.4. Schedule of Activities for Infant Participants
Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the 
First Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-
up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 
Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Assign infant participant identifier
X
Demography 
X
Collect background factorsc
X
X
X
X
X
X
Collect birth outcome information including 
infant’s birth data and appearance, pulse, 
grimace, activity, and respiration (Apgar) score
X
Obtain and record infant’s length, head 
circumference, and weight
X
X
X
X
(if clinic visit)
X
(if clinic visit)
Physical examination including vital signs
(temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate) performed within 48 hours 
after birth
X
Obtain and record vital signs, including 
temperature, heart rate, SpO2 by pulse oximetry, 
and respiratory rate
X
Targeted physical examination (record in the site 
source document)
X
X
X
(if clinic visit)
X
(if clinic visit)
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole 
blood, packed cells)
X
X
X
X
X
X
Review eligibility
X
Cord blood sample (~10 mL) for serologic 
assessmentd
X
Record AEs, as appropriatee
X
Record NDCMCs and SAEs, as appropriatee
X
X
X
X
X
X
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Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the 
First Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-
up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 
Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic or 
Home
Clinic or Home
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Surveillance reminder contact
Contact with the infant 
participants’ parent(s) or 
legal guardian(s)
approximately every week 
until Visit 3
From Visit 3, contact with the infant participant’s parent(s) or legal guardian(s), 
approximately every 28 to 35 days until the end of the study
Assessment of MA-RTIsf,g
Assessment of MA-RTI 
events during the active RSV 
surveillance period as 
detailed in Section 1.2.4.1 of 
the schedule of activities
Assessment of MA-RTI events as detailed in Section 1.2.4.1 of the schedule of 
activities
Abbreviations: MA-RTI = medically attended respiratory tract illness; NDCMC = newly diagnosed chronic medical condition; RSV = respiratory syncytial 
virus; SpO2 = oxygen saturation.
a.
Applicable only for infant participants enrolled during the first year of the study.
b.
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), study visits that cannot be conducted in the clinic or at home, in 
accordance with the protocol requirements, may be conducted via telephone. 
c.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV illness. 
d.
Cord blood must be obtained on the day of birth. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical cord has 
been clamped and cut. If cord blood is unavailable, a blood sample may be collected from the infant participant preferably within the first 24 hours but up 
to 7 days after birth. The infant’s weight must be used to determine the volume of blood that can be collected.
e.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs, NDCMCs, and SAEs through 28 days after birth.  
From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected.  An NDCMC is defined as a disease or 
medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
f.
A confirmed MA-RTI is defined as an expected study event based on the assessments detailed in the schedule of assessment in Section 1.2.4.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or 
to have resulted in death.
g.
Reporting MA-RTI events should commence 72 hours after the infant’s delivery.  Respiratory distress events associated with and within 72 hours of birth 
should not be captured as MA-RTI events on the study but should be captured as AEs/SAEs (if applicable).
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1.2.4.1. Schedule of Activities for Infant Participants: Respiratory Tract Illness Study Visits During the Study 
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After 
Confirmed MA-RTI and Within 
72 Hours (Preferable) or Up to 10 
Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Surveillance reminder contact
Contact the infant participants’ parent(s) 
or legal guardian(s) approximately every 
week until Visit 3
From Visit 3, contact the infant participants’ parent(s) or legal 
guardian(s), approximately every 28 -35 days until the end of the 
study
Record confirmed MA-RTI as detailed in Appendix 6, 
as appropriate
X
X
X
Record details of the RTI, including 1 or more of the 
following RTI signs and symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid 
breathing for any duration

Cough

Inability to feed for any duration because of 
respiratory symptoms

Apnea

Any other respiratory symptom of concern 
X
X
X
Obtain standard-of-care records and complete CRFc
X
X
X
Record local NAAT testing results, if performed and 
availabled
X
X
X
Perform RTI study visit, record targeted assessment
results (temperature, heart rate, respiratory rate, SpO2 by 
pulse oximetry, chest wall indrawing) and body weight,
and collect nasal swab (for RT-PCR)e
X
X
Record concomitant medication associated with the 
treatment of the MA-RTI
X
X
X
Collect background factors associated with MA-RTIf.
X
X
X
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After 
Confirmed MA-RTI and Within 
72 Hours (Preferable) or Up to 10 
Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole blood, 
packed cells)
X
X
X
Record AEs , NDCMCs, and SAEs, as appropriateg
X
X
X
Compile MA-RTI visit source documentation upon 
request by adjudication committee (qualifying 
RSV-positive cases only)
X
X
Abbreviations: CRF = case report form; HCP = healthcare provider; ICU = intensive care unit; IV = intravenous; MA-LRTI = medically attended lower 
respiratory tract illness; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; NDCMC = newly diagnosed 
chronic medical condition; RSV = respiratory syncytial virus; RTI = respiratory tract illness; RT-PCR = reverse transcription–polymerase chain reaction; 
SpO2 = oxygen saturation.
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After 
Confirmed MA-RTI and Within 
72 Hours (Preferable) or Up to 10 
Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
a.
If the infant participant is reported to be experiencing or has had an MA-RTI from birth until Visit 3, the site should arrange a study visit as soon as 
possible and within 72 hours (preferable) or up to 10 days. Ideally, the RTI study visit will be conducted at the investigational study site; however, it is 
possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit 
where the infant participant is residing. Note: Reporting MA-RTI events should commence 72 hours after the infant’s delivery.  
b.
If the infant participant is reported to be experiencing or has had an MA-RTI associated with severe LRTI criteria or been hospitalized for an RTI from 
Visit 3 until the end of study participation, the site should arrange a visit as soon as possible and within 72 hours (preferable) or up to 10 days of site 
awareness. Ideally, assessment of these potential endpoint events (hospitalization due to RTI or severe MA-LRTI) will be conducted at the 
investigational study site; however, it is possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is 
hospitalized) or the site staff may visit where the infant participant is residing. Note: For nonsevere MA-RTIs, a telephone contact with the infant 
participants’ parent(s) or legal guardian(s) is acceptable to complete the study visit.
c.
Obtain case records, including details of hospitalization, ICU stays, use of oxygen, IV fluids usage, etc.
d.
The site staff/field worker will review and collect data related to any local NAAT testing results, if performed and available.
e.
The site staff/field worker will collect nasal swabs for confirmed MA- RTIs, including confirmed cases of hospitalizations due to an RTI and severe MA-
LRTIs. In the event that restrictions prevent taking RTI study swabs because of an outbreak, pandemic situation, or natural disaster, the study nasal swab 
can be collected for processing at Pfizer’s central laboratory by the infant caregiver, during or within 10 days following an MA-RTI visit, or by the HCP 
assessing the infant during the MA-RTI visit (in addition to any samples obtained in the course of routine clinical care) as detailed in Sections 8.11.7.1
and 8.11.8.
f.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV. This will be collected 
for all MA-RTI events reported.
g.
The investigator and site staff/field worker will ensure the active elicitation and collection of NDCMCs and SAEs through the end-of-study visit for the 
infant participant. From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected. An NDCMC is 
defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma). 
Note: A confirmed MA-RTI will not be captured as a safety event, unless the investigator or an appropriate designee deems it to be related to the 
investigational product or to have resulted in death.
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2. INTRODUCTION
Prevention of RSV disease in young infants is a significant unmet medical need globally.  
RSV is the leading cause of bronchiolitis and viral pneumonia in infants and can lead to fatal 
respiratory distress, especially in those with risk factors including premature infants with 
underlying cardiopulmonary disease, or in the absence of effective healthcare systems.1
However, most cases of RSV disease occur in healthy, full-term infants without risk factors.2
Worldwide, RSV kills approximately 118,200 children annually, with about half of those 
deaths occurring in infants under 6 months of age, and the majority of those occurring in 
resource-limited countries.3,4 In the United States, RSV is the leading cause of infant 
hospitalization, with more than 60,000 hospitalizations of children 12 months of age and 
younger annually.5,6  There is increasing evidence that the link between severe RSV disease 
in infancy and wheezing later in childhood may be causal.7,8  Like influenza, RSV infection 
follows a seasonal pattern, causing illness primarily in the cooler months of the year in 
temperate regions and during the wet season in tropical countries with seasonal rainfall.9  
Infection is essentially universal by the time children reach 2 years of age.10
Currently, there is neither specific treatment for RSV infection nor a vaccine to protect 
against RSV disease.  Treatment consists primarily of supportive care.  A prophylactic 
humanized monoclonal antibody, palivizumab (Synagis, AstraZeneca), targeting the RSV F 
glycoprotein is available for prevention of severe RSV disease in young infants at increased 
risk.11  Limitations of its use include its high cost12 and requirement of multiple monthly 
injections,13 and so it remains recommended for use only in very premature infants and 
others at increased risk of severe illness.6,14
Nevertheless, the protective effect of Synagis provides definitive proof of principle that 
serum neutralizing antibody directed against the F protein can provide clinically meaningful 
protection against RSV lower respiratory tract disease in young infants.15  Furthermore, it is 
well known that in other disease settings, antibodies transferred from mothers to their fetuses 
across the placenta can reduce infant disease early in life,16,17,18,19,20,21 suggesting that 
maternal immunization is a reasonable approach to RSV disease prevention among young 
infants.
There are 2 antigenic variants of RSV, namely, RSV subgroup A (RSV A) and RSV 
subgroup B (RSV B).  The RSV vaccine being investigated in this study is a bivalent vaccine 
composed of stable RSV prefusion F antigens representing the 2 subgroups to help ensure the 
broadest coverage against RSV illness.
RSVpreF is a prophylactic vaccine being developed to prevent medically attended
RSV-associated LRTI in infants by active immunization of pregnant women.
2.1. Study Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given a global burden of disease in the millions of cases each year, maternal 
immunization offers an attractive strategy for infant disease prevention.  Both preclinical 
studies in animals and interim data from a Phase 1/2 study in healthy nonpregnant adults 
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have demonstrated acceptable tolerability and safety of RSVpreF.  A robust immune 
response has also been observed in the population of the aforementioned trial, at 1 month 
after vaccination. The combined RSV A and B serum neutralization geometric mean titers 
(GMTs) have been shown to be 12 to 20 times higher than those with 100 μg/mL of
palivizumab, the concentration of the monoclonal antibody that is known to provide near to 
complete protection of high-risk infants from severe RSV disease.22,23 RSVpreF is currently 
under assessment in healthy pregnant women 18 through 49 years of age (Study C3671003,
A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093).
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
RSV-associated LRTI in infants.
2.2. Background 
RSV is an important cause of morbidity and mortality worldwide, with a substantial burden 
of disease borne by young infants.  Rates of severe RSV illness are highest in infants 
6 months of age, with a peak in hospitalization between 1 and 2 months of life, though the
highest case-fatality rates are observed in the neonatal period (<1 month).2 Infants born 
prematurely and those with underlying cardiac or pulmonary disease are at further increased 
risk of severe clinical disease due to RSV.  A 2017 retrospective case analysis that examined 
RSV mortality data from 23 countries demonstrates the global nature of the seriousness of 
RSV disease, with significant morbidity and mortality occurring in both lower- and 
middle-income countries (LMICs) and high-income countries.3,4
No specific treatments for RSV exist, and available prophylactic measures (ie, RSV 
monoclonal antibody) are limited to use in only those infants at highest risk; additionally, in 
LMICs, use of available RSV prophylaxis is cost-prohibitive.  While active immunization 
against RSV in infants might be an option, multiple efforts, extending over half a century, to 
develop a safe and effective RSV vaccine to protect infants from disease have yielded little 
success.  The early peak of disease presents a further obstacle to an active vaccination 
strategy for infants.  Given these challenges, maternal immunization to protect infants early 
in life offers an attractive strategy for infant disease prevention.
The present RSV vaccine efforts were initiated in early 2014 based on a new scientific 
discovery (determination of the RSV prefusion F crystal structure)24 and a changing 
regulatory and policy environment that today supports the development of vaccines for 
maternal immunization to protect very young infants.  The trimeric RSV F surface 
glycoprotein in a prefusion conformation is now known to be the primary target of 
neutralizing antibodies and is the basis for the engineered antigens in Pfizer’s vaccine 
candidate.   Applying structure-guided vaccine design, Pfizer has developed a stabilized RSV 
prefusion F vaccine candidate.  The core hypothesis underlying Pfizer’s RSV vaccine 
development effort for prevention of infant disease is that vaccine antigens based on RSV 
prefusion F, when administered to pregnant women in the second or third trimester of 
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pregnancy, will elicit sufficiently high neutralizing antibody titers that, when the antigens are 
actively transferred transplacentally to the fetus, will protect infants against RSV disease. 
The aim is for neutralizing antibody levels to be at sufficient levels such that infants will be 
protected from birth and possibly through their first RSV season.
2.3. Benefit/Risk Assessment
RSVpreF is being evaluated in ongoing clinical studies.  Pfizer’s maternal immunization 
approach circumvents the risk of vaccine-mediated disease enhancement that was observed 
in the 1960s following direct immunization of RSV-naive infants with a formalin-inactivated 
RSV vaccine (FI-RSV).25  FI-RSV elicited a predominantly nonneutralizing antibody 
response and a Th2-biased cell-mediated response, both of which are considered potential 
contributing factors to disease enhancement.26  During preclinical studies, in a standard 
cotton rat infectious RSV challenge model, FI-RSV showed pathological signs of causing 
disease enhancement, and the current Pfizer vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease enhancement has not been reported to occur in 
RSV-experienced individuals after immunization with any RSV vaccine candidate.  Because 
pregnant women are universally RSV-experienced, they are not considered at risk for a 
disease-enhancing immune response to the vaccine that could exacerbate infection in 
themselves.  Enhanced disease has not been observed in infants born to mothers who
received prior investigational RSV vaccines; therefore, enhanced disease in infants is very
unlikely.  A previous study of maternal immunization with a Wyeth (later merged with 
Pfizer) investigational RSV vaccine (PFP-2) showed an acceptable safety profile, even 
though this candidate contained a postfusion RSV F antigen that elicited a relatively weak 
RSV-neutralizing antibody response and a higher nonneutralizing RSV-binding antibody 
response in pregnant women.27  A recently completed Phase 3 maternal RSV trial (Novavax) 
with an RSV vaccine containing F not stabilized in the prefusion form, given to over 
4600 healthy pregnant volunteers, showed a similar safety profile in the RSV vaccine and 
placebo groups.28
Vaccination with the RSV prefusion F antigens elicits a higher ratio of neutralizing to 
nonneutralizing antibodies, more closely matching the profile in naturally exposed 
individuals.  The safety profile of RSVpreF observed to date is similar to that of prior RSV F 
subunit vaccines tested in RSV-experienced adults.
There are limited data on the global burden of maternal RSV infection, likely in part because 
of infrequent diagnostic testing. However, in one multisite study, RSV-associated disease in 
pregnancy was shown to result in prolonged hospitalization and an increased likelihood of 
preterm birth in women who tested RSV-positive.29 It is possible that vaccination may 
benefit the pregnant women who receive it. RTI in mothers who receive RSVpreF will be 
explored in this study.  The benefit of maternal vaccination is accrued to the infant by means 
of transplacental antibody transfer.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the investigator’s brochure (IB), which is the 
single reference safety document (SRSD) for this study.
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Infant Participants
The study objectives and endpoints for infant participants employ the event definitions in 
Table 1.
Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study 
Endpoints/Assessments
Study Definitions
Medically attended visit
Infant participant has been taken to or seen by a healthcare provider 
(eg, outpatient or inpatient visit, emergency room, urgent care, or home 
visit)
MA-RTI visit for infant 
participant
A medically attended visit AND 1 or more of the following RTI signs and 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any 
duration

Cough

Inability to feed for any duration because of respiratory symptoms

Apnea

Any other respiratory symptom of concern 
RSV-positive testa

RSV RT-PCR–positive test result by Pfizer central laboratory
OR

RSV-positive test result by certified laboratory with NAAT for RSV
MA-RTI due to RSVb

An MA-RTI visit 
AND

RSV-positive test result as described in Section 8.1.1.1
MA-LRTI due to any cause

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age], 
≥50 bpm for ≥2 months to <12 months of age, or ≥40 bpm for 
≥12 months to 24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
MA-LRTI due to RSVb

Infant with an MA-RTI visit 
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age] or 
≥50 bpm for ≥2 to <12 months of age, or ≥40 bpm for ≥12 months to 
24 months of age) OR

SpO2 <95% OR

Chest wall indrawing 
AND 

RSV-positive test result as described in Section 8.1.1.1
Hospitalized RTI due to RSVb
An RTI due to RSV that results in hospitalization
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Table 1.
Primary and Secondary Endpoint Events and Definitions in Infant 
Participants
Study 
Endpoints/Assessments
Study Definitions
Severe MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥70 bpm for <2 months of age [<60 days of age], 
≥60 bpm for ≥2 months to <12 months of age, or ≥50 bpm for 
≥12 months to 24 months of age) OR

SpO2 <93% OR

High-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive) OR

ICU admission for >4 hours OR

Failure to respond/unconscious 
AND

RSV-positive test result as described in Section 8.1.1.1
Protocol-defined primary 
endpoint

Any MA-LRTI or severe MA-LRTI due to RSV as determined by an 
EAC
Abbreviations: bpm = breaths per minute; EAC = endpoint adjudication committee; ICU = intensive care 
unit; MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically attended 
respiratory tract illness; NAAT = nucleic acid amplification technology; RR = respiratory rate; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness; SpO2 = oxygen saturation.
a.
RSV-positive testing is defined as a positive RSV test (see Section 8.1.1.1) conducted on a sample 
obtained during the medically attended visit or within 10 days (where Day 1 is the day of the MA-RTI 
visit) as detailed in Section 8.11.7.
b.
The EAC will determine if the endpoint criteria have been met upon review of the site source 
documentation from the MA-RTI visit and RTI study visits, including all available RSV test results.
Study Objectives – Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants 
born to maternal 
participants receiving 
1 dose of investigational 
product, the percentage 
of participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

AEs from birth to 1 month of age.

SAEs and NDCMCs:
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants 
enrolled during the first year of 
the study).
Secondary Efficacy Objectives
–
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI due to 
RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs 
from vaccination up to 730 days after 
birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 6 months 
of age.
MA-LRTIs due to RSV occurring 181 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after 
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV in infants after 6 months 
of age.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI in infants after 
6 months of age.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
To assess the impact of 
RSVpreF on RSV illness based 
on socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
To assess the effect of RSVpreF 
on healthcare utilization.
Univariate summaries of healthcare 
utilization variables, which may include 
the following: number and type of 
medical visits, length of hospital stay, 
requirement for mechanical ventilation, 
requirement for respiratory diagnostic 
procedures, requirement for IV fluids, 
requirement for prescriptions, and 
antibiotic use.
3.2. Maternal Participants
The study objectives and endpoints for maternal participants employ the event definitions in 
Table 2.
Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
Maternal medically attended visit
The maternal participant reports a visit with a healthcare 
provider (eg, outpatient or inpatient visit, emergency room, 
urgent care, or home visit)
MA-RTI visit maternal participant
A medically attended visit AND 1 or more of the following 
RTI signs and symptoms:

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
Abbreviations: MA-RTI = medically attended respiratory tract illness; RTI = respiratory tract illness.
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Study Objectives – Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimands
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery study 
visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum neutralizing 
titers and prefusion F IgG titers 
measured:

before vaccination.

at delivery.
3.3. Protocol-Defined Efficacy Endpoints 
All infant participants experiencing an MA-RTI will have an RTI study visit as detailed in
Section 8.1.  This protocol will use an independent EAC to determine whether certain 
investigator-reported events meet the definition of disease-related efficacy endpoints, using 
predefined endpoint criteria as summarized in Table 1. Members of this EAC will be blinded 
to the vaccine assignment to allow for unbiased assessments.
Recognizing that RSV disease is a dynamic illness, sites will be instructed to submit all 
available source documentation for adjudication from the MA-RTI visit and to record data 
from the worst day of illness in the electronic case report form (eCRF).  The EAC will 
determine if the endpoint criteria have been met upon review of the site source
documentation from the MA-RTI visit, including data collected at the RTI study visit, and all 
available RSV testing.  Further information about the EAC will be detailed in the 
adjudication charter, including specific descriptions of the scope of its responsibilities and 
the process and definitions to review and assess study endpoints.
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition and 
constitute a study endpoint will not be recorded as AEs.  For those AEs that are handled as 
disease-related efficacy endpoints, a data monitoring committee (DMC) will conduct 
unblinded reviews on a regular basis throughout the trial (see Data Monitoring Committee,
Section 9.5.1).
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Nonendpoint events (eg, an event that is determined not to be an MA-RTI) must be evaluated 
for safety reporting as per the protocol requirements.  Any AE that is adjudicated by the EAC
to not meet any endpoint criteria will be reported back to the investigator site of incidence; 
the investigator at the site must evaluate the event for safety as described in Appendix 2 of 
this protocol.  If the event is classified as serious, the investigator’s SAE awareness date in 
this instance is identified as the date on which the investigator site receives the nonendpoint 
SAE back from the EAC.  Handling these SAEs in this manner will allow Pfizer to meet its 
sponsor reporting obligations to regulatory authorities upon receipt of such SAEs.
Any events that remain unadjudicated at the annual safety report cutoff date will not be 
included in the safety tables of the report.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons. 
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of 
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis (Section 9.2). There is no specific case target for the 
additional primary endpoint of severe MA-LRTI. The total enrollment number of maternal 
participants may vary depending on the incidence rate of the primary endpoint in the infant 
participants, true underlying VE, and a potential early stop for efficacy or futility. In the 
event that efficacy in the infant population is demonstrated at the interim analysis, enrollment 
of maternal participants may continue in order to obtain safety evaluations in an adequate 
number of maternal and infant participants to support vaccine registration with national 
health authorities. Enrollment will be monitored to ensure even distribution of vaccination 
across gestational age between 24 0/7 and 36 0/7 weeks.
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It is anticipated that approximately 
6900 mother-infant pairs may be needed to accumulate 124 per-protocol cases.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF for this study will be 
120 µg (60 µg A and 60 µg B).
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Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term RTI 
surveillance and safety oversight to address safety and the possibility of conferred enhanced 
protection (antibody persistence) during a second RSV season. 
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. In addition, this study will use an 
E-DMC to monitor vaccine safety and efficacy and study futility.
4.1.1. Approximate Duration of Participation for Each Participant
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on GA at the time of vaccination and when the infant is 
actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth. 
4.1.2. Approximate Number of Participants
Healthy pregnant women will be randomly assigned to a study intervention. It is anticipated 
that approximately 6900 mother-infant pairs may be needed to accumulate 124 per-protocol 
cases as defined in Section 9.2 of the protocol. Enrollment will be monitored to ensure that 
participants will be recruited from both the northern and southern hemispheres. Enrollment 
may vary depending on the incidence in the placebo group, the true underlying VE, the 
dropout rate, and a potential early stop for VE or futility.
4.2. Scientific Rationale for Study Design
Refer to Section 2.1.
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4.3. Justification for Dose
The final dose and formulation of RSVpreF selected for use in this study is based on the 
safety and immunogenicity data from the ongoing C3671003 maternal immunization study
(A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093) and the first-in-human (FIH) study C3671001.
The FIH study was designed to describe the safety, tolerability, and immunogenicity of 
6 RSVpreF candidates with bivalent formulations (RSV A and B) at 3 escalating dose levels 
of 60 µg (30 µg A and 30 µg B), 120 µg (60 µg A and 60 µg B), and 240 µg (120 µg A and 
120 µg B) of the RSV prefusion F antigen, with or without Al(OH)3, when administered 
alone or concomitantly with seasonal inactivated influenza vaccine.  The study utilizes a 
sentinel cohort (N=168; Phase 1) and an expanded cohort (N=1014; Phase 2).  Nonpregnant 
female and male study participants of 2 age groups, 18 through 49 years of age and 
50 through 85 years of age, were enrolled into both cohorts.  The age groups are being run in 
parallel. 
An interim analysis of participants 18 through 49 years of age, including safety and 
tolerability (n=533) and immunogenicity (n=513) data up to 1 month after vaccination in the 
expanded cohort and additional immunogenicity data up to 3 months after vaccination in the 
sentinel cohort, has shown the RSVpreF candidate to be immunogenic and well tolerated. 
Local reactions and systemic events were noted to be predominantly mild or moderate across 
all doses and formulations, which is consistent with the current safety profile. The safety 
results from this planned interim analysis of healthy male and nonpregnant female 
participants 18 through 49 years of age are consistent with those from the sentinel-cohort 
analysis and indicate that RSVpreF has an acceptable safety profile and is well tolerated.
The immunogenicity results showed that RSVpreF elicited neutralizing titer geometric mean 
fold rises (GMFRs) of 10 to 20, 1 month after vaccination, depending on the formulation. 
Similarly, across all dose levels, with and without Al(OH)3, RSVpreF elicited high 
1-month-postvaccination RSV A and RSV B neutralizing GMTs. Overall, RSVpreF elicited 
anti–prefusion F immunoglobulin G1 (IgG1) responses that paralleled the elicited 
RSV-neutralizing responses. The ratio of RSV 50% neutralizing antibody titer GMFRs to 
prefusion RSV F binding IgG1 titer GMFRs (calculated with combined data for subgroups A 
and B) for the sentinel and expanded 18 through 49 years of age cohorts combined ranged 
from 0.62 to 0.76. The IgG1 and neutralization responses were similar in antigen-level dose
response, in equivalence of RSV A titer GMFRs to RSV B titer GMFRs, and in a lack of 
effect of Al(OH)3. 
Safety data for 403 mother/infant pairs, from maternal participants through 1 month after
maternal vaccination and for their infants from birth through the first month of life, in 
Study C3671003 provide further evidence of the safety of RSVpreF in maternal vaccine 
recipients, and initial evidence of the safety of maternal vaccination with RSVpreF for the 
infant. In maternal participants, solicited symptoms were generally mild to moderate in 
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intensity and of short duration. Unsolicited AEs were consistent with anticipated events in 
this participant population and did not indicate any differences between RSVpreF and control 
recipients. No differences in pregnancy (eg, reports of preterm delivery or obstetric 
complications) and birth outcomes (eg, reports of respiratory distress at delivery or presence 
of congenital anomalies) were observed between RSVpreF and control recipients. No 
differences in the number or types of AEs reported were observed between infants born to 
mothers receiving RSVpreF and those receiving placebo in the first month of life.
The high ratio of RSV-neutralizing antibody titer GMFRs to prefusion F–binding titer 
GMFRs elicited by Pfizer’s RSVpreF candidate indicates that most of the elicited antibody 
can neutralize the virus. It is assumed that this reflects the ability of the antibodies to prevent 
RSV disease in immunized participants and, in the case of maternal immunization, prevent 
disease in their infants.
The primary mechanism for protection of infants by the RSV maternal vaccine is 
neutralization of the virus by transplacentally transferred antibody, which is increased by 
immunization.  Maternal antibody decays exponentially in infants.  Therefore, it is 
anticipated that higher titers of transferred neutralizing antibodies will provide greater levels 
and durations of infant protection.  Results from the C3671001 FIH trial were used to 
determine the doses and formulations that are currently under investigation in the Phase 2b 
maternal immunization study: 120 µg or 240 µg of RSVpreF with or without Al(OH)3. 
These doses are expected to provide the greatest potential level of transplacental antibody 
transfer to infants and, therefore, the greatest potential benefit.  The dose and formulation of 
RSVpreF for the Phase 3 study was determined by the evaluation of the 1-month safety, 
tolerability, and immunogenicity results from the C3671003 maternal Phase 2b trial,
including infant RSV-neutralizing titers at birth.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last infant participant in the 
study. The study may also be terminated earlier for efficacy or futility as described in
Section 9.5.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1. Inclusion Criteria
5.1.1. Inclusion Criteria – Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply 
(refer to the investigator site file [ISF] for further eligibility details regarding region-specific 
timing of vaccination with respect to RSV seasonality and maternal gestational age at 
vaccination):
Note: In countries/locales where study procedures used to determine eligibility criteria 
(eg, ultrasound examination, human immunodeficiency virus [HIV] testing, syphilis testing) 
are not performed as part of routine prenatal care, they must be performed as part of this 
clinical trial and reviewed by the investigator or qualified designee within 28 days prior to 
randomization.  Maternal participants must provide informed consent prior to 
performing any procedures, including those that are being done exclusively to meet 
study eligibility criteria.
Note: Country-specific modifications associated with the study eligibility criteria are 
documented in Appendix 7, Appendix 8, and Appendix 9.
Age and Sex:
1. Healthy women ≥18 and ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of 
gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, 
who are at no known increased risk for complications. 
Note: GA must be based upon 1 of the following composite criteria based on timing and 
availability of data on the last menstrual period (LMP) and an ultrasound examination 
performed in the first or second trimester.30  The earliest ultrasound data available during 
the current pregnancy should be used:
a.
First-trimester data available (data obtained at ≤13 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a first-trimester ultrasound examination.

If there is a discrepancy of >5 days between the LMP-determined GA and an 
ultrasound result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA 
should be determined using the first-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and an 
ultrasound result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, 
then the GA should be determined using the first-trimester ultrasound result.
b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a second-trimester ultrasound result.
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
If there is a discrepancy of >7 days between the LMP-determined GA and the 
ultrasound result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >10 days between the LMP-determined GA and the 
ultrasound result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >14 days between the LMP-determined GA and the 
ultrasound result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
Type of Participant and Disease Characteristics:
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Receiving prenatal standard of care based on country requirements.
4. Had an ultrasound examination performed at ≥18 weeks of pregnancy with no significant 
fetal abnormalities observed, based on the investigator’s judgment. 
5. Determined by medical history, physical examination, and clinical judgment to be 
appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) 
surface antigen test during this pregnancy and prior to randomization (Visit 1). 
7. Intention to deliver at a hospital or birthing facility where study procedures can be 
obtained. 
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol OR
If the maternal participant is illiterate, a thumbprinted informed consent must be 
obtained, which must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process confirming that the maternal participant 
has been informed of all pertinent aspects of the study.
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5.1.2. Inclusion Criteria – Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a 
thumbprinted informed consent must have been obtained, which must have been signed 
and dated by an impartial witness who was present throughout the entire informed 
consent process confirming that the maternal participant/parent(s)/legal guardian(s) has 
been informed of all pertinent aspects of the study for herself (maternal participant) and 
her fetus/infant prior to taking part in the study.
Note: Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements. 
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
5.2. Exclusion Criteria 
5.2.1. Exclusion Criteria – Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not 
available, the BMI at the time of the first obstetric visit during the current pregnancy may 
be used.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any related 
vaccine.
4. Current pregnancy resulting from in vitro fertilization.  Participants known to have used 
clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are 
permitted.
5. Current pregnancy complications or abnormalities at the time of consent that will 
increase the risk associated with the participation in and completion of the study, 
including but not limited to the following:

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.
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
Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated
hypothyroidism.  This also includes disorders of glucose intolerance (eg, diabetes 
mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if 
uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the 
investigator’s judgment, that will increase the risk associated with the participation in and 
completion of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks’ gestation.

Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or significant congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the maternal 
or infant participant’s participation in, and completion of, the study or could preclude the 
evaluation of the maternal participant’s response (includes positive serologic testing for 
regional endemic conditions assessed during routine maternal care, as per local standards 
of care and obstetric recommendations).
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment.
9. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to 
consent and/or during study participation.
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11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of 
systemic corticosteroids for >14 days within 28 days prior to study enrollment.  
Prednisone use of <20 mg/day for ≤14 days is permitted. Inhaled/nebulized, 
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
12. Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an illicit 
drug for study eligibility.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before 
investigational product administration, or planned receipt through delivery, with 
1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt 
during study participation.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
5.2.2. Exclusion Criteria – Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and if no other exclusion criteria are met.  
The prevaccination blood draw and vaccination should take place on the same day. In the 
event that this is not possible, the prevaccination blood draw is also permissible within 7 days 
before the vaccination visit.

Current febrile illness (body temperature ≥38°C [≥100.4°F]) or other acute illness within 
48 hours before investigational product administration.

Diagnosed malaria within the last 7 days prior to investigational product administration.

Receipt of any inactivated vaccine within 14 days or any live vaccine within 28 days 
before investigational product administration.
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
If systemic corticosteroids (equivalent of ≥20 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical 
study but are not subsequently randomly assigned to investigational product. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs.
Maternal participants who do not meet the criteria for participation in this study (screen 
failure) may be rescreened. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
For this study, the investigational product(s) are RSVpreF and placebo (lyophile match).
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine 
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.  The
RSV drug product will be 120 µg of the RSV prefusion F antigen.  The drug product is 
supplied as a lyophilized white cake in a 2-mL glass vial, with a 13-mm lyophilization 
stopper, aluminum overseal, and flip-off cap. The drug product will be reconstituted by a 
diluent consisting of sterile water in a prefilled syringe (PFS). The lyophilized drug product 
contains excipients that, after reconstitution, will yield a solution as detailed in the IB.
The fill volume of the drug product vial and diluent PFS are designed such that the intended 
vaccine dose is delivered by injecting the entire contents of the syringe.
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6.1.2. Placebo
Placebo will be a lyophile match to the vaccine, which will consist of excipients matched to 
those used in the RSVpreF vaccine formulation, minus the active ingredients. 
The physical appearance of the reconstituted RSVpreF and placebo will be matched, and the 
study will be conducted in a double-blinded manner.
The fill volume of the placebo vial and diluent PFS is designed such that the intended 
placebo dose is delivered by injecting the entire contents of the syringe.
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
6.1.3. Administration
Maternal participants will receive 1 dose of investigational product at the vaccination visit 
(Day 1) in accordance with the study’s SoA.  The investigational product will be 
administered intramuscularly by injecting the entire contents of the syringe into the deltoid 
muscle, preferably of the nondominant arm, unless medically contraindicated, in which case 
the injection may be administered in the dominant arm. Investigational product
administration will be performed by appropriately designated study staff at the investigator 
site.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance. 
Investigational product administration details will be recorded on the case report form (CRF).
6.1.4. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluent for the 
investigational product (RSV vaccine or placebo). The investigational product supplies are 
provided in a kit that contains the investigational product (RSV vaccine or placebo 
lyophilized powder in a vial), a prefilled syringe containing sterile water, and a vial adapter.
Instructions for medical device use are provided in the investigational product manual 
(IP manual).
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Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the study personnel throughout the study.
Please refer to Section 8.3.9 for details. 
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention, as applicable for 
temperature-monitored shipments. 
2. Only maternal participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking days must indicate the minimum and maximum 
temperature since previously documented for all site storage locations upon return to 
business.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  All study interventions will be 
accounted for using an investigational product accountability form/record.
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
6. Study interventions should be stored in their original containers and in accordance with 
the labels.
7. See the IP manual for storage conditions of the study intervention once reconstituted.
8. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use of 
the study intervention after the temperature excursion. Use of the study intervention prior 
to Pfizer approval will be considered a protocol deviation. Specific details regarding the 
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definition of an excursion and information the site should report for each excursion will 
be provided to the site in the IP manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
Additional details about accountability, storage, destruction, and excursion reporting can 
be found in the IP manual.
6.2.1. Preparation and Dispensing
Refer to the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
Investigational product and placebo will be prepared by qualified site personnel according to 
the IP manual.  The investigational product will be administered only to maternal participants 
who are blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Blinding of Study Site Personnel 
This study is a double-blinded study, as the physical appearance of RSVpreF and placebo 
will be matched. The maternal participant, investigator, study coordinator, and all site staff 
will be blinded.
Please refer to the IP manual for further details.
6.3.2. Blinding of the Sponsor
The sponsor study team members will be blinded throughout the study to the vaccine 
assignments of all participants enrolled in the study. 
Laboratory personnel performing the serology and virology assays will remain blinded to 
vaccine assigned/received throughout the study.
6.3.3. Allocation to Investigational Product
Allocation of maternal participants to vaccine groups will proceed through the use of an 
interactive response technology (IRT) system (interactive Web-based response [IWR]).  The 
site personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the maternal participant number.  The site personnel will then be 
provided with a vaccine assignment, randomization number, and dispensable unit (DU) or 
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container number as investigational product is being supplied via the IRT system.  The IRT 
system will provide a confirmation report containing the maternal participant number, 
randomization number, and DU or container number assigned. The confirmation report must 
be stored in the site’s files. 
Note: Maternal participants will be randomized to a vaccine group as described above.  The 
infants of the maternal participants will be manually assigned an infant participant number at 
birth.
Investigational product will be dispensed and administered at study Visit 1 summarized in 
the SoA. 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Maternal participants will be assigned to receive investigational product according to the 
randomization scheme.  Investigators will remain blinded to the investigational product 
assigned to each maternal participant throughout the course of the study.
6.3.4. Breaking the Blind 
The study will be maternal participant and investigator blinded.
At the initiation of the study, the investigator will be instructed on the method for breaking
the blind for an individual participant.  The method will be an electronic process.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the participant.  The 
investigators should make every attempt to contact a member of the sponsor’s study team 
prior to breaking the blind.  When the blinding code is broken, the reason must be fully
documented and entered on the CRF.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy 
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal Participants

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study.

Receipt of blood/plasma products or Ig, from 60 days before investigational product 
administration, or planned receipt through delivery, with 1 exception, Rho(D) immune 
globulin (eg, RhoGAM), which can be given at any time.
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
Immunosuppressive therapy is prohibited during the course of the study.

Nonstudy vaccines may not be given concomitantly with the investigational product or 
within 7 days after investigational product administration (Day 1 to Day 7), except if 
medically necessary (eg, during an outbreak or pandemic situation).

Note: Licensed Tdap, may not be coadministered with the investigational product or 
given within 14 days after investigational product administration (Day 1 to Day 14), 
except if medically necessary (eg, during an outbreak- or pandemic-related situation).
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal Participants

Licensed vaccines (including influenza vaccine, tetanus toxoid, and tetanus diphtheria 
vaccines) may be given during the study starting 7 days after investigational product 
administration (Day 8), with the exception of licensed Tdap, which may be given starting 
14 days after investigational product administration (Day 15) as detailed in Section 6.5.1.

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. Short-term systemic corticosteroid (equivalent of <20 mg/day of prednisone)
use for ≤14 days prior to the administration of investigational product is permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during participant participation in the 
study.
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following vaccinations and treatments for maternal participants would require reporting 
in the CRF during the study: 

Details of any vaccinations given at any time during the pregnancy through the final 
study visit will be collected and recorded in the CRF.

Details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given to the maternal participant at any time during the 
pregnancy or during the study will be collected and recorded in the CRF.

Any prescribed medications taken to treat medically attended respiratory illnesses from 
enrollment until the final study visit will be recorded in the CRF.
Concomitant medications not meeting the criteria above will be assessed but not documented 
on the CRF.
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6.5.4. Prohibited Concomitant Vaccinations and Treatments – Infant Participants

Investigational vaccines, drugs, nutritional products, or medical devices are prohibited 
during the course of the study.
6.5.5. Permitted Concomitant Vaccinations and Treatments – Infant Participants

ONLY routine treatments, routine vaccinations, and routine procedures 
(eg, circumcision) are permitted at any time during the study, in accordance with national 
recommendations, medical standard of care, or accepted practice.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during infant participant participation in the study.

Local anesthetic may be applied to the site of the blood draw, as appropriate.
6.5.6. Recording Nonstudy Vaccinations and Concomitant Medications – Infant 
Participants
The following CRF reporting guidelines are applicable to treatments given to infant 
participants during the study:

Details of any Ig (including monoclonal antibodies [eg, Synagis] or immune globulin 
[eg, hepatitis B immune globulin (HBIG)]) or blood products (eg, whole blood, packed 
cells) given to the infant participant will be collected from the time of birth until the final 
study visit and recorded in the CRF.

Any prescribed medication taken to treat medically attended respiratory illnesses from 
the time of birth until the final visit.

Details of IV fluids given during an MA-RTI will be collected and recorded in the CRF.
6.6. Dose Modification
Dose modification is not applicable in this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Discontinuation of study intervention is not applicable in this study.
7.2. Participant Discontinuation/Withdrawal From the Study
A maternal participant may withdraw from the study at any time at her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. An infant participant may withdraw from the study at 
any time at the request of his or her parent(s) and/or legal guardian(s) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.
The participants, or, if appropriate, their parent(s) and/or legal guardian(s), should be
questioned regarding their reason for withdrawal. The participant will be permanently
discontinued from the study at that time.
If a maternal participant withdraws from the study, she may request destruction of any 
remaining samples taken and not tested, but data already generated from the samples will 
continue to be available and may be used to protect the integrity of existing analyses. If an 
infant participant is withdrawn from the study, his or her parent(s) and/or legal guardian(s) 
may request destruction of any remaining samples, but data already generated from the 
samples will continue to be available, and may be used to protect the integrity of existing 
analyses. The investigator must document any such requests in the site study records and 
notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
Participants who withdraw after randomization will not be replaced.
7.3. Withdrawal of Consent
Maternal participants and parent(s)/legal guardian(s) of infant participants born to maternal 
participants who request to withdraw consent from any further study contact or with persons 
previously authorized by the participant to provide this information should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible.  The withdrawal of consent should be explained in detail in the medical records by 
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the investigator, as to whether the withdrawal is only from study procedures and/or 
postvaccination study follow-up. If the participant (maternal or infant) only withdraws from 
a study procedure, safety information should be completed until the end of the study, unless 
consent for further contact has been withdrawn.  In the event that vital status (whether the 
participant is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
The regulatory and ethical considerations for this study, including the informed consent 
process, are summarized in Section 10.1.1 and Section 10.1.3.
7.4. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant, or parent(s) and/or legal guardian(s), and 
reschedule the missed visit as soon as possible and counsel the participant or parent(s) 
and/or legal guardian(s) on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or parent(s) and/or legal guardian(s) wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record.

Should the participant or parent(s) and/or legal guardian(s) continue to be 
unreachable, the participant will be considered to have withdrawn from the study.
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
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Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the maternal participant’s routine clinical 
management and obtained before signing of the ICD may be utilized for baseline 
purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA and protocol.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
8.1. Efficacy Assessments
8.1.1. Efficacy Assessments – Infant Participants
MA-RTIs in the infant participant will be identified from 72 hours after the infant’s delivery 
until the end of the infant’s participation in the study.  If the infant participant meets any RTI 
criteria listed below that require a visit by or a visit to an HCP (outpatient or inpatient visit, 
emergency room, urgent care, or scheduled home visit), an RTI study visit by the study staff 
will be required (see Section 8.11.7).
The RTI criteria are if the infant experiences 1 or more of the following respiratory signs or 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any duration

Cough

Inability to feed for any duration due to respiratory symptoms
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
Apnea

Any other respiratory symptom of concern 
Evaluation of these MA-RTI events will be based on predefined clinical signs and symptoms 
and testing criteria (shown in Table 1) obtained at the medically attended visit with the 
healthcare provider and/or the study visit. These events will be assessed and confirmed to be 
contributing to the study endpoints by an independent EAC as per the protocol.
8.1.1.1. Midturbinate Nasal Swab Collection and Testing Requirements for Endpoint 
Confirmation – Infant Participants
Midturbinate nasal swabs will be collected for RSV analyses from infant participants at each 
RTI study visit during the RSV surveillance period from birth until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of MA-LRTI during the RTI surveillance
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). The swabs
will be sent to Pfizer for centralized reverse transcription–polymerase chain reaction 
(RT-PCR) testing.
RSV testing performed locally as part of routine care will be considered valid when analyzed 
under the following conditions:  

Nucleic acid amplification technology (NAAT)-based test result positive for RSV was 
obtained using a Food and Drug Administration (FDA)-cleared assay.

AND

NAAT-based test result was obtained in a laboratory that is currently Clinical Laboratory 
Improvement Amendments (CLIA)-certified or has the equivalent US 
certification/accreditation (eg, College of American Pathologists [CAP]) or the equivalent 
ex-US certification as outlined in the adjudication charter. 
Note: Rapid antigen-based test results will not be considered for endpoint assessment.
Study samples should be collected as close to the medical visit as possible and preferably 
within 72 hours of the MA-RTI visit. Study samples positive for RSV by RT-PCR as 
defined above will count toward the endpoint definition when collected for up to 10 days 
after the MA-RTI, where Day 1 is the day of the MA-RTI visit. These results will be used 
for MA-RTI endpoint definition and confirmation as detailed in Table 1.
8.1.1.2. Events for Adjudication and Submission Guidance – Infant Participants
To maintain scientific integrity, this protocol will use an EAC for the adjudication of all 
efficacy endpoints as summarized below.  The EAC will remain blinded to the maternal 
participants’ vaccine assignments, and the EAC’s assessment of these events will represent 
the final confirmed endpoint classification of the event. 
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The efficacy-related events for adjudication include all MA-RTI events. The study 
definitions for endpoint events and the MA-RTI adjudication criteria for the EAC, including 
roles and responsibilities, are specified in the endpoint adjudication committee charter 
(EACC). 
The identification of an MA-RTI will be made by the investigational site and communicated 
to Pfizer or its designee. However, these MA-RTI events may also be identified by Pfizer or 
its designee during the review of clinical data listings or by site monitors during routine 
monitoring of the infant participants’ study records. Pfizer or its designee will notify the 
investigational site of any events identified during this process.
The EAC is responsible for adjudicating whether MA-RTI events fulfill the protocol-defined 
clinical criteria as a primary endpoint, whether the event was due to RSV based on 
confirmatory testing, and the severity of the illness (eg, MA-RTI, MA-LRTI, or severe 
MA-LRTI).  The EAC will adjudicate all RSV-positive MA-RTI cases through the active 
follow-up period including all cases occurring up to 180 days after birth. The EAC will 
adjudicate severe manifestations of RSV: all RSV-associated cases of hospitalization and 
severe MA-LRTI. All deaths during the study are to be reported to Pfizer Safety upon 
awareness. 
The Pfizer study team or designee will provide a listing of specific documents needed to 
support endpoint adjudication by the EAC. These documents will be detailed in the EACC
and the ISF.  Obtaining and submitting the documentation, including results of local testing 
for RSV, will be the responsibility of the investigational site. Documentation will vary based 
on the potential endpoint requiring adjudication and may include (but not be limited to) 
emergency room visit records, hospital discharge summaries, clinic and/or progress notes, 
diagnostic tests, pathology reports, autopsy reports, and death certificate information, as 
applicable.
Pfizer may request that additional cases of interest be reported to the committee in addition to 
those listed above, including cases in which RSV testing is indeterminant or otherwise 
unclear. Cases that are determined to be RSV positive using non–NAAT-based clinical 
testing can be adjudicated, explored, and summarized descriptively.
8.1.2. Exploratory Efficacy Assessments – Maternal Participants
An MA-RTI will be identified from vaccination until the end of the study and will contribute 
to an exploratory endpoint for maternal participants.  The definition and assessment criteria 
as described in Section 8.10.6 include a visit by or to a healthcare provider (outpatient or 
inpatient visit, emergency room, urgent care, or home visit) for any symptoms in the RTI 
criteria as detailed in Table 2.
The maternal participant should contact the study staff immediately but no later than the next 
scheduled visit to report RTI signs and symptoms for which she sought medical attention. 
The procedures as detailed in Section 1.2.3.1 and Section 8.10.6 will be required to capture 
the event in the CRF.
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8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal and Infant 
Participants
Infant MA-RTI events that are consistent with the clinical and endpoint definitions for infant 
participants should not be recorded as AEs. These data will be captured as efficacy 
assessment data only, as these are expected endpoints.
For maternal participants, MA-RTI events that are consistent with the clinical and endpoint 
definition will be captured as detailed in Section 8.1.2 and will not be recorded as AEs.
Any event that the investigator has judged to have a causal relationship with the 
investigational product or to have resulted in death MUST be reported to Pfizer Safety as 
described in Appendix 2, even if that event is a component of an endpoint.
8.1.4. Immunogenicity Assessments
8.1.4.1. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be approximately 30 mL (~15 mL/visit).
8.1.4.2. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical 
Consideration for Clinical Trials Performed in Children.31
All infants will have a cord blood sample collected at birth. The cord blood is collected from 
the umbilical cord vein attached to the placenta after the umbilical cord has been clamped 
and cut. Blood should be collected as soon as feasible after birth to minimize coagulation 
and maximize volume. The total volume of cord blood to be collected for antibody 
assessment in this study will be 10 mL. 
If cord blood is unavailable, a blood sample may be collected from the infant participant up 
to 7 days after birth but preferably within 24 hours after birth.  The infant’s weight must 
be used to determine the volume of blood that can be collected (see Table 3).
A blood sample will be collected from the infant participant only if a cord sample is not
obtained. In the event that a sample is collected, the volume of blood will vary depending on 
the infant’s weight. 
The maximum volume of blood collected from the infant in the absence of cord blood will be 
no more than 5 mL.
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Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained
Body Weight (in kg)
Approximate Volume of Blood (in mL) 
to Be Collected 
<1.3
No blood draw
1.3 to ≤2.4
1.0
>2.4 to ≤3.7
2.0
>3.7 to ≤4.9
3.0
>4.9 to ≤6.2
4.0
>6.2
5.0
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant Participants
Maternal sera (prevaccination/time of delivery) and infant cord blood collected will be 
assayed for RSV A and RSV B serum neutralizing titers and anti-RSV prefusion F IgG 
levels. Maternal sera collected may be tested for Ig levels against nonvaccine RSV antigens
to assess natural RSV exposure.
RSV A and RSV B serum neutralizing titers will be determined and reported as the 
neutralizing titer. IgG levels will be determined against both RSV A and RSV B prefusion F 
antigens in a direct-binding Luminex immunoassay (dLIA) and reported as an anti–
prefusion F IgG level.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development – Maternal and Infant Participants
Samples remaining after completion of the planned assays from blood draws or infant 
respiratory nasal swab specimens taken throughout the study may be used for additional 
vaccine and infectious disease related research. Samples may also be used for assay 
development, standardization, qualification, and validation.  This work is critical in the 
development, qualification, and validation of serological assays and is required by regulatory 
authorities for their use in the licensure of a vaccine.
8.1.4.5. Respiratory Pathogens – Infant Participants
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI
visit during the RSV surveillance period from birth until Visit 3, and for all hospitalizations 
due to an RTI and severe cases of MA-LRTI during the RTI surveillance period from 
Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). 
Samples will be analyzed for RSV A, RSV B, and other respiratory pathogens by polymerase 
chain reaction (PCR)-based assays at a central laboratory. Additional exploratory analyses 
may also be performed.
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Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.6. Biological Samples – Maternal and Infant Participants
Samples will be used only for scientific research.  Each sample will be labeled with a code so 
that the laboratory personnel testing the samples will not know the maternal or infant
participant’s identity.  Samples that remain after performing assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.  If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No sequencing of the maternal or infant participant’s DNA will be performed. 
The maternal participant may request that her (or her infant’s) samples, if still identifiable, be 
destroyed at any time; however, any data already collected from those samples will still be 
used for this research.  The biological samples may be shared with other researchers as long 
as confidentiality is maintained, and no testing of the maternal and infant participant’s DNA 
is performed.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
Safety parameters will be assessed as described in the SoA and below for both maternal and 
infant participants.
8.2.1. Participant Electronic Diary – Maternal Participants
All maternal participants vaccinated in the study will be observed for at least 30 minutes after 
investigational product administration for any acute reactions. For all maternal participants, 
prespecified local reactions and systemic events will be collected for 7 days after vaccination.
Maternal participants will be required to use an electronic diary (e-diary), installed on a 
provisioned device or as an application on a personal device, and will be asked to monitor 
and record local reactions, systemic events, and temperature each evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  Prior 
to vaccination, a baseline assessment of prespecified systemic events will be recorded in the 
e-diary.
The e-diary allows recording of these assessments only within a fixed time window each day, 
thus providing the accurate representation of the maternal participant’s experience at that 
time.
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If the maternal participant is illiterate, a study staff/field worker may visit the maternal 
participant in her home or contact her via phone daily after vaccination to assess and record 
local reactions, systemic events, and temperature each day (beginning in the morning) for 
6 days following vaccination (Day 2 through Day 7). Maternal participants may call the site 
and report additional local reactions and systemic events at any time during the Day 1 to 
Day 7 reporting period.  The study staff/field worker will be required to record these data on 
a provisioned device or an application on a personal device, thus providing the accurate 
representation of the maternal participant’s experience at that time.  For events persisting at 
Day 7 and use of antipyretic medication continuing at Day 7, the field worker will continue 
to visit the participant and record information until resolution.
Data on local reactions, systemic events, and temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via an internet-based 
portal.  At intervals agreed to by the vendor and Pfizer, these data will be transferred 
electronically to Pfizer for analysis and reporting.  These data do not need to be recorded by 
the investigator in the CRF, except the following conditions:

If a maternal participant withdraws because of prompted events recorded in the e-diary, 
the event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF. 
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate maternal participant compliance and as part of the 
ongoing safety review. These prospectively collected occurrences of local reactions and 
systemic events are graded as described in Section 8.2.1.1 and Section 8.2.1.2.
8.2.1.1. Local Reactions – Maternal Participants
Following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), the 
maternal participants/study staff member/field worker will be asked to assess redness, 
swelling, and pain at the injection site and to record the symptoms in the e-diary or 
appropriate device, in the evening or daily based on local practice.
Redness and swelling will be measured by the maternal participant/study staff/field worker 
and recorded in measuring device units (range: 1 to 20 and 21+) and then categorized during 
analysis as mild, moderate, or severe based on the grading scale in Table 4. Measuring 
device units can be converted to centimeters according to the following scale: 1 measuring 
device unit = 0.5 cm.
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A maternal participant with severe redness, swelling, or pain at the injection site will be 
prompted to contact the investigator to perform an unscheduled visit to assess the reaction or 
will be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate.  In the event that the maternal participant
does not call, the investigator or qualified designee will contact the maternal participant.
Only an investigator or a qualified designee is able to classify a maternal participant’s local 
reaction as Grade 4, after clinical evaluation of the maternal participant or documentation 
from another medically qualified source (eg, emergency room or hospital record) or, in the 
case of pain at the injection site only, contact with the maternal participant. If a maternal 
participant experiences a Grade 4 local reaction, the investigator must immediately notify the 
sponsor.  A Grade 4 reaction will be collected as an AE on the CRF.  The event will be 
graded using the AE intensity grading scale (Section 10.2.4).
The site staff/field worker will educate the maternal participant regarding signs and 
symptoms that would prompt site contact.
If a local reaction persists beyond the end of the e-diary period, the maternal participant will 
be requested to report that information and/or any new AEs that develop to the investigator,
or the study staff/field worker will continue to call or visit the maternal participant to assess
and record the information until resolution, as per local practice. The investigator will enter 
this additional information in the maternal participant’s source notes and CRF.
Table 4.
Grading Scale for Local Reactions
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 
20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 
20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis
Pain (at the 
injection site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a maternal participant’s local reaction as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
contact with the maternal participant.  Grade 4 local reactions will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
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8.2.1.2. Systemic Events – Maternal Participants
Prior to vaccination on Day 1, a baseline assessment of fatigue, headache, vomiting,
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e-diary. Following 
vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), maternal 
participants will be asked to assess fatigue, headache, vomiting, nausea, diarrhea, muscle 
pain, and joint pain and to record the symptoms in the e-diary in the evening or, based on 
local practice in certain countries/locales, a study staff member/field worker will call or visit 
maternal participants daily after vaccination to assess the presence of systemic events each 
day (beginning in the morning) for 7 days following vaccination (Day 1 through Day 7, 
where Day 1 is the day of vaccination).  The study staff member/field worker will record the 
symptoms in the e-diary daily. The symptoms will be assessed by the maternal participant 
according to the grading scale in Table 5.  Maternal participants will also be instructed to 
contact site staff if they visit the emergency room or are hospitalized for severe fatigue, 
headache, vomiting, nausea, diarrhea, muscle pain, or joint pain within 7 days after 
vaccination. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as appropriate. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant. The 
study staff/field worker may also contact the maternal participant to obtain additional 
information on events entered into the e-diary.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic 
event as Grade 4, after clinical evaluation of the maternal participant or documentation from 
another medically qualified source (eg, emergency room or hospital record) or contact with 
the maternal participant.  If a maternal participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.  Grade 4 reactions will be collected as an 
AE on the CRF.  The event will be graded using the AE intensity grading scale 
(Section 10.2.4).
Further, if a systemic event persists beyond the end of the e-diary period, the maternal 
participant will be requested to report that information and/or any new AEs that develop to 
the investigator, or the study staff/field worker will continue to call or visit the maternal 
participant to assess and record the information until resolution, as per local practice. The 
investigator will enter this additional information in the maternal participant’s source notes 
and CRF.
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Table 5.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness in 
diaries)
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Headache
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Vomiting
1 to 2 times in 24 hours
>2 times 
in 24 hours
Requires 
intravenous 
hydration
Emergency room 
visit 
or hospitalization 
for severe 
vomiting
Nausea
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe nausea
Diarrhea
2 to 3 loose stools
in 24 hours
4 to 5 loose stools
in 24 hours
6 or more loose 
stools
in 24 hours
Emergency room 
visit
or hospitalization 
for severe diarrhea
Muscle pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe muscle pain
Joint pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe joint pain
a.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic event as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the maternal participant.  Grade 
4 systemic reactions will be collected on the AE case report form and assessed by the investigator using 
the AE intensity grading scale as detailed in Section 10.2.4.
8.2.1.3. Temperature – Maternal Participants
A digital thermometer will be given to the maternal participant with instructions on how to 
measure oral temperature at home in degrees Celsius.  Temperature will be collected in the 
evening for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination) and at any time during the 7 days following vaccination that fever is suspected. 
Similarly, based on local practice in certain countries/locales, the study staff/field worker will 
call or visit maternal participants daily for 6 days after vaccination (Day 2 through Day 7, 
where Day 1 is the day of vaccination) to collect the temperature.
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Fever is defined as an oral temperature of ≥38.0°C (≥100.4°F). The highest temperature for 
each day will be recorded in the e-diary, where possible. In certain countries/locales, if a 
temperature of ≥38.0°C (≥100.4°F) is recorded for a maternal participant during the 
collection of diary events after vaccination, the study staff/field worker will perform a rapid 
test for malaria as per local practice.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature less than 38.0°C [100.4°F]) in order to 
collect a stop date in the CRF. 
A maternal participant with a fever >38.9°C (>102.0°F) will be prompted to contact the 
investigator. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns, as applicable. In the event that the maternal participant 
does not call, the investigator or qualified designee will contact the maternal participant.  The 
investigator or qualified designee will assess the fever and perform an unscheduled visit as 
appropriate.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as 
Grade 4, after clinical evaluation of the maternal participant, documentation from another 
medically qualified source (eg, emergency room or hospital record), or contact with the 
maternal participant.  Grade 4 fevers will be collected on the AE CRF and assessed by the 
investigator using the AE intensity grading scale as detailed in Section 10.2.4.
Temperature will be measured and recorded to 1 decimal place and then categorized during 
analysis as mild, moderate, or severe based on the intensity grading scale provided in
Table 6.
Table 6.
Ranges for Fever
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fever
≥38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°C
a.
Only an investigator or qualified designee is able to classify a maternal participant’s fever as Grade 4, 
after clinical evaluation of the maternal participant, documentation from another medically qualified 
source (eg, emergency room or hospital record), or contact with the maternal participant.  Grade 4 fevers 
will be collected on the AE case report form and assessed by the investigator using the AE intensity 
grading scale as detailed in Section 10.2.4.
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant Participants
There are no protocol-required laboratory assessments.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
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The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 4.  Device deficiencies are covered in Section 8.3.9.
AEs will be reported by the maternal participant/parent(s)/legal guardian(s).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7).
Each maternal participant and parent/legal guardian/legally authorized representative of an 
infant participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
Maternal Participants
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each maternal participant including her fetus begins from the time the maternal 
participant provides informed consent, which is obtained before participation in the study 
(ie, before undergoing any study-related procedure and/or receiving investigational product), 
through and including a minimum of 28 calendar days after the last administration of the 
investigational product.
In this study, the investigator and site staff will ensure the active elicitation and collection of 
safety events as detailed below:

The active collection period for nonserious AEs begins once informed consent has been 
provided and continues through a minimum of 28 calendar days after vaccination.

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

In addition, AEs occurring up to 48 hours after blood draws that are related to study 
procedures must be reported in the CRF.

Details of any MA-RTI will not be collected as AEs/SAEs from informed consent until 
the maternal participant completes the study, unless the investigator or an appropriate 
designee deems the event to be possibly related to the investigational product or to have
resulted in death as detailed in Section 8.1.2 and Section 8.1.3.
For maternal participants who are screen failures, the active collection period ends when 
screen failure status is determined.
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Infant Participants
For the infant participant, the time period for actively eliciting and collecting safety events is 
detailed below:

The active collection period for nonserious AEs begins at birth and continues through and 
including a minimum of 28 calendar days after birth. 

The active collection period for NDCMCs and SAEs begins at birth and continues 
through the last study visit. 
o
Details of any MA-RTI will not be collected as AEs/SAEs from 72 hours after 
birth until the infant participant completes the study, unless the investigator or an 
appropriate designee deems the event to be possibly related to the investigational 
product or if the event resulted in death. See Section 8.1 for the reporting 
procedures for efficacy-related endpoints. Note: Details of the MA-RTI visit 
should be recorded in the eCRF.

In addition, AEs occurring up to 48 hours after blood draws or nasal swabs that are 
related to study procedures must be reported in the CRF.
For Both Maternal and Infant Participants
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For maternal participants, and parent(s)/legal guardian(s) of infant participants born to 
maternal participants, who withdraw from the study and withdraw consent for the collection 
of future information, the active collection period ends when consent is withdrawn. 
If a participant definitively discontinues or temporarily discontinues study intervention
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form.
Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the Vaccine SAE Reporting Form. 
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the Vaccine SAE Reporting Form, immediately upon awareness and under no 
circumstances should this exceed 24 hours.
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If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy; 
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those that occur within 1 month after birth; or congenital 
anomaly* [in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal 
death]), the investigator should follow the procedures for reporting SAEs.  In addition, infant 
deaths after 1 month of age should be reported as SAEs.
Further follow-up may be requested by the sponsor and will be handled on a case-by-case 
basis (eg, follow-up on preterm infants to identify developmental delays).
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety. 
The same is applied for those SAEs after the active collection period has ended, should they 
occur to the fetus.  In addition, infant deaths that occur after 12 months of age should be 
reported as SAEs when the investigator believes the SAE or death has at least a reasonable 
possibility of being related to investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.32
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All AEs/SAEs occurring in a participant during the active collection period, which begins 
after obtaining informed consent as described in Section 8.3.1, will be recorded on the AE 
section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant and parent(s)/legal guardian(s) of infant 
participants born to maternal participants.
The investigator obtains general information on the pregnancy and its outcome for all study 
participants.  The investigator will follow the pregnancy until completion (or until pregnancy 
termination).  In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth.  In the event of a termination, the reason(s) for termination should be 
specified and, if clinically possible, the structural integrity of the terminated fetus should be 
assessed by gross visual inspection (unless preprocedure test findings are conclusive for a 
congenital anomaly and the findings are reported).
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If the outcome of the pregnancy meets the criteria for an SAE (ie, stillbirth, neonatal death,
defined as those deaths that occur within 1 month after birth; or congenital anomaly* [in a 
live-born baby, a stillbirth, or a neonatal death]), the investigator should record this 
information in the CRF.  In addition, infant deaths after 1 month of age should be recorded in 
the CRF as SAEs. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
*Further guidance on the identification and classification of congenital anomalies (structural 
and developmental), including genetic syndromes for this study, can be found in the ISF and 
is based on the Metropolitan Atlanta Congenital Defects Program.32
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.4).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 2.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
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Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
Potential efficacy endpoints on this study as defined in Section 8.1 will be excluded from the 
standard SAE reporting process unless deemed possibly related to investigational product.
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the 
Investigational Product
8.3.5.1. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Scenarios of exposure during breastfeeding for infants not delivered during the study must be 
reported, irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours 
of the investigator’s awareness, using the Vaccine SAE Reporting Form.  An 
exposure-during-breastfeeding report is not created when a Pfizer drug specifically approved 
for use in breastfeeding women (eg, vitamins) is administered in accord with authorized use.  
However, if the infant experiences an SAE associated with such a drug’s administration, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.2. Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
investigational product, which may or may not lead to the occurrence of an AE. Such 
persons may include HCPs, family members, and other roles that are involved in the trial 
participant’s care.
Note: This does NOT apply to maternal participants enrolled in this trial.
In addition, the scenarios below describe environmental exposures that could lead to an 
exposure during pregnancy (EDP): 

A female becomes or is found to be pregnant, having been exposed (eg, because of 
environmental exposure) to the investigational product; or the female becomes or is 
found to be pregnant after being exposed to the investigational product;

A male has been exposed (eg, because of environmental exposure) to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy. 
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An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the Vaccine SAE Reporting Form and the Exposure During Pregnancy 
Supplemental Form, as applicable, regardless of whether there is an associated SAE.  In the 
event of an EDP, the information submitted should include the anticipated date of delivery.  
Since the information does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the ISF.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
are as follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.
8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
This section provides information on adverse events of special interest (AESIs) that may be 
detected during the study.
For infant participants:33

Preterm birth (born at <37 weeks’ gestation)

Birth weight 1001 to 2500 g

Developmental delay
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The following AESIs are to be reported as SAEs:

Extremely preterm birth (<28 weeks)

Extremely low birth weight (≤1000 g)
For maternal participants:

Preterm delivery with cause, if available
All AESIs must be reported as an AE or SAE following the procedures described in
Section 8.3.1 through Section 8.3.4. An AESI is to be recorded as an AE or SAE on the 
CRF. In addition, an AESI that is also an SAE must be reported using the Vaccine SAE 
Reporting Form.
8.3.8.1. Lack of Efficacy
This section is not applicable for this study, as efficacy is yet to be demonstrated in the study 
population.
8.3.9. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 4.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 2 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 4.
8.3.9.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  Follow-up applies to all participants, including 
those who discontinue study intervention.
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The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
Information will be provided to the sponsor as described in the IP manual. 
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
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Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration by an incorrect route;

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any additional dose of investigational product will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose in the CRF.
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4. Overdose is reportable to Safety only when associated with an SAE.
No interruptions or dose modifications will be made in this study. 
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Health Economics
Health economics will be evaluated in exploratory analyses assessing vaccine impact on 
healthcare resource utilization parameters evaluated during study visits, which may include 
the following: number and type of medical visits, length of hospital stay, requirement for 
mechanical ventilation, requirement for respiratory diagnostic procedures, requirement for IV 
fluids, requirement for prescriptions, and antibiotic use. 
8.10. Procedures – Maternal Participants 
8.10.1. Screening and Vaccination Visit (Clinic; 28 Days Prior to Vaccination to Day 1 –
Visit 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant. Each signature on the 
ICD must be personally dated by the signatory.
Maternal participants who might be illiterate must thumbprint the ICD and it must be signed 
and dated by an impartial witness who was present throughout the entire informed consent 
process before performing any study-related procedures.
The investigator or his or her designee will also sign and date the ICD.  A copy of the 
signed/thumbprinted and dated ICD must be given to the maternal participant.  The source 
data must reflect that the informed consent was obtained before participation in the 
study.
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If the maternal participant is found ineligible for the study based on a full assessment of 
inclusion and exclusion criteria, the investigator may advise the participant, either by 
telephone or face to face, that the participant will be excluded from further participation in 
the study, as defined in Section 5.4.  All eligible maternal participants will proceed to 
complete the vaccination visit.
Standard-of-care procedures performed prior to informed consent can be considered for use 
in the study provided they follow guidance around the timing of procedures stipulated in the 
protocol.
In countries/locales where procedures to confirm maternal participant eligibility for
this clinical trial are not routinely performed, the procedures must be obtained and 
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.
The following procedures will be performed:

Obtain written informed consent from the maternal participant before performing any 
study-specific procedures. If the maternal participant is illiterate, she must thumbprint 
the ICD and it must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity).  The date of birth will be 
collected to critically evaluate the immune response and safety profile by age.

Obtain and record current/former alcohol, tobacco, marijuana, or any illicit drug usage.

Obtain and record any medical, surgical, and obstetric history of clinical significance 
including history from prior and current pregnancy(ies).

Record the LMP and estimated delivery date (EDD).

Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.

Record the prepregnancy BMI in the source documentation. If the prepregnancy BMI is 
not available, record the BMI at the time of the first obstetric visit during the current 
pregnancy. 
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
Perform targeted physical examination evaluating/noting any clinically significant 
abnormalities within the following body systems: general appearance; skin; head, eyes, 
ears, nose, and throat; heart; lungs; abdomen; musculoskeletal; extremities; neurological; 
and lymph nodes.  Significant medical and surgical history and abnormal observations 
from the physical examination will be documented and recorded in the CRF.

Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement.
o
Where an obstetric ultrasound examination is not performed at ≥18 weeks of 
pregnancy as part of prenatal standard of care, perform an ultrasound examination.
o
Note: Physical or obstetric examinations performed as standard of care may be 
admissible if performed within 7 days prior to the vaccination visit.

Obtain details of any Ig (including monoclonal antibodies or immune globulin [Rho(D) 
immune globulin, eg, RhoGAM]) or blood products (eg, whole blood, packed cells) given 
at any time during the current pregnancy.

Obtain details of any nonstudy vaccinations given at any time during the current 
pregnancy.

Obtain details of syphilis, HIV, and HBV status.

Note: Only participants with a documented negative syphilis test result and negative 
HIV antibody and HBV surface antigen test results obtained during the current 
pregnancy are eligible for randomization. 

If not performed as standard of care, assessment should be performed as part of the 
study, locally, and vaccination of maternal participant should be deferred until the 
results are available and confirmed to be negative within 28 days prior to study 
randomization.

Ensure and document that all the inclusion criteria and none of the exclusion 
criteria are met.

Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.2.3.

Issue the maternal participant an e-diary and provide instructions on its completion
(if applicable).

Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures, and provide instructions on their use.
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
On the day of and prior to vaccination, ask the maternal participant to capture the 
baseline systemic event measurements in her e-diary or the site staff will capture the 
baseline systemic event measurements in the provisioned device (if applicable for 
illiterate participants).

Prior to vaccination, collect a blood sample of approximately 15 mL for serologic 
assessments (prevaccination blood collection should take place on the same day or within 
7 days before the vaccination visit).

Obtain the maternal participant’s randomization number and investigational product kit 
number using the IRT system. Refer to the IRT manual for further instructions on this 
process.

Qualified site staff member(s) will administer a single-vial dose of investigational 
product into the deltoid muscle of the (preferably) nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
Please refer to the IP manual for further instruction on this procedure.

Site staff must observe the maternal participant for any acute reactions for at least 
30 minutes after investigational product administration.

Record any acute reactions in the maternal participant’s source documents, on the AE 
page of the CRF, and on the Vaccine SAE Reporting Form as applicable.

Ask the maternal participant to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination, OR explain to the maternal participant that a study staff 
member/field worker will call or visit her every day from Day 2 to Day 7 after 
vaccination (where Day 1 is the day of vaccination) to collect or take her temperature and 
record systemic events, acute local reactions, and use of antipyretic medication in a diary
(if applicable).

Ask the maternal participant to contact the site staff or investigator immediately if she 
experiences any of the following from Day 1 to Day 7 after vaccination to determine if an 
unscheduled reactogenicity visit is required as detailed in Section 8.10.5 OR inform the 
maternal participant that if she experiences any of the following from Day 1 to Day 7 
after vaccination or is taking antipyretic medication at Day 7, then the study staff/field 
worker will continue to visit until resolution.  Furthermore, the maternal participant will 
be referred to the appropriate healthcare facility at the discretion of the study staff/field 
worker if there are any concerns as detailed in Section 8.10.5.

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring >20 measuring device units 
(greater than 10 cm).
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
Severe pain at the injection site.

Any severe systemic event.

Inform the maternal participants that if a temperature of ≥38.0°C (≥100.4°F) is recorded 
during the collection of diary data, she will be required to have a rapid test for malaria as 
per local practice and details will be recorded in the diary (if applicable, based on local 
practice).

Remind maternal participants that study staff may contact them to obtain additional 
information on events entered into the e-diary.

Remind maternal participants to inform the study staff of any AEs and SAEs that occur 
for the duration of the trial as described in Section 8.2 and Section 10.2.

Remind the maternal participant to bring the completed e-diary to the next visit
(if applicable). 

Complete the source documents.

The investigator or an authorized designee completes the CRFs and the blinded 
dispenser/administrator completes the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6.

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit (The study staff/field worker will contact the maternal participant prior 
to the next study visit to remind her, if applicable).
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After Vaccination)
If delivery occurs before this visit, this visit will not be conducted.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.
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
Review the participant’s e-diary data. Collect stop dates of any e-diary events ongoing 
on the last day that the e-diary was completed and record stop dates in the CRF.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2. Note: Active 
elicitation and collection of AEs and SAEs through 28 days after vaccination must occur 
even if delivery occurs within 28 days after vaccination.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6. 

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit (The study staff/field worker will contact the maternal participant prior 
to the next study visit to remind her, if applicable).
8.10.3. Delivery (Maternity Unit)
The delivery visit spans the time from when a participant is admitted in labor through 
discharge following delivery of her infant. Protocol-specified procedures associated with 
this delivery visit may be done at any time during this period.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

If available, record the maternal participant’s group B streptococcal (GBS) status and if 
any medication was given for intrapartum antibiotic prophylaxis (IAP). Note: Positive 
GBS carriage should not be reported as an adverse event in the CRF if performed in the 
setting of routine prenatal care.

Record details of any nonstudy vaccinations given since the last visit.
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
Collect a blood sample of approximately 15 mL for serologic assessments.  Note: The 
maternal participant’s blood sample can be taken at any time during the delivery visit, 
preferably before delivery. In the event that the blood sample cannot be obtained 
before delivery, the sample should be collected as close to delivery as possible and at 
most 48 hours postpartum.
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments 
must also be collected.  Cord blood is collected from the umbilical cord vein attached to 
the placenta prior to the blood clotting within the cord and after the umbilical cord has 
been clamped and cut.  This sample should be labeled with the infant’s participant ID 
number.

Record pregnancy outcome information, including vital status of the infant (live, 
stillbirth, etc), mode of delivery (vaginal delivery or cesarean section), and the use of any 
assisted devices (forceps or vacuum).

Record details of any MA-RTI, including the diagnosis. 

Record AEs as described in Section 8.2 and Section 10.2.

Ask the maternal participants to contact the site to report any significant illness (new or 
worsening), any medically attended respiratory events (eg, doctor’s visit, emergency 
room visit), or any hospitalization that occurs during the study period as detailed in 
Section 8.10.6.

Ask the maternal participant to contact the site staff or investigator if her newborn infant 
meets the MA-RTI study criteria OR the study staff/field worker will contact the 
maternal participant/legal guardian(s) weekly to remind them to report any MA-RTI 
(if applicable).

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.4. 6-Month-Postdelivery Visit (Clinic, Home, or Telephone; 180 to 210 Days After 
Delivery)

Obtain details of any postnatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [eg, HBIG]) or Rho(D) immune globulin [eg, RhoGAM]) or blood 
products (eg, whole blood, packed cells) given since the last visit.

Record details of any nonstudy vaccinations given since the last visit.

Record details of any MA-RTI, including the diagnosis.
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
Ask the maternal participant to contact the site staff or investigator if her infant meets the 
MA-RTI study criteria OR the study staff/field worker will contact the maternal 
participant/legal guardian(s) weekly to remind them to report any MA-RTI, if applicable.

Record AEs as described in Section 8.2 and Section 10.2.

Complete the maternal participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.5. Unscheduled Reactogenicity Visits
If the maternal participant reports 1 or more of the following, a contact must occur as soon as 
possible between the maternal participant and the investigator, or a medically qualified 
member of the study site staff, to assess if an unscheduled reactogenicity visit is required OR
based on local practice in certain countries/locales, maternal participants will be referred to 
the appropriate healthcare facility at the discretion of the study staff/field worker if there are 
any concerns regarding reactogenicity events, including:

redness at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

swelling at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

severe injection site pain on the arm that the investigational product was 
administered, 

fever ≥39.0°C (≥102.1°F).
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The maternal participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or

The participant/study staff/field worker recorded an incorrect value in the e-diary 
(confirmation of an e-diary data entry error), or

The investigator or appropriate designee determines that the visit is not required.
This contact will be recorded in the maternal participant’s source notes and in the CRF.
Any ongoing reactions must be assessed at the next scheduled visit.
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The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure oral temperature.

Measure the participant’s heart rate.

Measure the participant’s blood pressure (seated).

Measure the minimum and maximum diameters of redness (if present) on the arm in 
which the investigational product was administered.

Measure the minimum and maximum diameters of swelling (if present) on the arm in 
which the investigational product was administered.

Assess if necrosis is present at the injection site on the arm in which the investigational 
product was administered.

Assess if any exfoliative dermatitis is present.

Assess any injection site pain on the arm in which the investigational product was 
administered that is present in accordance with the reactogenicity grading scale provided 
in Section 8.2.1.1.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 8.2.1.2.

Ask the participant if she attended an emergency room visit or was hospitalized.

For severe pain at the injection site resulting in an emergency room visit or 
hospitalization, severe systemic events associated with an emergency room visit or 
hospitalization, any necrosis on the arm in which the investigational product was 
administered, or exfoliative dermatitis, the investigator or qualified designee must assess 
these events in accordance with the intensity AE grading scale provided in
Section 8.2.1.1 and Section 8.2.1.2.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

Complete the participant’s source documents.

The investigator or an authorized designee will complete the CRFs.

The study staff/field worker may contact the participant to obtain additional information 
on events entered into the e-diary, as appropriate.
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8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria – Maternal 
Participants

Starting from Day 1 after vaccination (where Day 1 is the day of vaccination) until the 
end of the study, all maternal participants will be monitored for MA-RTIs as detailed in 
Section 1.2.3.1 and Section 8.1.2. Maternal participants should notify the site and/field 
worker of the occurrence of any MA-RTIs immediately but no later than the next study 
visit. Note: Site contact may be by an electronic method of communication (including 
but not limited to electronic messaging, short message service [SMS], text, email), by 
phone call, or by face-to-face contact.

The definition of maternal RTI includes 1 or more of the following signs and/or 
symptoms:
o
New or increased sore throat
o
New or increased cough
o
New or increased nasal congestion
o
New or increased nasal discharge
o
New or increased wheezing
o
New or increased sputum production
o
New or increased shortness of breath

Record the details of any MA-RTI, including the diagnosis, the medically attended visit 
location (hospital, outpatient visit, emergency room, urgent care, or home visit), duration 
of hospitalization, intensive care unit (ICU) duration if applicable, prescribed medications 
for the MA-RTI, assessments including RSV test result (eg, NAAT, rapid antigen 
detection tests, or any other molecular diagnostic test), if available, and the final 
diagnosis.

Record the details of any nonstudy vaccinations.

Record AEs as described in Section 8.2 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.11. Procedures – Infant Participants
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After Birth)

Manually assign a single infant participant identifier. This will be assigned manually by 
the site using the following convention: the infant participant’s identifier will be the 
maternal participant’s IRT-generated numeric ID but with the fifth digit changed to a 2 
(eg, if the maternal participant is given number 10011001, then the infant will be 
10012001).

Collect a cord blood sample of approximately 10 mL for immunogenicity assessments.  
Cord blood is collected from the umbilical cord vein attached to the placenta prior to the 
blood clotting within the cord and after the umbilical cord has been clamped and cut.  
This sample should be labeled with the infant’s participant ID number.

If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 24 hours, but up to 7 days after birth.  The volume of blood collected 
will be based on the weight of the infant (refer to Table 3).

Ensure and document that all the infant inclusion criteria and none of the infant exclusion 
criteria are met.

Collect demography (including complete date of birth [ie, dd-Mmm-YYYY], sex, race, 
and ethnicity).  The date of birth will be collected to critically evaluate the immune 
response.

Obtain and record the infant’s length, head circumference, and weight at birth.

Obtain and record the infant’s birth data, including GA and appearance, pulse, 
grimace, activity, and respiration (Apgar) score. 

Obtain and record background factors as described in Section 10.5.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.

Standard-of-care vital signs and examination procedures can be considered for use in 
the study provided they were performed within 48 hours after birth. Note: Please 
reference the physical examination procedures below for details. 

Perform a physical examination, if not performed as part of standard of care, noting 
any clinically significant abnormalities within the following body systems: general 
appearance; skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; back; 
musculoskeletal; extremities; genitourinary; neurological; and lymph nodes.  
Abnormal results must be recorded on source documents as well as the physical 
examination pages of the CRF; only if the abnormal finding is deemed to be clinically 
significant should this be recorded on the AE pages of the CRF. 
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
Record details of any congenital anomalies on the AE page of the CRF, and report 
as an SAE as described in Section 10.2.3.

Record any medication as described in Section 6.5.6.

Obtain details of any Ig (including monoclonal antibodies [eg, Synagis] or immune 
globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given to the 
infant participant since birth.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Review the weekly contact schedule with the parent(s)/legal guardian(s) and collect 
contact information OR remind the parent(s)/legal guardian(s) that a field worker will 
contact them weekly to remind them to report any MA-RTI (if applicable).

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria. An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11.2. Visit 2 – 1-Month Follow-up (Clinic or Home, 28 to 48 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of this study visit.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate. Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the
study visit.
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
Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the site source documents. Newly 
identified abnormal findings must be recorded on source documents and, if considered 
clinically significant in the judgment of the investigator/examiner, on the AE page of the 
CRF. Note: Standard-of-care examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee 
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria.  An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.7.1.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every 7 days 
from birth until the 6-month follow-up visit to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The weekly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.7.1 for guidance on reported cases of 
MA-RTIs in infant participants during the first 6 months after birth. 
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8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic or Home, 180 to 210 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 
Note: Standard-of-care measurement procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.

Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.
Note: Standard-of-care examination procedures can be considered for use at this study 
visit, if they were performed within the window of the study visit.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Ask the parent(s)/legal guardian(s) to contact the investigator immediately if any 
significant illness or hospitalization occurs or if the infant meets the MA-RTI visit
criteria.  An RTI study visit, along with a nasal swab collection, must be performed 
for all hospitalizations due to an RTI and severe MA-LRTIs as described in 
Section 1.2.4.1 and Section 8.11.8.
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
If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care as 
described above, noting any clinically significant abnormalities in the source documents. 
Newly identified abnormal findings must be recorded on source documents and, if 
considered clinically significant in the judgment of the investigator/examiner, on the AE 
page of the CRF. Only applicable if a clinic visit is conducted. Note: Standard-of-care 
examination procedures can be considered for use at this study visit, if they were 
performed within the window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants except for infant participants born during the first year of the study.

The investigator or an authorized designee completes the CRF for infant participants born 
during the first year of the study. Note: An additional 12-month blinded follow-up period 
for longer-term RTI surveillance and safety oversight will be included for these 
participants.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Confirm the understanding of the infant participant’s parent(s)/legal guardian(s) 
regarding site contact for the study, which is approximately every month (28 to 35 days) 
until the end-of-study visit. Ask the parent(s)/legal guardian(s) to contact the 
investigational site/field worker promptly if the infant meets the MA-RTI visit criteria.  
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The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days After Birth; 
Infant Participants Born During the First Year of the Study Only)

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 
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
Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.

If medically necessary (eg, during an outbreak, pandemic situation, or natural 
disaster), review the nasal swab collection and shipping instructions with the infant’s 
caregiver to ensure he/she acknowledges understanding of requirements as detailed in 
Section 8.11.8.
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 742 Days After 
Birth; Infant Participants Born During the First Year of the Study)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if 
a clinic visit is conducted). Note: Standard-of-care measurement procedures can be 
considered for use at this study visit, if they were performed within the window of the 
study visit.

Perform a targeted physical examination, if not performed as part of routine care, noting 
any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF. 
Only applicable if a clinic visit is conducted. Note: Standard-of-care examination 
procedures can be considered for use at this study visit, if they were performed within the 
window of the study visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents. 

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants born during the first year of the study.
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8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 Months After 
Delivery)

This is an active surveillance period spanning from birth through 6 months after delivery 
(Visit 3). Note: Reporting MA-RTI events should commence 72 hours after the infant’s 
delivery.  Respiratory distress events associated with and within 72 hours of birth should 
not be captured as MA-RTI events for the study but should be captured as AEs/SAEs 
(if applicable).

The sponsor may alter the frequency of the weekly contacts or the duration of 
surveillance for MA-RTI based on RSV surveillance data or other operational factors.
8.11.7.1. Study Visits Following a Medically Attended RTI – Hospital, Home, or Clinic 
Visit

Contact the infant participant’s parent(s)/legal guardian(s) approximately every week 
(7 to 10 days) from birth until Visit 3 (6-month follow-up visit), to remind the 
parent(s)/legal guardian(s) to contact the investigational site promptly if the infant meets 
the criteria for an MA-RTI event.  The weekly contact may be via the e-diary device or 
study-related mobile application, text, email, phone call, or face-to-face contact with the 
site staff/field worker. Please refer to Table 1 regarding clinical signs and symptoms that 
meet the study definition of an MA-RTI, and Section 1.2.4.1 for study-required 
assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by:
o
The infant caregiver during or within 10 days following the MA-RTI visit
OR
o
The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an event requiring a visit to a healthcare provider, the site staff 
and/field worker should confirm, based on information provided, whether the event meets 
the criteria for an MA-RTI. Please refer to Table 1 and Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

When an infant MA-RTI criterion is met or confirmed, the site/field worker will obtain 
records from the medically attended visit and record the healthcare information as 
detailed in Appendix 6.
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
When an infant MA-RTI criterion is met or confirmed, the infant participant will be 
seen as soon as possible and within 72 hours (preferable) or up to 10 days for an RTI 
study visit by the investigational site staff or qualified designee. 

The infant participant may be seen either at the time of the MA-RTI, at home or at the 
study site (if discharged), or if the infant participant has been hospitalized or is receiving 
treatment at another medical facility, the site staff/field worker can conduct the RTI study 
visit at those facilities.
o
If the RTI study visit is not performed within 72 hours of the event, it should still be 
performed, including the collection of nasal swab specimens. 
o
Targeted assessments at an RTI study visit include but are not limited to:
o
Respiratory signs: lower chest wall indrawing.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Nasal swab collection from the infant participant for testing at the central 
laboratory.
o
Body weight

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site/field worker if the infant’s 
illness worsens, or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for the event as detailed in Section 8.1.
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8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit Criteria

This is a long-term surveillance procedure for all infant participants from 6 months after 
delivery (Visit 3) until the last study visit.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) from Visit 3 (6-month follow-up visit) until the end-of-study visit, to 
remind the parent(s)/legal guardian(s) to contact the investigational site promptly if the 
infant meets the criteria for an MA-RTI visit.  The monthly contact may be via the 
e-diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: In the event that restrictions prevent taking RTI study swabs because of an 
outbreak, pandemic situation, or natural disaster, the study nasal swab can be collected 
for processing at a Pfizer central laboratory by: 
o
The infant caregiver during or within 10 days following the MA-RTI visit
OR
o
The HCP assessing the infant during the MA-RTI visit

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an MA-RTI, the site should obtain additional information and 
determine whether the event also meets the study definition of a severe MA-LRTI.
o
Note: Severe MA-LRTI is defined in Table 1.

The site/field worker will obtain records from the medically attended visit and record the 
healthcare information as detailed in Appendix 6.

When an infant MA-RTI criterion is confirmed and also meets the study definition of 
hospitalization due to an RTI or a severe MA-LRTI, the infant participant will be seen 
as soon as possible and within 72 hours (preferable) or up to 10 days for an RTI study 
visit that includes a nasal swab collection by the investigational site staff/field worker. 
The staff/field worker will obtain the nasal swab within 72 hours (preferable) or up to 
10 days of the event with the infant participant either at home (if discharged) or, if the 
infant participant has been hospitalized or receiving treatment at another medical facility, 
the site staff/field worker will conduct the visit at those facilities.
o
Note: Nasal swab collection from the infant participant is for testing at the central 
laboratory.
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
A targeted RTI study visit will be required for all reported cases of hospitalization due to 
an RTI or severe MA-LRTI only, and this includes but is not limited to:
o
Respiratory signs: lower chest wall indrawing, failure to respond/unconsciousness.
o
Vital sign assessment: temperature, respiratory rate, heart rate, and oxygen 
saturation by pulse oximetry. Note: It is recommended that the participant not be 
receiving supplemental oxygen at the time of measurement.
o
Body weight

A targeted RTI study visit is not required for an MA-RTI event not meeting the definition 
of hospitalization due to an RTI or severe MA-LRTI.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the MA-RTI event, including emergency room or
hospitalization details with admission and discharge date (if applicable).

Record any medication as described in Section 6.5.6.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.  Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site if the infant’s illness worsens, 
or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Compile the adjudication submission package for hospitalizations due to an RTI and 
severe MA-LRTI events only as detailed in Section 8.1.
8.12. Nasal Swab Collection
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI 
visit during the RSV surveillance period from 72 hours after delivery until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of an MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1).
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The nasal swab sample is to be collected as soon as possible and within 72 hours (preferred) 
or up to 10 days of an MA-RTI visit in either the infant participant’s home or a medical 
setting (eg, clinic, hospital, etc) by the investigational site staff. 
If medically necessary (eg, during an outbreak, pandemic situation, or natural disaster), the 
nasal swab can be collected by the infant’s caregiver or the HCP assessing the infant 
(in addition to any samples obtained in the course of routine clinical care) for processing at a 
Pfizer central laboratory, as detailed in Section 8.11.7.1 and Section 8.11.8.
In the event that these restrictions prevent taking RTI study swabs at the investigational site, 
the infant’s caregiver will be given a study nasal swab collection kit including shipping 
instructions, to be used if necessary. The infant caregiver or the HCP assessing the infant 
during an MA-RTI visit may assist the investigational sites by collecting of the study nasal 
swab samples, as required.
Note: Investigational site staff will review the procedures for nasal swab sample collection 
and shipping instructions with each infant caregiver and ensure that he/she understands the 
appropriate procedures for collecting and packaging samples for shipment to the study site.
The process for nasal swab collection and transport to the Pfizer central laboratory via study 
sites is detailed in the ISF.
8.13. Communication and Use of Technology
In a study of this duration that is event-driven, it is vital to ensure that communication 
between the study site and the maternal participant and parent(s)/legal guardian(s) is 
maintained to ensure that endpoint events are not missed.  This study will employ various 
methods, tailored to the individual participant (maternal and/or infant participant), to ensure 
that communication is maintained and study information can be transmitted securely.  Using 
appropriate technology, a communication pathway between the maternal participant and 
parent(s)/legal guardian(s) and the study site staff will be established.  The maternal 
participant and the parent(s)/legal guardian(s) may be able to utilize their own devices to 
access this technology, or use a device provided by the sponsor.  Traditional methods of 
telephone communication will also be available. The technology solution may facilitate the 
following:

Contact with the investigator.

The ability of the maternal participant/parent(s)/legal guardian(s) to report MA-RTI visits
associated with the infant participant.

An alert in the event that the maternal or infant participant is hospitalized.

Visit reminders.
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
Messages of thanks and encouragement from the study team.

A platform for recording local reactions and systemic events (e-diary).
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in an SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Estimands and Statistical Hypotheses
The null hypothesis to be tested concerns VE for the primary endpoints. The RSV vaccine 
will be compared to placebo, testing the hypotheses H0: VE ≤20% vs Ha: VE 20%. For all 
secondary efficacy endpoints, the RSV vaccine will be compared to placebo, testing the 
hypotheses H0: VE ≤0% vs Ha: VE >0%. Hypothesis testing of the secondary endpoints is 
conditional upon rejection of the null hypothesis for at least 1 of the primary endpoints.
9.1.1. Estimands – Infant Participants
9.1.1.1. Efficacy
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with key protocol criteria (evaluable participants): 

VE, defined as the percentage relative risk reduction in the incidence of MA-LRTI due to 
RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of severe MA-LRTI 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of hospitalization 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of all-cause 
MA-LRTI in the RSV vaccine group, relative to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  For participants who 
discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
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9.1.1.2. Immunogenicity
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with the key protocol criteria (evaluable participants):

Functional antibody levels estimated by the GMT for RSV A and RSV B serum
neutralizing titers.

Geometric mean ratio (GMR), estimated by the ratio of the GMTs for RSV A and RSV B
serum neutralizing titers of the RSV vaccine group to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as missing completely at random (MCAR) is assumed.  For participants 
who discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.3. Safety
In infant participants born to the maternal participants receiving 1 dose of investigational 
product:

The percentage of infant participants with specific birth outcomes.

The percentage of infant participants having AEs from birth through 1 month of age.

The percentage of infant participants having SAEs, NDCMCs, and new diagnosed 
congenital anomalies from birth through the last study visit.
Missing AE dates and missing AE intensity will be handled according to Pfizer safety rules.
9.1.2. Estimands – Maternal Participants
9.1.2.1. Immunogenicity
In maternal participants receiving 1 dose of investigational product and in compliance with 
the key protocol criteria (evaluable participants):

The immune response, estimated by the GMT for RSV A and RSV B serum neutralizing 
titers.

The immune response, estimated by the GMFR from baseline in RSV A and RSV B 
serum neutralizing titers.

GMR, estimated by the ratio of the GMTs for RSV A and RSV B serum neutralizing 
titers of the RSV vaccine group to the placebo group.
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
Geometric mean of the IgG levels against RSV prefusion F.

Geometric mean of the Ig levels to nonvaccine RSV antigens.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as MCAR is assumed.  For participants who discontinue from the study 
or have major protocol violations, all postdiscontinuation or postviolation observations will 
be censored.
9.1.2.2. Safety
In maternal participants receiving 1 dose of investigational product:

The percentage of maternal participants reporting AEs through 1 month after vaccination.

The percentage of maternal participants reporting obstetric complications and SAEs 
through the end of the study.

The percentage of maternal participants reporting local reactions within 7 days of 
vaccination.

The percentage of maternal participants reporting systemic events within 7 days of 
vaccination.
Missing e-diary data will not be imputed; missing AE dates and missing AE intensity will be 
handled according to Pfizer safety rules.
9.2. Sample Size Determination
This is an event-driven study. Sample size is determined as the number of participants to be 
randomized that is expected to accrue the required number of primary endpoint cases in the 
evaluable population. In this study there are 2 primary endpoints, and success on either 
primary endpoint is sufficient (see Section 9.1); power for the study overall is therefore at 
least as high as the power for either primary endpoint individually. In order for the study to 
have at least 90% power to reject the null hypothesis for MA-LRTI due to RSV when true 
VE is 60%, a total of 124 cases of MA-LRTI due to RSV within 90 days of birth are required 
in the evaluable population. This also accounts for potential use of an alpha of 1.25% 
1-sided within the multiplicity adjustment. There is no explicit case target for the endpoint of 
severe MA-LRTI due to RSV; depending on the assumed true VE, power for that individual 
hypothesis may be lower, but the power for the primary endpoint family will be at least 90%. 
Hypotheses about VE may be restated as hypotheses about the proportion of cases in the 
RSV vaccine group, conditional upon a fixed total number of cases. If this proportion is p, 
the null hypothesis H0: VE ≤20% is equivalent to H0: p ≥0.444; the assumption of VE = 60% 
corresponds to p = 0.286. Power was evaluated by the exact binomial test, and the case 
target established as that number k for which power is guaranteed to be at least 90%, for all 
k* ≥k. The calculation accounted for the study design (1:1 randomization of participants to 
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RSV vaccine : placebo), a single planned interim analysis of efficacy (see Section 9.5), and 
an overall type 1 error of 2.5% 1-sided across the 2 primary endpoints. 
This global study is planned to be conducted in the United States and other high-income 
countries as well as LMICs. Incidence rates of the primary endpoints are expected to vary in 
different regions. Based on a recently completed Phase 3 trial of an RSV vaccine, the 
assumed incidence rate for MA-LRTI due to RSV through 90 days in low-incidence 
countries, such as the United States, is approximately 1.75%; and in other regions,
approximately 3.90%. With these assumptions, and also allowing for 60% VE and 10% of 
enrolled participants being nonevaluable, enrollment of approximately 6900 participants is 
planned for the study as a whole. The exact number of participants required to accrue the 
case target may be higher or lower than this, depending on incidence rates, observed VE, and 
the proportion of participants evaluable.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined for infant and maternal 
participants:
Population
Description
Enrolled 
All maternal participants who sign the ICD.
Randomly assigned to 
investigational product
All maternal participants who are assigned a randomization 
number in the IRT system.
Evaluable efficacy –
infant (per-protocol)
All infant participants who are eligible, are born to the 
maternal participants who received the investigational product 
to which they were randomized at least 14 days prior to 
delivery, did not receive palivizumab or another monoclonal 
antibody targeting RSV, have valid and determinate results for 
the proposed analysis, and have no major protocol violations. 
Modified intent-to-treat 
(mITT) efficacy – infant
All infant participants who are born to vaccinated maternal 
participants and have valid and determinate results for the 
proposed analysis.
Evaluable 
immunogenicity – infant
All infant participants who are eligible, are born to the 
maternal participants who received the investigational product 
to which they were randomized, have blood drawn for assay 
testing within the specified time frame, have valid and 
determinate assay results for the proposed analysis, and have 
no major protocol violations. 
Evaluable 
immunogenicity –
maternal
All maternal participants who are eligible, receive the 
investigational product to which they were randomized, have 
blood drawn for assay testing within the specified time frame, 
have valid and determinate assay results for the proposed 
analysis, and have no major protocol violations. 
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Population
Description
mITT immunogenicity –
infant
All infant participants who are born to vaccinated maternal 
participants and have at least 1 valid and determinate assay 
result for the proposed analysis.
mITT immunogenicity –
maternal
All randomized maternal participants who receive 
investigational product and have at least 1 valid and 
determinate assay result for the proposed analysis. 
Safety – infant
All infant participants who are born to vaccinated maternal 
participants.
Safety – maternal
All randomized maternal participants who receive 
investigational product.
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock for the first planned analysis 
and will describe the participant populations to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data.  This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The analysis of efficacy will use a conditional exact test based on the 
binomial distribution of the number of disease cases in the RSV vaccine 
group, given the total number of cases in both groups. The incidence of 
MA-LRTI due to RSV and severe MA-LRTI due to RSV in infant 
participants will be evaluated in both groups up to 90 days, 120 days, 
150 days, and 180 days after birth.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population. 

The 2 primary endpoints of MA-LRTI due to RSV and severe 
MA-LRTI due to RSV will be tested in parallel using a multiplicity 
adjustment procedure. Success of the trial requires rejection of the null 
hypothesis (ie, a CI lower bound >20%) for either one of the 2 primary 
endpoints.

The primary endpoint of severe MA-LRTI due to RSV may be demoted 
to a secondary endpoint, if there are insufficient cases for an adequately 
powered analysis. During the trial, blinded accrual of cases will be 
monitored and prior to any unblinding, a decision rule for this change 
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will be established based on the total number of cases of severe 
MA-LRTI due to RSV.

Testing of the 2 primary endpoints across the time intervals will follow 
a fixed sequence with a gatekeeping strategy. First, the hypothesis 
pertaining to the incidence of the 2 primary endpoints within 90 days 
after birth will be tested, at the full multiplicity-adjusted alpha level, 
using a multiplicity adjustment for the 2 endpoints. If that null 
hypothesis cannot be rejected, testing ends. Otherwise, testing proceeds 
to the incidence within 120 days after birth. Only primary endpoint(s)
that are successful at all earlier time intervals will be considered at 
subsequent intervals. Testing will proceed to the endpoints evaluated at 
150 days and 180 days, conditional on rejection of the null hypotheses 
for all earlier time intervals. Refer to the SAP for full details of the 
testing sequence and multiplicity correction strategy.

There may be a single interim analysis of the MA-LRTI-due-to-RSV
endpoint when there is an adequate number of cases (at least half the 
target number within 90 days). Based on the fraction of cases included 
in the interim analysis, an alpha level will be derived based on a
Lan-DeMets implementation of the O’Brien-Fleming alpha spending 
function. For example, if there is a single interim analysis at exactly 
50% of the cases, the appropriate 1-sided significance levels are 0.0014 
at the interim analysis and 0.0245 at the final analysis. Implementation 
of these 1-sided significance levels ensures the overall type 1 error for 
the primary endpoint will be no more than 0.025. See Section 9.5 for 
more details.

At the interim analysis there will also be an assessment for futility, 
based on conditional power for the MA-LRTI-due-to-RSV endpoint. If 
the probability of success at the end of the trial is low, given the interim 
analysis results and the initially assumed VE is applied to the remaining 
data, consideration will be given to stopping the study for futility.

CIs for VE will be calculated using the appropriate multiplicity-adjusted 
alpha level α. If the lower 100(1 - α)% confidence limit for VE exceeds 
20%, the null hypothesis for that endpoint will be rejected.

At the end of the trial, the RSV vaccine may be deemed efficacious if 
there are 43 or fewer cases of MA-LRTI due to RSV in the RSV 
vaccine group out of the 124 total primary endpoint cases.  This 
corresponds to estimated VE = 47% with 95.1% CI = (22%, 64%). For 
severe MA-LRTI, assuming a total of 50 cases occur, the vaccine may 
be deemed efficacious if there are 14 or fewer cases in the RSV vaccine 
group.  This corresponds to estimated VE = 61% with 95.1% 
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CI = (26%, 81%). For both of these examples, it is assumed a 1-sided 
alpha of 0.0245 applies to the endpoint in question. A smaller 
multiplicity-adjusted alpha may apply, leading to a higher VE required 
for success. 

Kaplan-Meier curves showing accrual of primary endpoint cases over 
180 days will be presented.
Secondary

The analysis of secondary efficacy endpoints will use the exact 
conditional binomial method, as for the primary endpoint. Secondary 
endpoints will be examined at the final analysis only. VE will be 
estimated along with 2-sided 95% CI. 

Inference for the secondary endpoints will be conditional upon 
demonstrating success for one of the primary efficacy endpoints. The 
secondary endpoints of hospitalizations due to RSV and all-cause 
MA-LRTI will be tested in parallel so as to preserve the overall type 1 
error across primary and secondary endpoint families at no more than 
2.5% 1-sided. Multiplicity correction strategies will be defined in the 
SAP. VE for each secondary endpoint will be evaluated sequentially at 
90 days, 120 days, 150 days, and 180 days, as for the primary endpoint. 
Testing will only proceed to later time points conditional on success of 
all previous time points. 

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.
Exploratory

The incidence in infant participants of MA-RTIs due to RSV with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized.

The incidence in infant participants of MA-RTIs due to any cause with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized. All MA-RTIs and severe MA-LRTIs will be summarized 
separately.

The incidence in infant participants of MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The incidence in infant participants of severe MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized. 
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
The incidence in infant participants of hospitalization due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The primary endpoint through 180 days after birth will be summarized 
separately as cases associated with RSV subgroup A or RSV subgroup 
B infection.

The primary endpoint through 180 days after birth will be summarized 
by interval from vaccination to delivery and by GA at the time of 
vaccination.

The incidence of MA-RTI due to any cause in maternal participants 
from vaccination through 180 days after delivery will be summarized. 
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting 
each event for each vaccine group.

A 3-tier approach will be used to summarize AEs. For both Tier 1 and 
Tier 2 events, the 95% CIs for the difference in the percentage of 
participants reporting the events between the RSV vaccine group and the 
placebo group will be calculated using the test statistic proposed by 
Miettinen and Nurminen; in addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in the percentage of 
participants reporting the events, based on the same test statistic and 
under the assumption that the test statistic is asymptotically normally 
distributed.  A Medical Dictionary for Regulatory Activities (MedDRA) 
preferred term is defined as a Tier 2 event if there are 1% or more 
participants in at least 1 vaccine group reporting the event.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
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Secondary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting 
each event for each vaccine group.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Exploratory

These analyses will be described in the SAP, finalized before first 
database lock.
9.4.3. Other Analyses 
9.4.3.1. Immunogenicity Analyses
Immunogenicity endpoints are exploratory in the study.  The analyses of immunogenicity 
endpoints will be based on the evaluable populations.  An additional analysis will be 
performed based on the mITT populations if there is enough difference between the mITT 
populations and the evaluable populations.  Immunogenicity data for maternal participants 
and infant participants will be summarized separately, with the exception of maternal-to-
infant placental transfer analysis.  Participants will be summarized according to the vaccine 
group to which they (for maternal participants) or their mothers (for infant participants) were 
randomized.
The secondary and exploratory immunogenicity endpoints will be described by the following 
summaries and the 95% CIs:

GMT of the RSV A and RSV B serum neutralizing titers at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMT of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMFR for RSV A and RSV B serum neutralizing titers from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMFR of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).
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
GMR of the RSV vaccine group to the placebo group for the RSV A and 
RSV B serum neutralizing titers at each available time point after vaccination (maternal 
participants and infant participants, separately).

GMR of the RSV vaccine group to the placebo group for the combined RSV A/B serum
neutralizing titers at each available time point after vaccination (maternal participants and 
infant participants, separately).

Geometric mean of the IgG levels against RSV prefusion F and Ig levels to nonvaccine 
RSV antigens at each available time point by vaccine group (maternal participants and 
infant participants, separately).

Geometric mean of IgG subclass levels (minimally IgG1) against RSV prefusion F at 
each available time point by vaccine group (maternal participants only).
Empirical reverse cumulative distribution curves (RCDCs) for combinations of time points 
and vaccine groups will be presented for RSV A and RSV B serum neutralizing titers.
A sensitivity analysis will be performed to exclude immunogenicity data from mothers and 
their infants following onset of RSV infection between vaccination and delivery (based on 
evidence from the nonvaccine antigen assay). 
Subgroup analyses of the secondary and exploratory immunogenicity endpoints will be 
performed, including an analysis based on GA at the time of vaccination, time from 
vaccination to delivery, and by country subcategories. All subgroup analyses will be defined 
in the SAP.
In addition, the maternal-to-infant placental transfer ratio (infant/mother) of RSV A and 
RSV B serum neutralizing titers and associated 95% CI will be summarized.
9.4.3.2. Healthcare Utilization Analyses
Healthcare utilization endpoints are exploratory in the study; these analyses will be described 
in the SAP and finalized before first database lock. For these analyses, details of healthcare 
resource utilization for all infants will be assessed at each MA-RTI visit from birth through 
the last study visit (730 days after birth). Univariate summaries of healthcare resource 
utilization variables will be compared between the RSVpreF and placebo groups. The 
summarized variables may include the following: number and type (eg, respiratory, reactive 
airway disease [RAD]/asthma/wheezing) of medical visits (eg, outpatient, urgent care, 
emergency room, hospitalization, ICU), length of hospital stay, requirement for mechanical 
ventilation (yes/no, total number of episodes, total number of hours/days on treatment), 
requirement for IV fluids, requirement for respiratory diagnostic procedures (eg, chest 
radiograph, supplemental oxygen, pulse oximetry), requirement for prescriptions (eg, total 
number of prescriptions, selected respiratory medications [eg, bronchodilators, corticosteroid 
therapy, racemic epinephrine]), and antibiotic use (eg, total number of prescriptions, number 
of use days).
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9.5. Interim Analyses
An interim analysis may be performed to assess efficacy and safety after at least 50% of the 
planned number of cases of MA-LRTI due to RSV have occurred. Because of the relatively 
low number of cases of severe MA-LRTI due to RSV expected, the interim analysis will not 
consider that endpoint. Interim analysis results may be used for internal business decisions 
regarding future study planning, stopping for futility, or stopping for early success.
The order of cases included in the interim analysis will be determined by the adjudication 
committee as those first confirmed as meeting the protocol-defined criteria. When the target 
number of cases for the interim analysis is reached, it is possible that additional potential 
cases will be under adjudication. These additional cases will be included in the interim 
analysis only if confirmed as cases by the EAC on the same day that the last per-protocol 
case is confirmed.
The analysis of efficacy will utilize an O’Brien-Fleming alpha spending rule based on the 
fraction of cases of MA-LRTI due to RSV available. For example, to control the overall 
type 1 error for the primary endpoint at 2.5% 1-sided, an interim analysis at 50% of the target 
number of cases would use a 1-sided significance level of 0.14%. The final analysis at the 
target number of cases would use a 1-sided significance level of 2.45%. The alpha levels 
used at interim and final analyses will depend on the exact fraction of cases available at the 
interim analysis.
Testing of the primary endpoints at the interim analysis will follow the sequence of 
interval-specific tests as described in Section 9.4.1.  However, consideration will be given to 
stopping the study for efficacy only if all time intervals through 180 days indicate statistically 
significant efficacy. Secondary endpoints will not be tested at the interim analysis.
Futility will also be assessed using conditional power. Full details will be defined in the 
SAP. For example, if there are 62 cases available for the interim analysis, Table 7 indicates 
case splits for which stopping the study will be considered. The actual number of cases 
available may be slightly higher or lower than 62, and the decision rules amended 
accordingly.
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals at an 
Interim Analysis
Total Cases
RSV Vaccine 
Group Cases
Placebo Group 
Cases
VE (CI)a
Notes
62
29
33
12% (-49%, 49%)
Conditional power 
<20%,b possible 
futility declaration
62
15
47
68% (24%, 88%)
Maximum number 
of RSV cases 
permitted to 
declare VE >20%
Abbreviation: VE = vaccine efficacy.
a.
99.7% confidence level for efficacy declaration; 95% confidence level for futility.
b.
Other conditional power levels may be considered as a trigger for a futility decision.
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Before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan, and method of maintaining the study blind as per Pfizer’s standard 
operating procedures (SOPs) will be documented and approved in the DMC charter.  In 
addition, the analysis details must be documented and approved in an interim analysis SAP 
or final SAP.
9.5.1. Data Monitoring Committee
This study will use an E-DMC.  Refer to the E-DMC charter for further details.
The E-DMC will review safety data at defined intervals as specified in the charter.  The 
E-DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.
The E-DMC may review unblinded data during closed meeting sessions; however, the 
sponsor will remain blinded and will not be permitted access to the randomization 
assignments until the database is locked and unblinded.
After each meeting, the E-DMC will make recommendations that may include continuing the 
study with or without modification or pausing or stopping vaccination for safety or other 
reasons.
The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints, to regulatory authorities, as appropriate.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the maternal 
participant and answer all questions regarding the study.
Maternal participants must be informed that their participation is voluntary.  Maternal 
participants will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability 
and Accountability Act (HIPAA) requirements, where applicable, and the IRB/EC or study 
center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
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A copy of the ICD(s) must be provided to the maternal participant.
Before any study-specific activity is performed, the investigator, or a person designated by 
the investigator, will obtain written informed consent from each maternal participant.  This 
will include written informed consent for the mother and the fetus during the pregnancy, and 
the infant’s continuation in the study after delivery.  Informed consent will be obtained from
the father of the fetus/infant if mandated by local requirements.
Participants who are rescreened may be required to sign a new ICD as per IRB, local 
regulations, etc.
If during the study, the investigator determines that the maternal participant is for any reason 
no longer capable of providing informed consent, the infant’s continued participation in the 
study requires consent to be obtained from the parent(s)/legal guardian as determined by 
local regulations, legal requirements, and the IRB/EC. 
Note: For the infant participant, the term parent(s)/legal guardian denotes the “legally 
authorized representative.”
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
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10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (clinical study report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the US Basic 
Results document is posted to www.clinicaltrials.gov.
Documents Within Marketing Authorization Packages/Submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
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procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan/contracts.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
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Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the site Source Data Agreement 
Plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
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The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study 
(or study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
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10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
For maternal immunization clinical studies conducted in pregnant women, data on the EDP
including any SAEs/nonserious AEs as well as pregnancy outcomes are collected and 
analyzed in the clinical database. All SAEs are reported to Pfizer Safety using the Vaccine 
SAE Reporting Form. In case of a new pregnancy in a maternal participant before the end of 
the study, any exposure to the investigational product is reportable to Pfizer Safety within 
24 hours of investigator awareness using the Vaccine SAE Reporting Form/EDP 
supplemental form.
The term “participant” in this section refers to (1) the maternal participant and her fetus; and 
after delivery (2) the maternal participant and (3) the infant participant.
10.2.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (eg, cesarean section, endoscopy, appendectomy): the 
condition that leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs)
An NDCMC is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
10.2.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
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serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a Pfizer 
product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited 
cases by pharmacovigilance personnel.  Such cases are also considered for reporting as 
product defects, if appropriate.
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10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording safety events on the CRF and 
for reporting safety events on the Vaccine SAE Reporting Form to Pfizer Safety.  These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and 
(3) occupational exposure. 
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study via 
occupational exposure
Occupational exposure is not 
recorded.
Occupational exposure 
(regardless of whether 
associated with an AE)
Note:  Include all 
AEs/SAEs associated with 
occupational exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.
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
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING
to describe the maximum intensity of the AE. For purposes of 
consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent 
intervention indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.
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
The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused the 
event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible.  This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any anonymized
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
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10.2.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
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10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
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
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with International 
Organization for Standardization (ISO) 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.4.1. Definition of AE and ADE
AE and ADE Definition 

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational medical device.  
This definition includes events related to the investigational medical device or 
comparator for study participants, users, and other persons.  This definition also 
includes events considered related to procedures for study participants only.

An ADE is defined as an AE related to the use of an investigational medical device.  
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
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10.4.2. Definition of Serious Adverse Event, Serious Adverse Device Effect, and 
Unanticipated Serious Adverse Device Effect
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is an AE that:
a. Led to death.
b. Led to serious deterioration in the health of the participant, that either resulted 
in:

A life-threatening illness or injury.  The term “life-threatening” in the definition of 
serious refers to an event in which the participant was at risk of death at the time of 
the event. It does not refer to an event that hypothetically might have caused death, 
if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
SADE Definition

A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE.
Unanticipated Serious Adverse Device Effect (USADE) Definition

A USADE is a serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis management 
file.
10.4.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance.  Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
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10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator 
to review all documentation (eg, hospital progress notes, laboratory reports, and 
diagnostic reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information in 
the participant’s medical records, in accordance with the investigator’s normal clinical 
practice and on the appropriate form of the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of following the reporting process described in the IP 
manual.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
“severe” should not be confused with an SAE. “Severe” is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as “severe.”
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
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as “severe.”
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency and has 
provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE/SAE/Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE/SAE/ device deficiency 
as fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.
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
If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.4.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred 
method to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.4.6. Reporting of SADEs
SADE Reporting to Pfizer Safety 
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.
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10.5. Appendix 5: Background Factors
1. Information on the following will be collected at Visit 1, Visit 4 (12-Month), and 
Visit 6 (24-Month) for all infant participants:

Educational level of parent(s) or legal guardian(s).

Exposure to smoke (including tobacco smoke).

Number of persons in the household ≥18 years of age.

Number of children <18 years of age in the household and if they attend school/ 
daycare.
o
Number of children in the household under 5 years of age (under 60 months).
o
Number of children in the household ≥5 years of age (≥60 months).
2. Information on the following will be collected at each postbirth visit:

Childcare/daycare (for infant participants).

Breastfeeding information (including whether or not breastfeeding is exclusive).
3. Information on the following will be collected at each RTI study visit:

Number of missed days of work for parent(s) or legal guardian(s) due to the infant 
participant’s illness.
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10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria Checklist 
for MA-RTI Visit – Infant Participants
When an infant MA-RTI medical visit criterion is met or confirmed, the site will obtain 
records from the medical visit and capture the healthcare information as detailed below in the 
eCRF. This information is based on respiratory-related assessments including examination 
findings, clinical findings, and any pathogen-related assessments/findings. 
Medical Visit - Visit Details and Assessment Requirements
Note: This should not be linked to a study visit but may overlap with the RTI study visit. 
The following fields and clinical assessment details should be obtained from relevant 
records for the medically attended event prior to each RTI study visit to support the 
assessment of the RTI event.

Reason for visit including date/time, eg,
o
Nasal discharge for 24 hours or more.
o
Difficulty breathing, labored breathing, or rapid breathing for any duration.
o
Cough.
o
Inability to feed for any duration due to respiratory symptoms.
o
Apnea.
o
Any other respiratory symptom of concern.

Location of medical visit (inpatient clinic, outpatient clinic, emergency department, 
urgent care, hospitalization, home visit, other). Note: study visits should NOT be 
recorded here.
o
If hospital visit, was this triggered by an RTI (include details pertaining to duration
as well as admission and discharge information and records)?

Clinical findings pertaining to respiratory symptoms and/or RTI, as detailed below but 
not limited to:
o
Presence or absence of pertinent examination findings, eg, apnea (documented as per 
chart), wheezing, fever, cough, nasal congestion, intercostal retractions, lower chest 
wall indrawing, grunting, crackles, decreased breath sounds, other abnormal breath 
sounds, dry mucous membranes, skin tenting, sunken fontanelle, difficulty feeding, 
failure to respond/unconsciousness, etc. 
o
Respiratory rate from highest/worst value of visit.
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o
Oxygen saturation (SpO2) from lowest/worst value of visit.
o
Oxygen supplementation (assisted ventilation, including type of respiratory assistance 
[respirator, “state-of-the-art” occlusive nasal prongs, face tent, etc]).

Days of supplementary oxygen.

Use of nasal cannula.

Use of high-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive).
o
Heart rate from worst value of visit when performed consistently.
o
Body weight from the date of the MA-RTI event.
o
Temperature from worst value of visit when performed consistently.
o
Additional clinical or respiratory related assessments including chest x-ray.

Local test results for RSV as part of routine clinical care:
o
Testing platform used (clinical list of all platforms and validated by research).
o
Result (list: positive, negative, indeterminate, other).

Results for any local non-RSV respiratory pathogen testing conducted as part of routine 
clinical care:
o
Result (list: detected, not detected, indeterminate)

Record the provider diagnosis, including any causative pathogen (if applicable), eg, RSV 
bronchiolitis, asthma, influenza, etc.

Obtain details of all prescribed medications including IV fluid usage.

Obtain details of all AEs/SAEs in line with study requirements. Note: MA-RTIs are not 
AEs/SAEs, unless related to the investigational product or resulting in death.
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10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
10.7.1. Informed Consent for the Maternal Participants 18 to <20 Years Old
Informed consent for maternal participants 18 to <20 years old and their infant participants 
will be obtained based on current Japanese civil code article 753 until 01 April 2022.

Married maternal participants 18 to <20 years of age are deemed to have reached 
“majority” and each maternal participant will sign the ICD for her and her infant’s study 
participation.

Unmarried maternal participants 18 to <20 years of age are deemed “minors.”

When the maternal participant is a minor under local law, the investigator, or a person 
designated by the investigator, will obtain written informed consent from the maternal 
participant’s legally acceptable representative, parent(s), or legal guardian as well as 
the maternal participant’s assent (affirmative agreement) for her and her child’s study 
participation before any study-specific activity is performed. The investigator will 
retain the original of each signed consent and assent document.

The assent form for a minor must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements, including applicable privacy 
laws.

The assent form for a minor used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB before use, and available for 
inspection.

The investigator must ensure that the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian is fully informed about the nature and 
objectives of the study and possible risks associated with participation.

The source documents must record that the maternal participant was a minor at 
the time of signing the ICD, how the investigator determined that the person 
signing the consent was the maternal participant’s legally acceptable 
representative, the consent signer’s relationship to the maternal participant 
(eg, parent), and that the maternal participant’s assent was obtained.

When the minor maternal participants reach the age of majority during the study, as 
recognized under local law, they must reconsent as adults to remain in the study.

Beginning on 01 April 2022, when the amended civil law in which individuals 18 years 
of age and older are deemed to have reached majority is implemented, the investigator, or 
a person designated by the investigator, will obtain written informed consent from the 
maternal participant.
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10.7.2. Temperature Measurement and Definition of Fever

Axillary temperature will be measured at Visit 1 and as required at an unscheduled visit, 
and will be measured by the maternal participants for 7 days following vaccination.

For the maternal participants enrolled in Japan, an axillary temperature of ≥37.5°C
(99.5°F) meets the definition of a current febrile illness in the criteria for temporarily 
delaying vaccine administration described in Section 5.2.3.

For the purpose of recording the temperature in the e-diary, fever is defined as an axillary
temperature of ≥38.0°C (100.4°F) for maternal participants enrolled in Japan.
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants
As Study C3671008 is a first-in-Japanese study and in accordance with a recommendation 
from the Pharmaceuticals and Medical Devices Agency (PMDA), the study will utilize a 
sentinel cohort for the maternal participants enrolled in Japan with progression to study 
enrollment at all study sites after a safety review (data from each maternal participant 
through 14 days after vaccination).  In addition to the study procedures and requirements 
specified in the protocol for Study C3671008, the following procedures will be required for 
the maternal participants enrolled in the sentinel cohort in Japan.
10.7.3.1. Enrollment of Maternal Participants in the Sentinel Cohort
In the sentinel cohort, approximately 8 maternal participants will be enrolled.  No more than 
4 maternal participants per day can be randomized.  Vaccination of the remaining maternal 
participants in the sentinel cohort will commence no sooner than 48 hours after the fourth 
participant received her vaccination.  
10.7.3.2. Conclusion of the Sentinel Cohort
After enrollment in the sentinel cohort is completed, the Pfizer internal review committee 
(IRC) will review at least 14 days of postvaccination safety data from all maternal 
participants enrolled in the sentinel cohort, including all local reactions, systemic events, and 
AEs.  An acceptable review will trigger an expansion of study enrollment to all study sites in 
Japan. Refer to the IRC charter for further details.
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or Telephone; 14 to 16 Days 
After Vaccination)
All maternal and infant participants enrolled in this study will follow the protocol for 
Study C3671008.  In addition, the maternal participants enrolled in the sentinel cohort in 
Japan will have a Day 15 follow-up visit conducted either at the study site or via telephone.  
This visit should be conducted 14 to 16 days after vaccination. 

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.
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
Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given since the last visit.

Review the participant’s e-diary data.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6.

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit.
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10.7.3.4. Schedule of Activities for Maternal Participants Enrolled in the Sentinel Cohort in Japan
The following table provides an overview of the protocol visits and procedures for the maternal participants enrolled in the sentinel 
cohort in Japan.  Refer to Section 1.2.3.1 for the Schedule of Activities for the Maternal Participants: RTI Surveillance for Medically 
Attended Respiratory Tract Illness Visits (Vaccination Until the End-of-Study Visit).
Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to 
Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Informed consent for maternal participant and her 
infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current/former alcohol, tobacco, marijuana, or 
any illicit drug usage
X
Record vital signs
X
Targeted physical and obstetric examination performed 
on the same day or within 7 days before the 
vaccination visit
X
Record details of any antenatal and/or postnatal steroid 
treatment, monoclonal antibodies, blood products, or 
Rho(D) immune globulin
X
X
X
X
X
Record details of the maternal participant’s GBS status 
and if any medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
X
Review eligibility criteria
X
X
X
X
Review temporary delay criteria
X
Prevaccination blood draw for serologic assessment
(~15 mL) on the same day or within 7 days before the 
vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and 
measuring devicef
X
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Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to 
Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity Unit
Clinic, Home, or 
Telephone
Obtain and record baseline assessment of prespecified 
systemic events on the day of and prior to 
vaccination in the e-diary
X
Administer investigational product
X
Postvaccination observation (at least 30 minutes) and 
assessment of immediate AEs
X
Delivery blood draw for serologic assessment 
(~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X
X
Record AEs, as appropriateh
X----------------------------------------------------X
Record SAEs, as appropriateh
X
X
X
X
X
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of the schedule 
of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; ICD = informed 
consent document; MA-RTI = medically attended respiratory tract illness.
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Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
28 Days Prior to 
Vaccination to 
Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity Unit
Clinic, Home, or 
Telephone
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.
Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.
AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.
Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and/or the study staff/field worker (as per local practice) will record (in an e-diary) a 
baseline assessment of prespecified systemic events on the day of and prior to vaccination and reactogenicity events from Day 1 to Day 7 following 
vaccination (where Day 1 is the day of vaccination).  Remind maternal participants that the study staff/field worker may contact them to obtain additional 
information on events entered into the e-diary.  Ask maternal participants to contact the investigator or site staff immediately if they are prompted by the 
e-diary from Day 1 to Day 7 following vaccination, to determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the 
maternal participant may be referred to the appropriate healthcare facility at the discretion of the study staff/field worker if there are any concerns.
g.
Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs through 28 days after vaccination.  From the signing of 
the ICD until the maternal participant completes the study, all SAEs will be collected.  Please see Section 8.3.1 for reporting requirements and timelines.
i.
A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product or to 
have resulted in death.
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10.7.4. Exclusion Criterion 12 Clarification
For exclusion criterion 12, “Current alcohol abuse or illicit drug use. Note: Marijuana use is 
not considered an illicit drug for study eligibility” in Section 5.2.1, any current use of an 
illicit drug including marijuana will not be permitted for maternal participants enrolling from 
study sites in Japan.
10.7.5. Definitions of SAE, SAE Caused by Medical Device, and Unanticipated SAE
Caused by Medical Device
Definition of SAE caused by medical device:
An SAE caused by medical device is defined as an AE caused by a medical device which led 
to an outcome characteristic to SAEs, or a device-related incident whose recurrence might 
lead to death or serious deterioration in health.
NOTE: See the Medical Device Adverse Events, Adverse Device Effects, Serious Adverse 
Events, and Device Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting section (Appendix 4). Deficiencies fulfilling the definition of an 
AE/SAE will also follow the processes outlined in Section 8.3.3 and Appendix 2 of the 
protocol.
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix – Applicable 
to the Gambia and South Africa Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Participants who have not had ultrasound assessments to determine eligibility during 
routine care should be consented, and have an ultrasound within 90 days prior to
vaccination in order to comply with inclusion criteria #1 in Section 5.1.1.
Safety endpoints:
The time period and frequency for collecting AE and SAE information by the investigator 
and site staff should follow Appendix 2, with the exception of the additional screening 
window for sites conducting ultrasounds procedures from -90 to -28 days. At these sites, the 
safety reporting periods should be as follows:

AEs occurring up to 48 hours after ultrasound assessment that the investigator 
deems are related to the study procedure must be reported in the CRF.

The active collection period for SAEs begins once informed consent has been 
provided until the maternal participant completes the study.

The active collection period for nonserious AEs begins 28 days prior to 
vaccination and continues through a minimum of 28 calendar days after
vaccination as described in Section 8.3.1 and Section 10.2.
MA-RTI endpoints:
Maternal MA-RTIs are collected from the time of vaccination to the end of the study period 
as described in Section 8.1.2.
Note: For maternal participants who are screen failures, the active collection period ends 
when screen failure status is determined. 
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10.9. Appendix 9: Country-Specific Age Requirements Appendix - Applicable to South 
Korea and Taiwan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Section 5.1.1: Inclusion criterion 1 states that healthy women ≥18 and ≤49 years of age who 
are between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an 
uncomplicated, singleton pregnancy, who are at no known increased risk for complications 
are eligible for the study.
Please find below country-specific minimum age requirements for study entry into the 
protocol:

In South Korea, the minimum age requirement of maternal participants who can be 
enrolled into the study is ≥19 years of age.

In Taiwan, the minimum age requirement of maternal participants who can be 
enrolled into the study is ≥20 years of age.
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10.10. Appendix 10: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ADE
adverse device effect
AESI
adverse event of special interest
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
Apgar
appearance, pulse, grimace, activity, and respiration
AST
aspartate aminotransferase
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
Clinical Laboratory Improvement Amendments
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EAC
endpoint adjudication committee
EACC
endpoint adjudication committee charter
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine 
GA
gestational age
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Abbreviation
Term
GBS
group B streptococcal
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBIG
hepatitis B immune globulin
HBV
hepatitis B virus
HCP
healthcare provider
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IAP
intrapartum antibiotic prophylaxis
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
Ig
immunoglobulin
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ISF
investigator site file
ISO
International Organization for Standardization
IUI
intrauterine insemination
IV
intravenous
IWR
interactive Web-based response
LFT
liver function test
LMIC
lower- and middle-income country
LMP
last menstrual period
LRTI
lower respiratory tract illness
MA-LRTI
medically attended lower respiratory tract illness
MA-RTI
medically attended respiratory tract illness
MCAR
missing completely at random
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NAAT
nucleic acid amplification technology
NDCMC
newly diagnosed chronic medical condition
PCD
primary completion date
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Abbreviation
Term
PCR
polymerase chain reaction
PFS
prefilled syringe
PMDA
Pharmaceuticals and Medical Devices Agency
PT
prothrombin time
RAD
reactive airway disease
RCDC
reverse cumulative distribution curve
RSV
respiratory syncytial virus
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RTI
respiratory tract illness
RT-PCR
reverse transcription–polymerase chain reaction
SAE
serious adverse event
SADE
serious adverse device effect
SAP
statistical analysis plan
SMS
short message service
SoA
schedule of activities
SOP
standard operating procedure 
SpO2
oxygen saturation
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Tdap
tetanus, diphtheria, and acellular pertussis vaccine
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VE
vaccine efficacy
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11. REFERENCES
1
Meissner HC. Respiratory syncytial virus. In: Long SS, Prober CG, Fischer M, eds. 
Principles and practice of pediatric infectious diseases. 5th ed. Philadelphia, PA: 
Elsevier; 2018:1162-5. 
2
Hall CB, Weinberg GA, Blumkin AK, et al. Respiratory syncytial virus–associated 
hospitalizations among children less than 24 months of age. Pediatrics 
2013;132(2):e341-8.
3
Shi T, McAllister DA, O’Brien KL, et al. Global, regional, and national disease burden 
estimates of acute lower respiratory infections due to respiratory syncytial virus in young 
children in 2015: a systematic review and modelling study. Lancet
2017;390(10098):946-58.
4
Scheltema NM, Gentile A, Lucion F, et al. Global respiratory syncytial virus-associated 
mortality in young children (RSV GOLD): a retrospective case series. Lancet Glob
Health 2017;5(10):e984-91.
5
Parikh RC, McLaurin KK, Margulis AV, et al. Chronologic age at hospitalization for 
respiratory syncytial virus among preterm and term infants in the United States. Infect
Dis Ther 2017;6(4):477-86.
6
American Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis 
Guidelines Committee. Policy statement—updated guidance for palivizumab 
prophylaxis among infants and young children at increased risk of hospitalization for 
respiratory syncytial virus infection. Pediatrics 2014;134(2):415-20.
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Blanken MO, Rovers MM, Molenaar JM, et al. Respiratory syncytial virus and recurrent 
wheeze in healthy preterm infants. N Engl J Med 2013;368(19):1791-9.
8
Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk 
of wheeze and allergy by age 13 years. Lancet 1999;354(9178):541-5.
9
Weber MW, Mulholland EK, Greenwood BM. Respiratory syncytial virus infection in 
tropical and developing countries. Trop Med Int Health 1998;3(4):268-80.
10
Glezen WP, Taber LH, Frank AL, et al. Risk of primary infection and reinfection with 
respiratory syncytial virus. Am J Dis Child 1986;140(6):543-6.
11
American Academy of Pediatrics. Respiratory syncytial virus. In: Kimberlin DW, Brady 
MT, Jackson MA, Long SS, eds. Red book: 2018 report of the Committee on Infectious 
Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:682-92. 
12
Prescott WA Jr, Doloresco F, Brown J, et al. Cost effectiveness of respiratory syncytial 
virus prophylaxis: a critical and systematic review. Pharmacoeconomics
2010;28(4):279-93.
13
Synagis [prescribing information]. Gaithersburg, MD: MedImmune LLC; 2017.
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14
Munoz FM, Ralston SL, Meissner HC. RSV recommendations unchanged after review 
of new data. AAP News 19 Oct 2017. Available from: 
http://www.aappublications.org/news/2017/10/19/RSV101917. Accessed 15 Nov 2018. 
15
The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus 
monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection 
in high-risk infants. Pediatrics 1998;102(3):531-7.
16
Baker CJ, Carey VJ, Rench MA, et al. Maternal antibody at delivery protects neonates 
from early onset group B streptococcal disease. J Infect Dis 2014;209(5):781-8.
17
Dangor Z, Kwatra G, Izu A, et al. Correlates of protection of serotype-specific capsular 
antibody and invasive group B Streptococcus disease in South African infants. Vaccine
2015;33(48):6793-9.
18
Skoff TH, Blain AE, Watt J, et al. Impact of the US maternal tetanus, diphtheria, and 
acellular pertussis vaccination program on preventing pertussis in infants <2 months of 
age: A case-control evaluation. Clin Infect Dis 2017;65(12):1977-83.
19
Baxter R, Bartlett J, Fireman B, et al. Effectiveness of vaccination during pregnancy to 
prevent infant pertussis. Pediatrics 2017;139(5):e20164091.
20
Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and 
protection of their infants. N Engl J Med 2014;371(10):918-31. 
21
Benowitz I, Esposito DB, Gracey KD, et al. Influenza vaccine given to pregnant women 
reduces hospitalization due to influenza in their infants. Clin Infect Dis 
2010;51(12):1355-61.
22
Forbes ML, Kumar VR, Yogev R, et al. Serum palivizumab level is associated with 
decreased severity of respiratory syncytial virus disease in high-risk infants. Hum 
Vaccin Immunother 2014;10(10):2789-94.
23
Schmoele-Thoma B, Falsey AR, Walsh EE, et al. Phase 1/2, first-in-human study of the 
safety, tolerability, and immunogenicity of an RSV prefusion F-based subunit vaccine 
candidate [poster 2755]. Poster presented at IDWeek; 02-06 Oct 2019; Washington, DC.
24
McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer 
bound to a prefusion-specific neutralizing antibody. Science 2013;340(6136):1113-7.
25
Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants 
despite prior administration of antigenic inactivated vaccine. Am J Epidemiol
1969;89(4):422-34. 
26
Graham BS. Biological challenges and technological opportunities for respiratory 
syncytial virus vaccine development. Immunol Rev 2011;239(1):149-66.
27
Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial 
virus purified fusion protein-2 vaccine in pregnant women. Vaccine 2003;21(24):3465-7.
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28
Madhi SA, Polack FP, Piedra PA, et al. Respiratory syncytial virus vaccination during 
pregnancy and effects in infants. N Engl J Med 2020;383:426-39. 
29
Regen AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization 
during pregnancy in 4 high-income countries, 2010–2016.  Clin Infect Dis 
2018;67(12):1915-8. Available from: https://doi.org/10.1093/cid/ciy439. Accessed: 
25 Nov 2019.
30
Pettker CM, Goldberg JD, El-Sayed YY, et al. Committee opinion number 700: methods 
for estimating the due date. Obstet Gynecol 2017;129(5):e150-54.
31
European Commission. Ethical considerations for clinical trials on medicinal products
conducted with minors. 18 Sep 2017. Available from:
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/2017_09_18_ethical_consid_ct_with_minors.pdf. Accessed 21 Feb 2019.
32
Centers for Disease Control and Prevention. Metropolitan atlanta congenital defects 
program. Available from: https://www.cdc.gov/ncbddd/birthdefects/macdp.html. 
Accessed: 09 Jun 2020.
33
Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: case definition & guidelines for 
data collection, analysis, and presentation of immunisation safety data. Vaccine 
2016;34(49):6047-56.
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Document Approval Record
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PPD
PPD

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671008
Protocol Amendment 2, Regional-Specific, 26 June 2020
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLINDED,
PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND 
SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F 
SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING 
PREGNANCY
Investigational Product Number:
PF-06928316 
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine 
United States (US) Investigational New 
Drug (IND) Number:
017931
European Clinical Trials Database 
(EudraCT) Number:
2019-002943-85
Protocol Number:
C3671008
Phase:
3
Short Title: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants 
Born to Women Vaccinated During Pregnancy.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Page 2
Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original protocol
05 December
2019
Not applicable (N/A)
Protocol 
Amendment 1
24 March 2020
PROTOCOL SUMMARY: Clarification text was 
added in various sections of the main body of the 
protocol to match the revisions made to the protocol 
summary.
Throughout: The protocol now contains final 
wording regarding the double-blinded, placebo-
controlled study design and the final dose and 
formulation of the respiratory syncytial virus 
stabilized prefusion F subunit vaccine (RSVpreF). 
This is as a result of the analysis of the safety, 
tolerability, and immunogenicity data from the 
C3671003 maternal Phase 2b trial.
Section 1.2.1 Study Design – Maternal Participants: 
The final dose and formulation of RSVpreF were 
inserted, including the lyophile match for the 
placebo.
Section 1.2.2 Study Design – Infant Participants: 
The text box pertaining to the vaccine group arms 
was deleted. The maternal-infant dyads will be 
randomly assigned in this study. Rationale: Infant 
participants will not be administered the 
investigational product. Therefore, the current 
placement is potentially confusing to readers.
Section 1.2.3 Schedule of Activities for Maternal 
Participants, Section 5.2.3, and Section 8.10.1: 
Clarification text was added as follows:
o
The immunogenicity blood collection and 
physical examination window requirements 
before vaccination were aligned to provide 
greater logistical convenience for the 
investigational sites with respect to enrolling 
participants into the study.
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Document History
Document
Version Date
Summary of Changes and Rationale
o
The wording for the study objectives pertaining 
to the request for intrapartum antibiotic 
prophylaxis (IAP) details for maternal 
participants with a group B streptococcal (GBS) 
status was revised to be consistent with the 
study procedural objectives, which are to collect 
GBS status and to ascertain whether any 
medication was given for IAP. This resulted in 
the deletion of the text in Section 6.5.3, as this 
information is captured in Section 8.10.3.
o
A reference to the immunogenicity blood draws 
for maternal participants was added to clarify 
the adverse event (AE) reporting requirements 
for events that might occur as a result of study-
related procedures.
Section 1.2.3.1 Schedule of Activities for Maternal 
Participants – Respiratory Tract Illness (RTI) 
Surveillance for Medically Attended Respiratory 
Tract Illness (MA-RTI) Visits: 
o
Details to be collected during an MA-RTI were 
revised.
o
Clarification was added regarding the safety 
reporting requirements for MA-RTI events that 
might occur during the study. 
Section 1.2.4 Schedule of Activities for Infant 
Participants: 
o
Visit flexibility was increased to prioritize 
participant safety and adherence to local 
guidance in the event of a coronavirus disease 
2019 (COVID-19) outbreak or other outbreaks. 
o
The physical examination and vital sign 
assessment windows for the study were aligned 
to provide greater logistical convenience for the 
investigational sites with respect to compliance 
to study protocol requirements.  
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Document History
Document
Version Date
Summary of Changes and Rationale
o
The protocol safety reporting criteria and period 
for adverse events (AEs), serious adverse events 
(SAEs), and newly diagnosed chronic medical 
conditions (NDCMCs) were streamlined.
Section 1.2.4.1 Schedule of Activities for Infant 
Participants: RTI Study Visits During the Study: 
The table was revised, including splitting the 
schedules of activities for unscheduled RTI visits 
for all infant participants into RTI surveillance from 
birth to 6 months and RTI surveillance from 6 
months to the end of the study. The procedures were 
streamlined for these RTI study visits to improve 
clarity and consistency.
Table 1: Clarification has been added as to when a 
study visit is triggered for reported MA-RTI 
endpoint events on the study. Day 1 is the day of the 
MA-RTI visit as detailed in Section 8.11.7.
In addition, clarification has been added as to what 
constitutes the site source for confirmed study 
endpoint criteria, in order to provide the sites 
guidance on what documentation will eventually be 
submitted to the endpoint adjudication committee 
(EAC) for evaluation.
Section 3.1: The exploratory endpoints were revised 
to correspond with the planned statistical analyses 
of RTI events in the pediatric population. This does 
not represent a change to the study design but 
instead better reflects the total statistical analysis 
plan. 
Section 3.1, Section 3.2, and throughout: To 
improve clarity and ensure consistency, the use of 
“RSV-neutralizing antibody titers” has been 
changed to RSV serum neutralizing titers.” This is 
the sponsor’s preference based on what the 
neutralizing activity assay is based upon, and in this 
case, it is whole serum and not just the purified 
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Summary of Changes and Rationale
antibodies during these immunogenicity 
assessments.
Section 3.3, Section 8.1.1.2, Section 8.1.3, and 
Section 10.2: For further clarification, the protocol’s 
safety and endpoint reporting requirements were 
amended to ensure consistency with Pfizer’s 
updated safety reporting requirements for endpoint-
defined studies.
Section 4.3: The text “availability of these data are 
expected in 2020” was removed as this statement 
does not accurately reflect the current decision-
making process for the dose and formulation 
selection activities for this study. 
Section 5.2.1: Clarification text was added to the 
exclusion criterion for body mass index (BMI) and 
congenital anomalies based on study requirements.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: The 
tetanus, diphtheria, and acellular pertussis vaccine 
(Tdap) administration requirements text was 
modified to describe the timing of vaccinations 
based on data from the C3671004 study, once 
available. This change will better reflect clinical 
practice and will facilitate recruitment of suitable 
maternal participants for the study.
Section 6.1.1, Section 6.1.3, Section 8.4, and
Section 8.10.1: Clarification text was added to 
address investigational product reconstitution 
volume and administration requirements. This 
change is to ensure consistency with the 
investigational product administration 
documentation for the study.  
Section 7.2: Clarification text was added to address 
the notification process for biological sample 
management in the event of study participant 
withdrawal from the study.
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Document
Version Date
Summary of Changes and Rationale
Section 7.3 and Appendix 1 Informed Consent 
Process: Clarification text was added to address 
study retention and data collection requirements for 
the study. In addition, further clarification has been 
added to emphasize the informed consent process 
during circumstances where the maternal participant 
is no longer able to provide consent but the infant 
participant’s continued participation in the study 
could be retained by the parent(s)/legal guardian as 
per local regulatory, local laws, and local 
governance approval.
Section 8.1.1.1: Clarification text was added to 
provide guidance regarding the midturbinate swab 
processing requirements and the definition of 
acceptable certified/accredited laboratory bodies for 
this process in the study.
Section 8.2.1.1 and Section 8.10.1: The reporting 
requirements for Grade 4 local reactions in the study 
were clarified; the assessment and reporting are 
carried out by the investigators (or appropriately 
qualified designees).
Section 8.3.1.1, Section 8.3.1.2, Section 8.3.5.1,
Section 8.3.5.2, Section 8.10, and Section 8.11: The 
reporting requirements were clarified for this 
vulnerable patient population with regard to AEs
and SAEs likely to occur in the study in women 
with gestational age (GA) eligibility criterion 
between 24 0/7 and 36 0/7 weeks.
Section 8.3.6: Text was added to address and 
standardize reporting procedures for adverse events 
of special interest (AESIs) for this patient 
population.
Section 8.3.7 and Appendix 4: Several Pfizer text 
revisions were incorporated regarding device 
deficiencies and the safety reporting requirements 
for this study.
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Version Date
Summary of Changes and Rationale
Section 8.10: The immunogenicity blood collection 
and physical examination window requirements 
before vaccination were aligned to provide greater 
logistical convenience for the investigational sites 
with respect to enrolling participants into the study. 
Section 8.10.1: The prepregnancy BMI text 
revisions in Section 5.2.1 were aligned with the 
study assessment requirements for maternal 
participants at screening.
Section 8.10.2, Section 8.10.3, Section 8.10.4, and 
Section 8.10.6: Clarification text was added to the 
MA-RTI reporting requirements for maternal 
participants in the study to provide guidance and 
ensure the investigational sites provide accurate 
information pertaining to these self-reported events.
Section 8.11.1 to Section 8.11.6: Clarification text 
was added (where applicable) to address the 
following study assessments:
o
“Birth weight must be the first birth weight and 
cannot be based on the standard-of-care 
examination” was removed as this statement is 
confusing to the investigational sites. Birth 
weight assessments have now been realigned 
with standard-of-care assessments at the study 
visit to aid compliance with study assessments 
and requirements.
o
Clarification text was added regarding the 
reporting of standard-of-care measurements for 
vital sign assessments. 
o
In addition, the physical examination and vital 
sign assessment windows for the study were 
aligned to provide greater logistical convenience
for the investigational sites to comply with study 
protocol requirements.  
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Page 8
Document History
Document
Version Date
Summary of Changes and Rationale
o
For further clarification, the RTI study visit 
assessment requirements were amended to 
emphasize the difference between the MA-RTI 
visit criteria and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements. 
Section 8.11.7.1: For further clarification, the RTI 
study visit assessment requirements have been 
amended to emphasize the following:
o
The RTI study visit window, including nasal 
swab collection from the MA-RTI notification 
for the infant participant.
o
Duplicate text was removed pertaining to the 
MA-RTI definition and the signs and symptoms 
of interest pertinent to an RTI study visit.
o
Guidance regarding the difference between the 
MA-RTI visit and the subsequent study visit 
after the event has been reported. This is to 
improve clarity and consistency with the RTI 
study visit requirements.
Section 8.11.8: Clarification text was added to 
address the RTI study visit window, including nasal 
swab collection from the MA-RTI notification for 
the infant participant.
o
For further clarification, the RTI study visit 
assessment requirements have been amended to 
emphasize the difference between the MA-RTI 
visit and the subsequent study visit after the 
event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements and provide guidance to the 
investigational sites.
Section 9.1.2.1, Section 9.1.2.2, Section 9.4.1, 
Section 9.2, and Section 9.5: Text was added to 
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Document History
Document
Version Date
Summary of Changes and Rationale
clarify the statistical analysis procedures in line with 
the current revisions.
Appendix 2: Clarification text was added to support 
the safety and pregnancy outcome reporting 
requirements for participants who may experience
exposure during pregnancy while in the study.
Appendix 5: Further clarification was added to the 
background factors of interest during the infant’s 
participation in the study. 
Appendix 6: Clarification text was added to the 
examination and treatment criteria checklist for 
reported MA-RTI visits.  This is to ensure there is 
some consistency to the source records provided for 
these events in relation to the protocol requirements.
Throughout: Several changes were made to 
incorporate the replacement of the Clinical Trial 
Serious Adverse Event Report Form (CT SAE 
Report Form) to Vaccine SAE Reporting Form, as 
part of the new vaccine SAE reporting requirements 
for Pfizer. 
Throughout: Minor editorial revisions were 
incorporated as appropriate. 
Protocol 
Amendment 2
26 June 2020
Section 5.1.1: Administrative update was 
incorporated to address the recently added 
Appendices 7 and 8.
Appendix 7: A country-specific appendix was added 
for Japan to address consent/assent issues for 
minors, temperature measurement, definition of 
fever, and enrollment of maternal participants in the 
sentinel cohort for safety monitoring.
Appendix 8: A country-specific appendix was added 
for the Gambia and South Africa to address an 
extension to the screening period for maternal 
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Document
Version Date
Summary of Changes and Rationale
participants with regard to GA requirements and 
consent process.
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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Page 11
TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................17
1. PROTOCOL SUMMARY...................................................................................................19
1.1. Synopsis ..................................................................................................................19
1.2. Schematic for Study Participants ............................................................................26
1.2.1. Study Design – Maternal Participants ........................................................26
1.2.2. Study Design – Infant Participants .............................................................27
1.2.3. Schedule of Activities for Maternal Participants........................................28
1.2.3.1. Schedule of Activities for Maternal Participants: RTI 
Surveillance for Medically Attended Respiratory Tract Illness 
Visits (Vaccination Until the End-of-Study Visit) ............................31
1.2.4. Schedule of Activities for Infant Participants.............................................32
1.2.4.1. Schedule of Activities for Infant Participants: Respiratory 
Tract Illness Study Visits During the Study......................................34
2. INTRODUCTION ...............................................................................................................36
2.1. Study Rationale .......................................................................................................36
2.2. Background .............................................................................................................37
2.3. Benefit/Risk Assessment.........................................................................................38
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................39
3.1. Infant Participants ...................................................................................................39
3.2. Maternal Participants...............................................................................................43
3.3. Protocol-Defined Efficacy Endpoints .....................................................................44
4. STUDY DESIGN.................................................................................................................45
4.1. Overall Design.........................................................................................................45
4.1.1. Approximate Duration of Participation for Each Participant .....................46
4.1.2. Approximate Number of Participants.........................................................46
4.2. Scientific Rationale for Study Design.....................................................................47
4.3. Justification for Dose ..............................................................................................47
4.4. End of Study Definition ..........................................................................................48
5. STUDY POPULATION......................................................................................................48
5.1. Inclusion Criteria.....................................................................................................48
5.1.1. Inclusion Criteria – Maternal Participants..................................................48
5.1.2. Inclusion Criteria – Infant Participants.......................................................51
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5.2. Exclusion Criteria....................................................................................................51
5.2.1. Exclusion Criteria – Maternal Participants.................................................51
5.2.2. Exclusion Criteria – Infant Participants......................................................53
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants ................53
5.3. Lifestyle Considerations..........................................................................................54
5.4. Screen Failures ........................................................................................................54
6. STUDY INTERVENTION..................................................................................................54
6.1. Study Intervention(s) Administered........................................................................54
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........54
6.1.2. Placebo........................................................................................................55
6.1.3. Administration............................................................................................55
6.1.4. Medical Devices .........................................................................................55
6.2. Preparation/Handling/Storage/Accountability ........................................................56
6.2.1. Preparation and Dispensing........................................................................57
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................57
6.3.1. Blinding of Study Site Personnel................................................................57
6.3.2. Blinding of the Sponsor..............................................................................57
6.3.3. Allocation to Investigational Product .........................................................57
6.3.4. Breaking the Blind......................................................................................58
6.4. Study Intervention Compliance...............................................................................58
6.5. Concomitant Therapy..............................................................................................58
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................58
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................59
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................59
6.5.4. Permitted Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................60
6.5.5. Recording Nonstudy Vaccinations and Concomitant Medications –
Infant Participants............................................................................................60
6.6. Dose Modification...................................................................................................60
6.7. Intervention After the End of the Study..................................................................60
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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................60
7.1. Discontinuation of Study Intervention ....................................................................60
7.2. Participant Discontinuation/Withdrawal From the Study.......................................60
7.3. Withdrawal of Consent............................................................................................61
7.4. Lost to Follow-up....................................................................................................61
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................62
8.1. Efficacy Assessments..............................................................................................63
8.1.1. Efficacy Assessments – Infant Participants................................................63
8.1.1.1. Midturbinate Nasal Swab Collection and Testing 
Requirements for Endpoint Confirmation – Infant Participants........63
8.1.1.2. Events for Adjudication and Submission Guidance –
Infant Participants..............................................................................64
8.1.2. Exploratory Efficacy Assessments – Maternal Participants.......................65
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal 
and Infant Participants .....................................................................................65
8.1.4. Immunogenicity Assessments ....................................................................66
8.1.4.1. Total Volume of Blood Collected – Maternal Participants.......66
8.1.4.2. Total Volume of Blood Collected – Infant Participants............66
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant 
Participants ........................................................................................66
8.1.4.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development – Maternal and Infant 
Participants ........................................................................................67
8.1.4.5. Respiratory Pathogens – Infant Participants .............................67
8.1.4.6. Biological Samples – Maternal and Infant Participants............67
8.2. Safety Assessments .................................................................................................68
8.2.1. Participant Electronic Diary – Maternal Participants .................................68
8.2.1.1. Local Reactions – Maternal Participants...................................69
8.2.1.2. Systemic Events – Maternal Participants..................................70
8.2.1.3. Temperature – Maternal Participants ........................................72
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant 
Participants.......................................................................................................72
8.3. Adverse Events and Serious Adverse Events..........................................................72
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8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......73
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................74
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................75
8.3.2. Method of Detecting AEs and SAEs ..........................................................75
8.3.3. Follow-up of AEs and SAEs.......................................................................75
8.3.4. Regulatory Reporting Requirements for SAEs...........................................76
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Investigational Product ..........................................................................76
8.3.5.1. Exposure During Breastfeeding ................................................76
8.3.5.2. Occupational Exposure .............................................................76
8.3.6. Adverse Events of Special Interest.............................................................77
8.3.7. Medical Device Deficiencies......................................................................78
8.3.7.1. Time Period for Detecting Medical Device Deficiencies .........78
8.3.7.2. Follow-up of Medical Device Deficiencies...............................78
8.3.7.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................79
8.3.7.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................79
8.3.8. Medication Errors .......................................................................................80
8.4. Treatment of Overdose............................................................................................81
8.5. Pharmacokinetics ....................................................................................................81
8.6. Pharmacodynamics..................................................................................................81
8.7. Genetics...................................................................................................................81
8.7.1. Specified Genetics ......................................................................................81
8.8. Biomarkers ..............................................................................................................81
8.9. Health Economics ...................................................................................................81
8.10. Procedures – Maternal Participants.......................................................................81
8.10.1. Screening and Vaccination Visit (Clinic; Day -28 to Day 1 – Visit 
1) ......................................................................................................................81
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After 
Vaccination).....................................................................................................86
8.10.3. Delivery (Maternity Unit).........................................................................86
8.10.4. 6-Month-Postdelivery Visit (Clinic or Telephone; 180 to 210 Days 
After Delivery).................................................................................................88
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8.10.5. Unscheduled Reactogenicity Visits..........................................................88
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria –
Maternal Participants .......................................................................................90
8.11. Procedures – Infant Participants............................................................................91
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After 
Birth)................................................................................................................91
8.11.2. Visit 2 – 1-Month Follow-up (Clinic, 28 to 48 Days After Birth) ...........92
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic, 180 to 210 Days After 
Birth)................................................................................................................93
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 
Days After Birth) .............................................................................................94
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days 
After Birth; Infant Participants Born During the First Year of the Study 
Only) ................................................................................................................96
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 
742 Days After Birth; Infant Participants Born During the First Year of 
the Study).........................................................................................................96
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 
Months After Delivery)....................................................................................97
8.11.7.1. RTI Associated With a Medical Visit – Hospital, Home, 
or Clinic Visit ....................................................................................97
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit 
Criteria .............................................................................................................98
8.12. Communication and Use of Technology.............................................................100
9. STATISTICAL CONSIDERATIONS ..............................................................................101
9.1. Estimands and Statistical Hypotheses...................................................................101
9.1.1. Estimands – Infant Participants ................................................................101
9.1.1.1. Efficacy ...................................................................................101
9.1.1.2. Immunogenicity ......................................................................101
9.1.1.3. Safety.......................................................................................102
9.1.2. Estimands – Maternal Participants ...........................................................102
9.1.2.1. Immunogenicity ......................................................................102
9.1.2.2. Safety.......................................................................................103
9.2. Sample Size Determination...................................................................................103
9.3. Populations for Analysis .......................................................................................104
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9.4. Statistical Analyses ...............................................................................................105
9.4.1. Efficacy Analyses .....................................................................................105
9.4.2. Safety Analyses ........................................................................................108
9.4.3. Other Analyses..........................................................................................109
9.4.3.1. Immunogenicity Analyses.......................................................109
9.4.3.2. Healthcare Utilization Analyses..............................................110
9.5. Interim Analyses ...................................................................................................110
9.5.1. Data Monitoring Committee.....................................................................112
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................113
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............113
10.1.1. Regulatory and Ethical Considerations ..................................................113
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................113
10.1.2. Financial Disclosure ...............................................................................114
10.1.3. Informed Consent Process ......................................................................114
10.1.4. Data Protection .......................................................................................115
10.1.5. Dissemination of Clinical Study Data ....................................................115
10.1.6. Data Quality Assurance ..........................................................................117
10.1.7. Source Documents..................................................................................118
10.1.8. Study and Site Closure............................................................................118
10.1.9. Publication Policy...................................................................................119
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................119
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................121
10.2.1. Definition of AE .....................................................................................121
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs).................122
10.2.3. Definition of SAE...................................................................................122
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs.....................123
10.2.5. Reporting of SAEs..................................................................................127
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......128
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10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting............................................130
10.4.1. Definition of AE and Adverse Device Effect (ADE) .............................130
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device 
Effect, and Unanticipated Serious Adverse Device Effect............................130
10.4.3. Definition of Device Deficiency.............................................................131
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................131
10.4.5. Reporting of SAEs..................................................................................134
10.4.6. Reporting of SADEs...............................................................................134
10.5. Appendix 5: Background Factors........................................................................135
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria 
Checklist for MA-RTI Visit – Infant Participants...................................................136
10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only...............138
10.7.1. Informed Consent for the Maternal Participants 18 to <20 Years 
Old..................................................................................................................138
10.7.2. Temperature Measurement and Definition of Fever ..............................139
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants.........139
10.7.3.1. Enrollment of Maternal Participants in the Sentinel 
Cohort..............................................................................................139
10.7.3.2. Conclusion of the Sentinel Cohort ........................................139
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or 
Telephone; 14 to 16 Days After Vaccination).................................139
10.7.3.4. Schedule of Activities for Maternal Participants Enrolled 
in the Sentinel Cohort in Japan........................................................141
10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix –
Applicable to the Gambia and South Africa Only...................................................144
10.9. Appendix 9: Abbreviations .................................................................................145
11. REFERENCES ................................................................................................................148
LIST OF TABLES
Table 1.
Endpoint Events and Definitions in Infant Participants ...........................39
Table 2.
Endpoint Events and Definitions in Maternal Participants.......................43
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Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained....................................................................................................66
Table 4.
Grading Scale for Local Reactions...........................................................70
Table 5.
Grading Scale for Systemic Events ..........................................................71
Table 6.
Ranges for Fever.......................................................................................72
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals 
at an Interim Analysis.............................................................................111
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Indication
Pfizer’s respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSVpreF) 
is a prophylactic vaccine that is being investigated for the prevention of medically attended
RSV-associated lower respiratory tract illness (LRTI) in infants by active immunization of 
pregnant women.
Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given the global burden of disease, maternal immunization offers an attractive 
strategy for infant disease prevention.  Both preclinical studies in animals and interim data 
from a Phase 1/2 study in healthy nonpregnant adults have demonstrated acceptable 
tolerability and safety of RSVpreF.  A robust immune response has also been observed in 
participants from the aforementioned trial. RSVpreF is currently under assessment in healthy 
pregnant women 18 through 49 years of age (Study C3671003: A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blinded Trial to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT04032093).
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
lower respiratory tract illness (MA-LRTI) in infants.  
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Objectives, Estimands, and Endpoints 
Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC): 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:   

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants 
born to maternal 
participants receiving 
1 dose of investigational 
product, the percentage 
of participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

Adverse events (AEs) from birth to 
1 month of age.

Serious adverse events (SAEs) and 
newly diagnosed chronic medical 
conditions (NDCMCs):
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants 
enrolled during the first year of 
the study).
Secondary Efficacy Objectives
– Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of medically attended 
respiratory tract illness 
(MA-RTI) due to RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs 
from vaccination up to 730 days after 
birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 6 months 
of age.
MA-LRTIs due to RSV occurring 181 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth. 
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth. 
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI as confirmed by the 
EAC occurring within 181 days after 
birth.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population. 
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits occurring within 181 days 
after birth.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth. 
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To assess the impact of 
RSVpreF on RSV illness based 
on socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
To assess the effect of RSVpreF 
on healthcare utilization. 
Mean/median composite score 
summarizing healthcare utilization, 
which may include the following: 
number and type of medical visits, length 
of hospital stay, requirement for 
mechanical ventilation, requirement for 
respiratory diagnostic procedures, 
requirement for intravenous (IV) fluids, 
requirement for prescriptions, and 
antibiotic use.
Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimand
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery 
study visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum
neutralizing titers and prefusion F 
immunoglobulin G (IgG) titers 
measured:

before vaccination.

at delivery.
Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
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as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis section [Section 9.2]).  There is no specific case target for 
the additional primary endpoint of severe MA-LRTI. The total enrollment number of 
maternal participants may vary depending on the incidence rate of the primary endpoint in 
the infant participants, the true underlying VE, and a potential early stop for efficacy or 
futility. In the event that efficacy in the infant population is demonstrated at the interim 
analysis, enrollment of maternal participants may continue in order to obtain safety 
evaluations in an adequate number of maternal and infant participants to support vaccine 
registration with national health authorities. 
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It is anticipated that approximately 6900 
mother-infant pairs may be needed to accumulate 124 per-protocol cases.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF will be 120 µg 
(60 µg A and 60 µg B). 
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.  
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study, all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term respiratory 
tract illness (RTI) surveillance and safety oversight to address safety and the possibility of 
conferred enhanced protection (antibody persistence) during a second RSV season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee.
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Planned Duration
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on gestational age (GA) at the time of vaccination and 
when the infant is actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
Data Monitoring Committee
This study will use an external data monitoring committee (E-DMC) to monitor vaccine 
safety and efficacy and study futility.  
Statistical Methods
The primary hypothesis to be tested is that VE with respect to MA-LRTI due to RSV or 
severe MA-LRTI due to RSV in infants within at least 90 days after birth is more than 20%, 
relative to placebo. The 2 primary endpoints will be tested in parallel using a Hochberg 
multiplicity adjustment procedure. VE will be estimated using the exact conditional binomial 
method. There will also be hierarchical testing of the primary endpoints to 120 days, 
150 days, and 180 days, conditional on success of the analysis for the shorter intervals. A 
single interim analysis of the MA-LRTI-due-to-RSV endpoint with the opportunity to stop 
the study for efficacy or futility may be included. At the end of the trial, the RSV vaccine 
may be deemed efficacious if there are 43 or fewer cases of MA-LRTI due to RSV in the 
RSV vaccine group out of the 124 total primary-endpoint cases.  This corresponds to 
estimated VE = 47% with 95.1% confidence interval (CI) = (22%, 64%). For severe 
MA-LRTI, assuming a total of 50 cases occur, the vaccine may be deemed efficacious if 
there are 14 or fewer cases in the RSV vaccine group.  This corresponds to estimated 
VE = 61% with 95.1% CI = (26%, 81%).
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1.2. Schematic for Study Participants
1.2.1. Study Design – Maternal Participants
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1.2.2. Study Design – Infant Participants
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Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
1.2.3. Schedule of Activities for Maternal Participants
Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic or Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current alcohol, tobacco, marijuana, or any illicit drug usage
X
Record vital signs
X
Targeted physical examination performed on the same day or within 
7 days before the vaccination visit
X
Record details of any antenatal and/or postnatal steroid treatment, 
monoclonal antibodies, blood products, or Rho(D) immune globulin
X
X
X
X
Record details of the maternal participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
Review eligibility criteria
X
X
X
Review temporary delay criteria
X
Prevaccination blood draw for serologic assessment (~15 mL) on the 
same day or within 7 days before the vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and measuring devicef
X
Obtain and record baseline assessment of prespecified systemic 
events prior to vaccination in the e-diary
X
Administer investigational product
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic or Telephone
Postvaccination observation (at least 30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic assessment (~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X-------------------------- X
Record AEs, as appropriateh
X-------------------------- X
Record SAEs, as appropriateh
X
X
X
X
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of 
the schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; MA-RTI =
medically attended respiratory tract illness.
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic or Telephone
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.    Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.    AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.    Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and/or the field worker (as per local practice) will record (in an e-diary) a baseline 
assessment of prespecified systemic events prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination (where Day 1 is the 
day of vaccination).  Remind maternal participants that the study staff/field worker may contact them to obtain additional information on events entered 
into the e-diary.  Ask maternal participants to contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 
following vaccination, to determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal participant may be 
referred to the appropriate healthcare facility at the discretion of a field worker if there are any concerns.
g.    Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.    The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected. Please see Section 8.3.1 for reporting requirements 
and timelines.
i.    A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product.
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1.2.3.1. Schedule of Activities for Maternal Participants: RTI Surveillance for Medically Attended Respiratory Tract Illness
Visits (Vaccination Until the End-of-Study Visit)
Visit Description
Assessments of MA-RTIa
Visit Window
As Soon as Possible After Confirmed MA-RTI 
Type of Visit
Telephone
Record details of a confirmed MA-RTI 
X
Details of an acute illness visit AND a report of 1 or more of the following 
RTI signs and symptoms: 

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
X
Obtain standard-of-care records, including local NAAT testing results (if 
applicable)b
X
Record nonstudy vaccine information
X
Record AEs and SAEs, as appropriatec
X
Complete the CRF with details 
X
Abbreviations: CRF = case report form; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness.
a.
Confirmed cases of MA-RTI will be collected from vaccination until the maternal participant completes the study. The assessment of the event would 
involve a telephone call, or a clinic visit if determined by the investigator to be warranted. 
b.
Site staff will review and collect data pertaining to the illness and any local NAAT testing results (RSV, influenza, etc), if available.
c.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  MA-RTI events will not be captured as safety 
events, unless the investigator or an appropriate designee deems them to be related to the investigational product. Please see Section 8.3.1 for reporting 
requirements and timelines.
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1.2.4. Schedule of Activities for Infant Participants
Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the 
First Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-
up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 
Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic 
Clinic 
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Assign infant participant identifier
X
Demography 
X
Collect background factorsc
X
X
X
X
X
X
Collect birth outcome information including 
infant’s birth data and appearance, pulse, 
grimace, activity, and respiration (Apgar) score
X
Obtain and record infant’s length, head 
circumference, and weight
X
X
X
X
(if clinic visit)
X
(if clinic visit)
Physical examination including vital signs
performed within 48 hours after birth
X
Targeted physical examination (record in the site 
source document)
X
X
X
(if clinic visit)
X
(if clinic visit)
Record immune globulins, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole 
blood, packed cells)
X
X
X
X
X
X
Review eligibility
X
Cord blood sample (~10 mL) for serologic 
assessmentd
X
Record AEs, as appropriatee
X
Record NDCMCs and SAEs, as appropriatee
X
X
X
X
X
X
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Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the 
First Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-
up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 
Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic 
Clinic 
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Surveillance reminder contact
Contact with the infant 
participants’ parent(s) or 
legal guardian(s)
approximately every week 
until Visit 3
From Visit 3, contact with the infant participant’s parent(s) or legal guardian(s), 
approximately every 28 to 35 days until the end of the study
Assessment of MA-RTIsf
Assessment of MA-RTI
events during the active RSV 
surveillance period as 
detailed in Section 1.2.4.1 of 
the schedule of activities
Assessment of MA-RTI events as detailed in Section 1.2.4.1 of the schedule of 
activities
Abbreviations: MA-RTI = medically attended respiratory tract illness; NDCMC = newly diagnosed chronic medical condition; RSV = respiratory syncytial 
virus.
a.
Applicable only for infant participants enrolled during the first year of the study.
b.    If medically necessary (eg, during an outbreak or pandemic situation), study visits cannot be conducted in the clinic in accordance with the protocol 
requirements. These visits and associated assessments should be conducted in the home or via telephone. 
c.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV illness. 
d.    Cord blood must be obtained on the day of birth. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical cord has 
been clamped and cut. If cord blood is unavailable, a blood sample may be collected from the infant participant preferably within the first 24 hours but up 
to 7 days after birth. The infant’s weight must be used to determine the volume of blood that can be collected.
e.    The investigator and site staff/field worker will ensure the active elicitation and collection of AEs, NDCMCs, and SAEs through 28 days after birth.  From 
29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected.  An NDCMC is defined as a disease or medical 
condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
f.    A confirmed MA-RTI is defined as an expected study event based on the assessments detailed in the schedule of assessment in Section 1.2.4.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product.
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1.2.4.1. Schedule of Activities for Infant Participants: Respiratory Tract Illness Study Visits During the Study 
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After 
Confirmed MA-RTI and Within 
72 Hours (Preferable) or Up to 10 
Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Surveillance reminder contact
Contact the infant participants’ parent(s) 
or legal guardian(s) approximately every 
week until Visit 3
From Visit 3, contact the infant participants’ parent(s) or legal 
guardian(s), approximately every 28 -35 days until the end of the 
study
Record confirmed MA-RTI as detailed in Appendix 6, 
as appropriate
X
X
X
Record details of the RTI, including 1 or more of the 
following RTI signs and symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid 
breathing for any duration

Cough

Inability to feed for any duration because of 
respiratory symptoms

Apnea

Any other respiratory symptom of concern 
X
X
X
Obtain standard-of-care records and complete CRFc
X
X
X
Record local NAAT testing results, if performed and 
availabled
X
X
X
Perform RTI study visit, record targeted assessment
results (heart rate, respiratory rate, SpO2, chest wall 
indrawing), and collect nasal swab (for RT-PCR)e
X
X
Record concomitant medication associated with the 
treatment of the MA-RTI
X
X
X
Collect background factors associated with MA-RTIf.
X
X
X
Record immune globulins, monoclonal antibodies (eg, 
Synagis), or blood products (eg, whole blood, packed 
cells)
X
X
X
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After 
Confirmed MA-RTI and Within 
72 Hours (Preferable) or Up to 10 
Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Record AEs , NDCMCs, and SAEs, as appropriateg
X
X
X
Compile MA-RTI visit source documentation upon 
request by adjudication committee (qualifying 
RSV-positive cases only)
X
X
Abbreviations: CRF = case report form; ICU = intensive care unit; IV = intravenous; MA-LRTI = medically attended lower respiratory tract illness; 
MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; NDCMC = newly diagnosed chronic medical 
condition; RSV = respiratory syncytial virus; RTI = respiratory tract illness; RT-PCR = reverse transcription–polymerase chain reaction; 
SpO2 = oxygen saturation.
a.
If the infant participant is reported to be experiencing or has had an MA-RTI from birth until Visit 3, the site should arrange a study visit as soon as 
possible and within 72 hours (preferable) or up to 10 days. Ideally, the RTI study visit will be conducted at the investigational study site; however, it is 
possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit 
where the infant participant is residing.
B
If the infant participant is reported to be experiencing or has had an MA-RTI associated with severe LRTI criteria or been hospitalized for an RTI from 
Visit 3 until the end of study participation, the site should arrange a visit as soon as possible and within 72 hours (preferable) or up to 10 days of site 
awareness. Ideally, assessment of these potential endpoint events (hospitalization due to RTI or severe MA-LRTI) will be conducted at the investigational 
study site; however, it is possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or 
the site staff may visit where the infant participant is residing. 
Note: For nonsevere MA-RTIs, a telephone contact with the infant participants’ parent(s) or legal guardian(s) is acceptable to complete the study visit.
c.
Obtain case records, including details of hospitalization, ICU stays, use of oxygen, IV fluids usage, etc.
d.
The site staff/field worker will review and collect data related to any local NAAT testing results, if performed and available.
e.
The site staff/field worker will collect nasal swabs for confirmed MA- RTIs, including confirmed cases of hospitalizations due to an RTI and severe MA-
LRTIs.
f.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV. This will be collected 
for all MA-RTI events reported.
g. 
The investigator and site staff/field worker will ensure the active elicitation and collection of NDCMCs and SAEs through the end-of-study visit for the 
infant participant. From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected. An NDCMC is defined 
as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma). Note: A 
confirmed MA-RTI will not be captured as a safety event, unless the investigator or an appropriate designee deems it to be related to the investigational 
product.
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2. INTRODUCTION
Prevention of RSV disease in young infants is a significant unmet medical need globally.  
RSV is the leading cause of bronchiolitis and viral pneumonia in infants and can lead to fatal 
respiratory distress, especially in those with risk factors including premature infants with 
underlying cardiopulmonary disease, or in the absence of effective healthcare systems.1
However, most cases of RSV disease occur in healthy, full-term infants without risk factors.2
Worldwide, RSV kills approximately 118,200 children annually, with about half of those 
deaths occurring in infants under 6 months of age, and the majority of those occurring in 
resource-limited countries.3,4 In the United States, RSV is the leading cause of infant 
hospitalization, with more than 60,000 hospitalizations of children 12 months of age and 
younger annually.5,6  There is increasing evidence that the link between severe RSV disease 
in infancy and wheezing later in childhood may be causal.7,8  Like influenza, RSV infection 
follows a seasonal pattern, causing illness primarily in the cooler months of the year in 
temperate regions and during the wet season in tropical countries with seasonal rainfall.9  
Infection is essentially universal by the time children reach 2 years of age.10
Currently, there is neither specific treatment for RSV infection nor a vaccine to protect 
against RSV disease.  Treatment consists primarily of supportive care.  A prophylactic 
humanized monoclonal antibody, palivizumab (Synagis, AstraZeneca), targeting the RSV F 
glycoprotein is available for prevention of severe RSV disease in young infants at increased 
risk.11  Limitations of its use include its high cost12 and requirement of multiple monthly 
injections,13 and so it remains recommended for use only in very premature infants and 
others at increased risk of severe illness.6,14
Nevertheless, the protective effect of Synagis provides definitive proof of principle that 
serum neutralizing antibody directed against the F protein can provide clinically meaningful 
protection against RSV lower respiratory tract disease in young infants.15  Furthermore, it is 
well known that in other disease settings, antibodies transferred from mothers to their fetuses 
across the placenta can reduce infant disease early in life,16,17,18,19,20,21 suggesting that 
maternal immunization is a reasonable approach to RSV disease prevention among young 
infants.
There are 2 antigenic variants of RSV, namely, RSV subgroup A (RSV A) and RSV 
subgroup B (RSV B).  The RSV vaccine being investigated in this study is a bivalent vaccine 
composed of stable RSV prefusion F antigens representing the 2 subgroups to help ensure the 
broadest coverage against RSV illness.
RSVpreF is a prophylactic vaccine being developed to prevent medically attended
RSV-associated LRTI in infants by active immunization of pregnant women.
2.1. Study Rationale 
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given a global burden of disease in the millions of cases each year, maternal
immunization offers an attractive strategy for infant disease prevention.  Both preclinical 
studies in animals and interim data from a Phase 1/2 study in healthy nonpregnant adults 
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have demonstrated acceptable tolerability and safety of RSVpreF.  A robust immune 
response has also been observed in the population of the aforementioned trial, at 1 month 
after vaccination. The combined RSV A and B serum neutralization geometric mean titers 
(GMTs) have been shown to be 12 to 20 times higher than those with 100 μg/mL of
palivizumab, the concentration of the monoclonal antibody that is known to provide near to 
complete protection of high-risk infants from severe RSV disease.22,23 RSVpreF is currently 
under assessment in healthy pregnant women 18 through 49 years of age (Study C3671003, 
A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093).
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
RSV-associated LRTI in infants.  
2.2. Background 
RSV is an important cause of morbidity and mortality worldwide, with a substantial burden 
of disease borne by young infants.  Rates of severe RSV illness are highest in infants 
6 months of age, with a peak in hospitalization between 1 and 2 months of life, though the 
highest case-fatality rates are observed in the neonatal period (<1 month).2 Infants born 
prematurely and those with underlying cardiac or pulmonary disease are at further increased 
risk of severe clinical disease due to RSV.  A 2017 retrospective case analysis that examined 
RSV mortality data from 23 countries demonstrates the global nature of the seriousness of 
RSV disease, with significant morbidity and mortality occurring in both lower- and 
middle-income countries (LMICs) and high-income countries.3,4
No specific treatments for RSV exist, and available prophylactic measures (ie, RSV 
monoclonal antibody) are limited to use in only those infants at highest risk; additionally, in 
LMICs, use of available RSV prophylaxis is cost-prohibitive.  While active immunization 
against RSV in infants might be an option, multiple efforts, extending over half a century, to 
develop a safe and effective RSV vaccine to protect infants from disease have yielded little 
success.  The early peak of disease presents a further obstacle to an active vaccination 
strategy for infants.  Given these challenges, maternal immunization to protect infants early 
in life offers an attractive strategy for infant disease prevention.  
The present RSV vaccine efforts were initiated in early 2014 based on a new scientific 
discovery (determination of the RSV prefusion F crystal structure)24 and a changing 
regulatory and policy environment that today supports the development of vaccines for 
maternal immunization to protect very young infants.  The trimeric RSV F surface 
glycoprotein in a prefusion conformation is now known to be the primary target of 
neutralizing antibodies and is the basis for the engineered antigens in Pfizer’s vaccine 
candidate.   Applying structure-guided vaccine design, Pfizer has developed a stabilized RSV 
prefusion F vaccine candidate.  The core hypothesis underlying Pfizer’s RSV vaccine 
development effort for prevention of infant disease is that vaccine antigens based on RSV 
prefusion F, when administered to pregnant women in the second or third trimester of 
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pregnancy, will elicit sufficiently high neutralizing antibody titers that, when the antigens are 
actively transferred transplacentally to the fetus, will protect infants against RSV disease. 
The aim is for neutralizing antibody levels to be at sufficient levels such that infants will be 
protected from birth and possibly through their first RSV season.
2.3. Benefit/Risk Assessment
RSVpreF is being evaluated in ongoing clinical studies.  Pfizer’s maternal immunization 
approach circumvents the risk of vaccine-mediated disease enhancement that was observed 
in the 1960s following direct immunization of RSV-naive infants with a formalin-inactivated 
RSV vaccine (FI-RSV).25  FI-RSV elicited a predominantly nonneutralizing antibody 
response and a Th2-biased cell-mediated response, both of which are considered potential 
contributing factors to disease enhancement.26  During preclinical studies, in a standard 
cotton rat infectious RSV challenge model, FI-RSV showed pathological signs of causing 
disease enhancement, and the current Pfizer vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease enhancement has not been reported to occur in 
RSV-experienced individuals after immunization with any RSV vaccine candidate.  Because 
pregnant women are universally RSV-experienced, they are not at risk for a 
disease-enhancing immune response to the vaccine that could exacerbate infection in 
themselves or their infants.  A previous study of maternal immunization with a Wyeth (later 
merged with Pfizer) investigational RSV vaccine (PFP-2) showed an acceptable safety 
profile, even though this candidate contained a postfusion RSV F antigen that elicited a 
relatively weak RSV-neutralizing antibody response and a higher nonneutralizing 
RSV-binding antibody response in pregnant women.27  A recently completed Phase 3 
maternal RSV trial (Novavax) with an RSV vaccine containing F not stabilized in the 
prefusion form, given to over 4600 healthy pregnant volunteers, showed a similar safety 
profile in the RSV vaccine and placebo groups.28
Vaccination with the RSV prefusion F antigens elicits a higher ratio of neutralizing to 
nonneutralizing antibodies, more closely matching the profile in naturally exposed 
individuals.  The safety profile of RSVpreF observed to date is similar to that of prior RSV F 
subunit vaccines tested in RSV-experienced adults.
There are limited data on the global burden of maternal RSV infection, likely in part because 
of infrequent diagnostic testing. However, in one multisite study, RSV-associated disease in 
pregnancy was shown to result in prolonged hospitalization and an increased likelihood of 
preterm birth in women who tested RSV-positive.29 It is possible that vaccination may 
benefit the pregnant women who receive it. RTI in mothers who receive RSVpreF will be 
explored in this study.  The benefit of maternal vaccination is accrued to the infant by means 
of transplacental antibody transfer.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the investigator’s brochure (IB), which is the 
single reference safety document (SRSD) for this study. 
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Infant Participants
The study objectives and endpoints for infant participants employ the event definitions in 
Table 1.
Table 1.
Endpoint Events and Definitions in Infant Participants
Study 
Endpoints/Assessments
Study Definitions
Medically attended visit
Infant participant has been taken to or seen by a healthcare provider 
(eg, outpatient or inpatient visit, emergency room, urgent care, or home 
visit)
MA-RTI visit for infant 
participant
A medically attended visit AND 1 or more of the following RTI signs and 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any 
duration

Cough

Inability to feed for any duration because of respiratory symptoms

Apnea

Any other respiratory symptom of concern 
RSV-positive testa

RSV RT-PCR–positive test result by Pfizer central laboratory
OR

RSV-positive test result by certified laboratory with NAAT for RSV
MA-RTI due to RSVb

An MA-RTI visit 
AND

RSV-positive test result as described in Section 8.1.1.1
MA-LRTI due to any cause

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age], 
≥50 bpm for ≥2 months to 12 months of age, or ≥40 bpm for ≥12 
months to 24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
MA-LRTI due to RSVb

Infant with an MA-RTI visit 
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age] or 
≥50 bpm for ≥2 to 12 months of age, or ≥40 bpm for ≥12 months to 
24 months of age) OR

SpO2 <95% OR

Chest wall indrawing 
AND 

RSV-positive test result as described in Section 8.1.1.1
Hospitalized RTI due to RSVb
An RTI due to RSV that results in hospitalization
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Table 1.
Endpoint Events and Definitions in Infant Participants
Study 
Endpoints/Assessments
Study Definitions
Severe MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥70 bpm for <2 months of age [<60 days of age], 
≥60 bpm for ≥2 months to 12 months of age, or ≥50 bpm for ≥12 
months to 24 months of age) OR

SpO2 <93% OR

High-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive) OR

ICU admission for >4 hours OR

Failure to respond/unconscious 
AND

RSV-positive test result as described in Section 8.1.1.1
Protocol-defined primary 
endpoint

Any MA-LRTI or severe MA-LRTI due to RSV as determined by an 
EAC
Abbreviations: bpm = breaths per minute; EAC = endpoint adjudication committee; ICU = intensive care 
unit; MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically attended 
respiratory tract illness; NAAT = nucleic acid amplification technology; RR = respiratory rate; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness; SpO2 = oxygen saturation.
a.
RSV-positive testing is defined as a positive RSV test (see Section 8.1.1.1) conducted on a sample 
obtained during the medically attended visit or within 10 days (where Day 1 is the day of the MA-RTI 
visit) as detailed in Section 8.11.7.
b.
The EAC will determine if the endpoint criteria have been met upon review of the site source 
documentation from the MA-RTI visit and RTI study visits, including all available RSV test results . 
Study Objectives – Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:   

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants born 
to maternal participants 
receiving 1 dose of 
investigational product, 
the percentage of 
participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

AEs from birth to 1 month of age.

SAEs and NDCMCs:
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants enrolled 
during the first year of the study).
Secondary Efficacy Objectives
–
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with protocol-
defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI due to 
RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs from 
vaccination up to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 6 months of 
age.
MA-LRTIs due to RSV occurring 181 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after 
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
Hospitalization due to RSV occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause MA-LRTI.
MA-LRTIs due to any cause occurring 181 
to 730 days after birth.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI as confirmed by the 
EAC occurring within 181 days after birth.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned MA-RTI
visits occurring within 181 days after 
birth.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
To assess the impact of RSVpreF 
on RSV illness based on 
socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors (eg, 
breastfeeding, maternal smoking, number 
of household members).
To assess the effect of RSVpreF 
on healthcare utilization.
Mean/median composite score 
summarizing healthcare utilization, which 
may include the following: number and 
type of medical visits, length of hospital 
stay, requirement for mechanical 
ventilation, requirement for respiratory 
diagnostic procedures, requirement for IV 
fluids, requirement for prescriptions, and 
antibiotic use.
3.2. Maternal Participants
The study objectives and endpoints for maternal participants employ the event definitions in 
Table 2.
Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
Maternal medically attended visit
The maternal participant reports a visit with a healthcare 
provider (outpatient or inpatient visit, emergency room, 
urgent care, or home visit)
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Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
MA-RTI visit maternal participant
A medically attended visit AND 1 or more of the following 
RTI signs and symptoms:

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
Abbreviations: MA-RTI = medically attended respiratory tract illness; RTI = respiratory tract illness.
Study Objectives – Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimands
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery study 
visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum neutralizing 
titers and prefusion F IgG titers 
measured:

before vaccination.

at delivery.
3.3. Protocol-Defined Efficacy Endpoints 
All infant participants experiencing an MA-RTI will have an RTI study visit as detailed in
Section 8.1.  This protocol will use an independent EAC to determine whether certain 
investigator-reported events meet the definition of disease-related efficacy endpoints, using 
predefined endpoint criteria as summarized in Table 1. Members of this EAC will be blinded 
to the vaccine assignment to allow for unbiased assessments.
Recognizing that RSV disease is a dynamic illness, sites will be instructed to submit all 
available source documentation for adjudication from the MA-RTI visit and to record data 
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from the worst day of illness in the electronic case report form (eCRF).  The EAC will 
determine if the endpoint criteria have been met upon review of the site source
documentation from the MA-RTI visit, including data collected at the RTI study visit, and all 
available RSV testing.  Further information about the EAC will be detailed in the 
adjudication charter, including specific descriptions of the scope of its responsibilities and 
the process and definitions to review and assess study endpoints.
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition and 
constitute a study endpoint will not be recorded as AEs.  For those AEs that are handled as 
disease-related efficacy endpoints, a data monitoring committee (DMC) will conduct 
unblinded reviews on a regular basis throughout the trial (see Data Monitoring Committee,
Section 9.5.1). 
Nonendpoint events (eg, an event that is determined not to be an MA-RTI) must be evaluated 
for safety reporting as per the protocol requirements.  Any AE that is adjudicated by the EAC
to not meet any endpoint criteria will be reported back to the investigator site of incidence; 
the investigator at the site must evaluate the event for safety as described in Appendix 2 of 
this protocol.  If the event is classified as serious, the investigator’s SAE awareness date in 
this instance is identified as the date on which the investigator site receives the nonendpoint 
SAE back from the EAC.  Handling these SAEs in this manner will allow Pfizer to meet its 
sponsor reporting obligations to regulatory authorities upon receipt of such SAEs.
Any events that remain unadjudicated at the annual safety report cutoff date will not be 
included in the safety tables of the report.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons. 
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of 
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis (Section 9.2). There is no specific case target for the 
additional primary endpoint of severe MA-LRTI. The total enrollment number of maternal 
participants may vary depending on the incidence rate of the primary endpoint in the infant 
participants, true underlying VE, and a potential early stop for efficacy or futility. In the 
event that efficacy in the infant population is demonstrated at the interim analysis, enrollment 
of maternal participants may continue in order to obtain safety evaluations in an adequate 
number of maternal and infant participants to support vaccine registration with national 
health authorities. 
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Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It is anticipated that approximately 
6900 mother-infant pairs may be needed to accumulate 124 per-protocol cases.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF for this study will be 
120 µg (60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.  
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term RTI 
surveillance and safety oversight to address safety and the possibility of conferred enhanced 
protection (antibody persistence) during a second RSV season. 
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. In addition, this study will use an 
E-DMC to monitor vaccine safety and efficacy and study futility.  
4.1.1. Approximate Duration of Participation for Each Participant
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on GA at the time of vaccination and when the infant is 
actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth. 
4.1.2. Approximate Number of Participants
Healthy pregnant women will be randomly assigned to a study intervention. It is anticipated 
that approximately 6900 mother-infant pairs may be needed to accumulate 124 per-protocol 
cases as defined in Section 9.2 of the protocol.  Enrollment will be monitored to ensure that 
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participants will be recruited from both the northern and southern hemispheres. Enrollment 
may vary depending on the incidence in the placebo group, the true underlying VE, the 
dropout rate, and a potential early stop for VE or futility.
4.2. Scientific Rationale for Study Design
Refer to Section 2.1.
4.3. Justification for Dose
The final dose and formulation of RSVpreF selected for use in this study is based on the 
safety and immunogenicity data from the ongoing C3671003 maternal immunization study
(A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093) and the first-in-human (FIH) study C3671001.
The FIH study was designed to describe the safety, tolerability, and immunogenicity of 
6 RSVpreF candidates with bivalent formulations (RSV A and B) at 3 escalating dose levels 
of 60 µg (30 µg A and 30 µg B), 120 µg (60 µg A and 60 µg B), and 240 µg (120 µg A and 
120 µg B) of the RSV prefusion F antigen, with or without Al(OH)3, when administered 
alone or concomitantly with seasonal inactivated influenza vaccine.  The study utilizes a 
sentinel cohort (N=168; Phase 1) and an expanded cohort (N=1014; Phase 2).  Nonpregnant 
female and male study participants of 2 age groups, 18 through 49 years of age and 
50 through 85 years of age, were enrolled into both cohorts.  The age groups are being run in 
parallel. 
A recent interim analysis of participants 18 through 49 years of age, including safety and 
tolerability (n=533) and immunogenicity (n=513) data up to 1 month after vaccination in the 
expanded cohort and additional immunogenicity data up to 3 months after vaccination in the 
sentinel cohort, has shown the RSVpreF candidate to be immunogenic and well tolerated. 
Local reactions and systemic events were noted to be predominantly mild or moderate across 
all doses and formulations, which is consistent with the current safety profile. The safety 
results from this planned interim analysis of healthy male and nonpregnant female 
participants 18 through 49 years of age are consistent with those from the sentinel-cohort 
analysis and indicate that RSVpreF has an acceptable safety profile and is well tolerated.
The immunogenicity results showed that RSVpreF elicited neutralizing titer geometric mean 
fold rises (GMFRs) of 10 to 20, 1 month after vaccination, depending on the formulation. 
Similarly, across all dose levels, with and without Al(OH)3, RSVpreF elicited high 1-month-
postvaccination RSV A and RSV B neutralizing GMTs. Overall, RSVpreF elicited anti–
prefusion F immunoglobulin G1 (IgG1) responses that paralleled the elicited 
RSV-neutralizing responses. The ratio of RSV 50% neutralizing antibody titer GMFRs to 
prefusion RSV F binding IgG1 titer GMFRs (calculated with combined data for subgroups A 
and B) for the sentinel and expanded 18 through 49 years of age cohorts combined ranged 
from 0.62 to 0.76. The IgG1 and neutralization responses were similar in antigen-level dose
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response, in equivalence of RSV A titer GMFRs to RSV B titer GMFRs, and in a lack of 
effect of Al(OH)3. 
The high ratio of RSV-neutralizing antibody titer GMFRs to prefusion F–binding titer 
GMFRs elicited by Pfizer’s RSVpreF candidate indicates that most of the elicited antibody 
can neutralize the virus. It is assumed that this reflects the ability of the antibodies to prevent 
RSV disease in immunized participants and, in the case of maternal immunization, prevent 
disease in their infants.
The primary mechanism for protection of infants by the RSV maternal vaccine is 
neutralization of the virus by transplacentally transferred antibody, which is increased by 
immunization.  Maternal antibody decays exponentially in infants.  Therefore, it is 
anticipated that higher titers of transferred neutralizing antibodies will provide greater levels
and durations of infant protection.  Results from the C3671001 FIH trial were used to 
determine the doses and formulations that are currently under investigation in the Phase 2b 
maternal immunization study: 120 µg or 240 µg of RSVpreF with or without Al(OH)3. 
These doses are expected to provide the greatest potential level of transplacental antibody 
transfer to infants and, therefore, the greatest potential benefit.  The dose and formulation of 
RSVpreF for the Phase 3 study was determined by the evaluation of the 1-month safety, 
tolerability, and immunogenicity results from the C3671003 maternal Phase 2b trial,
including infant RSV-neutralizing titers at birth.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last infant participant in the 
study. The study may also be terminated earlier for efficacy or futility as described in
Section 9.5.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria 
5.1.1. Inclusion Criteria – Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply 
(refer to the investigator site file [ISF] for further eligibility details):
Note: In countries/locales where study procedures used to determine eligibility criteria 
(eg, ultrasound examination, human immunodeficiency virus [HIV] testing, syphilis testing) 
are not performed as part of routine prenatal care, they must be performed as part of this 
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clinical trial and reviewed by the investigator or qualified designee within 28 days prior to 
randomization.  Maternal participants must provide informed consent prior to 
performing any procedures, including those that are being done exclusively to meet 
study eligibility criteria.
Note: Country-specific modifications associated with the study eligibility criteria are 
documented in Appendix 7 and Appendix 8.
Age and Sex:
1. Healthy women ≥18 and ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of 
gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, 
who are at no known increased risk for complications. 
Note: GA must be based upon 1 of the following composite criteria based on timing and 
availability of data on the last menstrual period (LMP) and an ultrasound examination 
performed in the first or second trimester.30  The earliest ultrasound data available during 
the current pregnancy should be used to establish GA:
a.
First-trimester data available (data obtained at ≤13 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a first-trimester ultrasound examination.

If there is a discrepancy of >5 days between the LMP-determined GA and an 
ultrasound result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA 
should be determined using the first-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and an 
ultrasound result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, 
then the GA should be determined using the first-trimester ultrasound result.
b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a second-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and the 
ultrasound result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >10 days between the LMP-determined GA and the 
ultrasound result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
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
If there is a discrepancy of >14 days between the LMP-determined GA and the 
ultrasound result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
Type of Participant and Disease Characteristics:
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Receiving prenatal standard of care based on country requirements.
4. Had an ultrasound examination performed at ≥18 weeks of pregnancy with no significant 
fetal abnormalities observed, based on the investigator’s judgment. 
5. Determined by medical history, physical examination, and clinical judgment to be 
appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) 
surface antigen test during this pregnancy and prior to randomization (Visit 1). 
7. Intention to deliver at a hospital or birthing facility where study procedures can be 
obtained. 
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol OR
11. If the maternal participant is illiterate, a thumbprinted informed consent must be 
obtained, which must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process confirming that the maternal participant 
has been informed of all pertinent aspects of the study.
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5.1.2. Inclusion Criteria – Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a 
thumbprinted informed consent must have been obtained, which must have been signed 
and dated by an impartial witness who was present throughout the entire informed 
consent process confirming that the maternal participant/parent(s)/legal guardian(s) has 
been informed of all pertinent aspects of the study for herself (maternal participant) and 
her fetus/infant prior to taking part in the study.  
Note: Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements. 
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
5.2. Exclusion Criteria 
5.2.1. Exclusion Criteria – Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not 
available, the BMI at the time of the first obstetric visit during the current pregnancy may 
be used.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any related 
vaccine.
4. Current pregnancy resulting from in vitro fertilization.  Participants known to have used 
clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are 
permitted.
5. Current pregnancy complications or abnormalities at the time of consent that will 
increase the risk associated with the participation in and completion of the study, 
including but not limited to the following:

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.
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
Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated 
hypothyroidism.  This also includes disorders of glucose intolerance (eg, diabetes 
mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if 
uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the 
investigator’s judgment, that will increase the risk associated with the participation in and 
completion of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks’ gestation.

Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or significant congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the maternal 
participant’s participation in, and completion of, the study or could preclude the 
evaluation of the maternal participant’s response.
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment.  
9. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to 
consent and/or during study participation.
11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of 
systemic corticosteroids for >14 days within 28 days prior to study enrollment.  
Prednisone use of <20 mg/day for ≤14 days is permitted. Inhaled/nebulized, 
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
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12. Current alcohol abuse or illicit drug use.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before 
investigational product administration, or planned receipt through delivery, with 
1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt 
during study participation.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
5.2.2. Exclusion Criteria – Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
2. Receipt of investigational or approved monoclonal antibodies against RSV.
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and if no other exclusion criteria are met.  
The prevaccination blood draw and vaccination should take place on the same day. In the 
event that this is not possible, the prevaccination blood draw is also permissible within 7 days 
before the vaccination visit.

Current febrile illness (body temperature ≥100.4°F [≥38°C]) or other acute illness within 
48 hours before investigational product administration.

Diagnosed malaria within the last 7 days prior to investigational product administration.

Receipt of any inactivated vaccine within 14 days or any live vaccine within 28 days 
before investigational product administration. Note: tetanus, diphtheria, and acellular 
pertussis vaccine (Tdap) coadministration may be excluded from temporary delay criteria 
based on data from the C3671004 study (A Phase 2b, Placebo-Controlled, Randomized, 
Observer-Blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 
Respiratory Syncytial Virus (RSV) Vaccine When Administered Concomitantly With 
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Tetanus, Diphtheria, and Acellular Pertussis Vaccine (Tdap) in Healthy Nonpregnant 
Women 18 Through 49 Years of Age; ClinicalTrials.gov identifier: NCT04071158).

If systemic corticosteroids (equivalent of ≥20 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical 
study but are not subsequently randomly assigned to investigational product. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
For this study, the investigational product(s) are RSVpreF and placebo (lyophile match).
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine 
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.  The
RSV drug product will be 120 µg of the RSV prefusion F antigen.  The drug product is 
supplied as a lyophilized white cake in a 2-mL glass vial, with a 13-mm lyophilization 
stopper, aluminum overseal, and flip-off cap. The drug product will be reconstituted by a 
diluent consisting of sterile water in a prefilled syringe (PFS). The lyophilized drug product 
contains excipients that, after reconstitution, will yield a solution as detailed in the IB.
The fill volume of the drug product vial and diluent PFS are designed such that the intended 
vaccine dose is delivered by injecting the entire contents of the syringe.
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6.1.2. Placebo
Placebo will be a lyophile match to the vaccine, which will consist of excipients matched to 
those used in the RSVpreF vaccine formulation, minus the active ingredients. 
The physical appearance of the reconstituted RSVpreF and placebo will be matched, and the 
study will be conducted in a double-blinded manner.
The fill volume of the placebo vial and diluent PFS is designed such that the intended 
placebo dose is delivered by injecting the entire contents of the syringe.
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
6.1.3. Administration
Maternal participants will receive 1 dose of investigational product at the vaccination visit 
(Day 1) in accordance with the study’s SoA.  The investigational product will be 
administered intramuscularly by injecting the entire contents of the syringe into the deltoid 
muscle, preferably of the nondominant arm, unless medically contraindicated, in which case 
the injection may be administered in the dominant arm. Investigational product
administration will be performed by appropriately designated study staff at the investigator 
site.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance. 
Investigational product administration details will be recorded on the case report form (CRF).
6.1.4. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluent for the RSV
vaccine or placebo, consisting of sterile water PFS only.
Instructions for medical device use are provided in the investigational product manual (IP 
manual).
Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the unblinded study personnel throughout the 
study.
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Please refer to Section 8.3.7 for details. 
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention, as applicable for 
temperature-monitored shipments. 
2. Only maternal participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking days must indicate the minimum and maximum 
temperature since previously documented for all site storage locations upon return to 
business.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  All study interventions will be 
accounted for using an investigational product accountability form/record.  
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
6. Study interventions should be stored in their original containers and in accordance with 
the labels.
7. See the IP manual for storage conditions of the study intervention once reconstituted.
8. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use of 
the study intervention after the temperature excursion. Use of the study intervention prior 
to Pfizer approval will be considered a protocol deviation. Specific details regarding the 
definition of an excursion and information the site should report for each excursion will 
be provided to the site in the IP manual.
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9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
Additional details about accountability, storage, destruction, and excursion reporting can 
be found in the IP manual.
6.2.1. Preparation and Dispensing
Refer to the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
Investigational product and placebo will be prepared by qualified site personnel according to 
the IP manual.  The investigational product will be administered only to maternal participants 
who are blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Blinding of Study Site Personnel 
This study is a double-blinded study, as the physical appearance of RSVpreF and placebo 
will be matched. The maternal participant, investigator, study coordinator, and all site staff 
will be blinded. 
Please refer to the IP manual for further details.
6.3.2. Blinding of the Sponsor
The sponsor study team members will be blinded throughout the study to the vaccine 
assignments of all participants enrolled in the study. 
Laboratory personnel performing the serology and virology assays will remain blinded to 
vaccine assigned/received throughout the study.
6.3.3. Allocation to Investigational Product
Allocation of maternal participants to vaccine groups will proceed through the use of an 
interactive response technology (IRT) system (interactive Web-based response [IWR]).  The 
site personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the maternal participant number.  The site personnel will then be 
provided with a vaccine assignment, randomization number, and dispensable unit (DU) or 
container number as investigational product is being supplied via the IRT system.  The IRT 
system will provide a confirmation report containing the maternal participant number, 
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randomization number, and DU or container number assigned. The confirmation report must 
be stored in the site’s files. 
Note: Maternal participants will be randomized to a vaccine group as described above.  The 
infants of the maternal participants will be assigned an infant participant number at birth.
Investigational product will be dispensed and administered at study Visit 1 summarized in 
the SoA. 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Maternal participants will be assigned to receive investigational product according to the 
randomization scheme.  Investigators will remain blinded to the investigational product 
assigned to each maternal participant throughout the course of the study.
6.3.4. Breaking the Blind 
The study will be maternal participant and investigator blinded.
At the initiation of the study, the investigator will be instructed on the method for breaking
the blind for an individual participant.  The method will be an electronic process.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the participant.  The 
investigators should make every attempt to contact a member of the sponsor’s study team 
prior to breaking the blind.  When the blinding code is broken, the reason must be fully
documented and entered on the CRF.  
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy 
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal Participants

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study.

Receipt of blood/plasma products or Ig, from 60 days before investigational product 
administration, or planned receipt through delivery, with 1 exception, Rho(D) immune 
globulin (eg, RhoGAM), which can be given at any time.

Immunosuppressive therapy is prohibited during the course of the study.
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
Nonstudy vaccines may not be given concomitantly with the investigational product or 
within 7 days after investigational product administration (Day 1 to Day 7), except if 
medically necessary (eg, during an outbreak or pandemic situation).  
Note: For licensed Tdap, coadministration may be permissible based on data from the 
C3671004 study.
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal Participants

Licensed vaccines (including influenza vaccine and Tdap) may be given during the study 
starting 7 days after investigational product administration (Day 8) as per local 
recommendation for immunization in pregnant women. If medically necessary (eg, 
during an outbreak or pandemic situation), influenza vaccine, Tdap, or other vaccines 
may be given at any time.
Note: Tdap coadministration may be permissible based on data from the C3671004 study.

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. Prednisone use of <20 mg/day for ≤14 days prior to the administration of 
investigational product is permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during participant participation in the 
study.
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following vaccinations and treatments for maternal participants would require reporting 
in the CRF during the study: 

Details of any vaccinations given at any time during the pregnancy through the final 
study visit will be collected and recorded in the CRF.

Details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given to the maternal participant at any time during the 
pregnancy or during the study will be collected and recorded in the CRF.

Any prescribed medications taken to treat medically attended respiratory illnesses from 
enrollment until the final study visit will be recorded in the CRF.
Concomitant medications not meeting the criteria above will be assessed but not documented 
on the CRF.
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6.5.4. Permitted Concomitant Vaccinations and Treatments – Infant Participants

Routine treatments, routine vaccinations, and routine procedures 
(eg, circumcision) are permitted at any time according to national recommendations or 
medical standard of care or accepted practice.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies
are permitted during infant participant participation in the study.

Local anesthetic may be applied to the site of the blood draw, as appropriate.
6.5.5. Recording Nonstudy Vaccinations and Concomitant Medications – Infant 
Participants
The following CRF reporting guidelines are applicable to treatments given to infant 
participants during the study:

Details of any Ig (including monoclonal antibodies [eg, Synagis] or immune globulin 
[eg, hepatitis B immune globulin (HBIG)]) or blood products (eg, whole blood, packed 
cells) given to the infant participant will be collected from the time of birth until the final 
study visit and recorded in the CRF.

Any prescribed medication taken to treat medically attended respiratory illnesses from 
the time of birth until the final visit.  

Details of IV fluids given during an MA-RTI will be collected and recorded in the CRF.
6.6. Dose Modification 
Dose modification is not applicable in this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Discontinuation of study intervention is not applicable in this study.
7.2. Participant Discontinuation/Withdrawal From the Study 
A maternal participant may withdraw from the study at any time at her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. An infant participant may withdraw from the study at 
any time at the request of his or her parent(s) and/or legal guardian(s) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.
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The participants, or, if appropriate, their parent(s) and/or legal guardian(s), should be
questioned regarding their reason for withdrawal. The participant will be permanently
discontinued from the study at that time.
If a maternal participant withdraws from the study, she may request destruction of any 
remaining samples taken and not tested, but data already generated from the samples will 
continue to be available and may be used to protect the integrity of existing analyses. If an 
infant participant is withdrawn from the study, his or her parent(s) and/or legal guardian(s) 
may request destruction of any remaining samples, but data already generated from the 
samples will continue to be available, and may be used to protect the integrity of existing 
analyses. The investigator must document any such requests in the site study records and 
notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
Participants who withdraw after randomization will not be replaced.
7.3. Withdrawal of Consent 
Maternal participants and parent(s)/legal guardian(s) of infant participants born to maternal 
participants who request to withdraw consent from any further study contact or with persons 
previously authorized by the participant to provide this information should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible.  The withdrawal of consent should be explained in detail in the medical records by 
the investigator, as to whether the withdrawal is only from study procedures and/or 
postvaccination study follow-up. If the participant (maternal or infant) only withdraws from 
a study procedure, safety information should be completed until the end of the study, unless 
consent for further contact has been withdrawn.  In the event that vital status (whether the 
participant is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
The regulatory and ethical considerations for this study, including the informed consent 
process, are summarized in Section 10.1.1 and Section 10.1.3.
7.4. Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
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The following actions must be taken if a participant fails to return to the clinic for a required
study visit:

The site must attempt to contact the participant, or parent(s) and/or legal guardian(s), and 
reschedule the missed visit as soon as possible and counsel the participant or parent(s) 
and/or legal guardian(s) on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or parent(s) and/or legal guardian(s) wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record.

Should the participant or parent(s) and/or legal guardian(s) continue to be 
unreachable, the participant will be considered to have withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the maternal participant’s routine clinical 
management and obtained before signing of the ICD may be utilized for baseline 
purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA and protocol.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
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circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
8.1. Efficacy Assessments
8.1.1. Efficacy Assessments – Infant Participants
MA-RTIs in the infant participant will be identified from birth until the end of the infant’s 
participation in the study.  If the infant participant meets any RTI criteria listed below that 
require a visit by or a visit to a healthcare provider (outpatient or inpatient visit, emergency 
room, urgent care, or scheduled home visit), an RTI study visit by the study staff will be 
required (see Section 8.11.7).
The RTI criteria are if the infant experiences 1 or more of the following respiratory signs or 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any duration

Cough

Inability to feed for any duration due to respiratory symptoms

Apnea

Any other respiratory symptom of concern 
Evaluation of these MA-RTI events will be based on predefined clinical signs and symptoms 
and testing criteria (shown in Table 1) obtained at the medically attended visit with the 
healthcare provider and/or the study visit. These events will be assessed and confirmed to be 
contributing to the study endpoints by an independent EAC as per the protocol.
8.1.1.1. Midturbinate Nasal Swab Collection and Testing Requirements for Endpoint 
Confirmation – Infant Participants
Midturbinate nasal swabs will be collected for RSV analyses from infant participants at each 
RTI study visit during the RSV surveillance period from birth until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). The swabs
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will be sent to Pfizer for centralized reverse transcription–polymerase chain reaction 
(RT-PCR) testing.
RSV testing performed locally as part of routine care will be considered valid when analyzed 
under the following conditions:  

Nucleic acid amplification technology (NAAT)-based test result positive for RSV was 
obtained using a Food and Drug Administration (FDA)-cleared assay.
AND

NAAT-based test result was obtained in a laboratory that is currently Clinical Laboratory 
Improvement Amendments (CLIA)-certified or has the equivalent US 
certification/accreditation (eg, College of American Pathologists [CAP]) or the equivalent 
ex-US certification as outlined in the adjudication charter. 
Note: Rapid antigen-based test results will not be considered for endpoint assessment.
Study samples should be collected as close to the medical visit as possible and preferably 
within 72 hours of the MA-RTI visit. Study samples positive for RSV by RT-PCR as 
defined above will count toward the endpoint definition when collected for up to 10 days 
after the MA-RTI, where Day 1 is the day of the MA-RTI visit. These results will be used 
for MA-RTI endpoint definition and confirmation as detailed in Table 1.
8.1.1.2. Events for Adjudication and Submission Guidance – Infant Participants
To maintain scientific integrity, this protocol will use an EAC for the adjudication of all 
efficacy endpoints as summarized below.  The EAC will remain blinded to the maternal 
participants’ vaccine assignments, and the EAC’s assessment of these events will represent 
the final confirmed endpoint classification of the event. 
The efficacy-related events for adjudication include all MA-RTI events. The study 
definitions for endpoint events and the MA-RTI adjudication criteria for the EAC, including 
roles and responsibilities, are specified in the endpoint adjudication committee charter 
(EACC). 
The identification of an MA-RTI will be made by the investigational site and communicated 
to Pfizer or its designee. However, these MA-RTI events may also be identified by Pfizer or 
its designee during the review of clinical data listings or by site monitors during routine 
monitoring of the infant participants’ study records. Pfizer or its designee will notify the 
investigational site of any events identified during this process.
The EAC is responsible for adjudicating whether MA-RTI events fulfill the protocol-defined 
clinical criteria as a primary endpoint, whether the event was due to RSV based on 
confirmatory testing, and the severity of the illness (eg, MA-RTI, MA-LRTI, or severe 
MA-LRTI).  The EAC will adjudicate all RSV-positive MA-RTI cases through the active 
follow-up period including all cases occurring up to 180 days after birth. The EAC will 
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adjudicate severe manifestations of RSV: all RSV-associated cases of hospitalization and 
severe MA-LRTI. All deaths during the study are to be reported to Pfizer Safety upon 
awareness. 
The Pfizer study team or designee will provide a listing of specific documents needed to 
support endpoint adjudication by the EAC. These documents will be detailed in the EACC
and the ISF.  Obtaining and submitting the documentation, including results of local testing 
for RSV, will be the responsibility of the investigational site. Documentation will vary based 
on the potential endpoint requiring adjudication and may include (but not be limited to) 
emergency room visit records, hospital discharge summaries, clinic and/or progress notes, 
diagnostic tests, pathology reports, autopsy reports, and death certificate information, as 
applicable.
Pfizer may request that additional cases of interest be reported to the committee in addition to 
those listed above, including cases in which RSV testing is indeterminant or otherwise 
unclear. Cases that are determined to be RSV positive using non–NAAT-based clinical 
testing can be adjudicated, explored, and summarized descriptively.
8.1.2. Exploratory Efficacy Assessments – Maternal Participants
An MA-RTI will be identified from vaccination until the end of the study and will contribute 
to an exploratory endpoint for maternal participants.  The definition and assessment criteria 
as described in Section 8.10.6 include a visit by or to a healthcare provider (outpatient or 
inpatient visit, emergency room, urgent care, or home visit) for any symptoms in the RTI 
criteria as detailed in Table 2.
The maternal participant should contact the study staff immediately but no later than the next 
scheduled visit to report RTI signs and symptoms for which she sought medical attention. 
The procedures as detailed in Section 1.2.3.1 and Section 8.10.6 will be required to capture 
the event in the CRF.
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal and Infant 
Participants
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition for 
infant participants should not be recorded as AEs. These data will be captured as efficacy 
assessment data only, as these are expected endpoints.  
For maternal participants, MA-RTI events that are consistent with the clinical and endpoint 
definition will be captured as detailed in Section 8.1.2 and will not be recorded as AEs.  
Any SAE that the investigator has judged to have a causal relationship with the 
investigational product MUST be reported to Pfizer Safety as described in Appendix 2, 
even if that event is a component of an endpoint.
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8.1.4. Immunogenicity Assessments 
8.1.4.1. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be approximately 30 mL (~15 mL/visit).  
8.1.4.2. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical 
Consideration for Clinical Trials Performed in Children.31
All infants will have a cord blood sample collected at birth. The cord blood is collected from 
the umbilical cord vein attached to the placenta after the umbilical cord has been clamped 
and cut. Blood should be collected as soon as feasible after birth to minimize coagulation 
and maximize volume. The total volume of cord blood to be collected for antibody 
assessment in this study will be 10 mL. 
If cord blood is unavailable, a blood sample may be collected from the infant participant up 
to 7 days after birth but preferably within 24 hours after birth.  The infant’s weight must 
be used to determine the volume of blood that can be collected (see Table 3).  
A blood sample will be collected from the infant participant only if a cord sample is not
obtained. In the event that a sample is collected, the volume of blood will vary depending on 
the infant’s weight. 
The maximum volume of blood collected from the infant in the absence of cord blood will be 
no more than 5 mL.
Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained
Body Weight (in kg)
Approximate Volume of Blood (in mL) 
to Be Collected 
<1.3
No blood draw
1.3 to ≤2.4
1.0
>2.4 to ≤3.7
2.0
>3.7 to ≤4.9
3.0
>4.9 to ≤6.2
4.0
>6.2
5.0
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant Participants
Maternal sera (prevaccination/time of delivery) and infant cord blood collected will be 
assayed for RSV A and RSV B serum neutralizing titers and anti-RSV prefusion F IgG 
levels. Maternal sera collected may be tested for Ig levels against nonvaccine RSV antigens
to assess natural RSV exposure.
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RSV A and RSV B serum neutralizing titers will be determined and reported as the 
neutralizing titer. IgG levels will be determined against both RSV A and RSV B prefusion F 
antigens in a direct-binding Luminex immunoassay (dLIA) and reported as an anti–
prefusion F IgG level.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development – Maternal and Infant Participants
Samples remaining after completion of the planned assays from blood draws or respiratory 
nasal swab specimens taken throughout the study may be used for additional vaccine and 
infectious disease related research. Samples may also be used for assay development, 
standardization, qualification, and validation.  This work is critical in the development, 
qualification, and validation of serological assays and is required by regulatory authorities for 
their use in the licensure of a vaccine.
8.1.4.5. Respiratory Pathogens – Infant Participants
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI
visit during the RSV surveillance period from birth until Visit 3, and for all hospitalizations 
due to an RTI and severe cases of MA-LRTI during the RTI surveillance period from Visit 
3 until the end of the study (see Section 1.2.4.1 and Table 1). 
Samples will be analyzed for RSV A, RSV B, and other respiratory pathogens by polymerase 
chain reaction (PCR)-based assays at a central laboratory. Additional exploratory analyses 
may also be performed.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.6. Biological Samples – Maternal and Infant Participants
Samples will be used only for scientific research.  Each sample will be labeled with a code so 
that the laboratory personnel testing the samples will not know the maternal or infant
participant’s identity.  Samples that remain after performing assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed. If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No sequencing of the maternal or infant participant’s DNA will be performed. 
The maternal participant may request that her (or her infant’s) samples, if still identifiable, be 
destroyed at any time; however, any data already collected from those samples will still be 
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used for this research.  The biological samples may be shared with other researchers as long 
as confidentiality is maintained, and no testing of the maternal and infant participant’s DNA 
is performed.
8.2. Safety Assessments 
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
Safety parameters will be assessed as described in the SoA and below for both maternal and 
infant participants.
8.2.1. Participant Electronic Diary – Maternal Participants
All maternal participants vaccinated in the study will be observed for at least 30 minutes after 
investigational product administration for any acute reactions. For all maternal participants, 
prespecified local reactions and systemic events will be collected for 7 days after vaccination.  
Maternal participants will be required to use an electronic diary (e-diary), installed on a 
provisioned device or as an application on a personal device, and will be asked to monitor 
and record local reactions, systemic events, and temperature each evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  Prior 
to vaccination, a baseline assessment of prespecified systemic events will be recorded in the 
e-diary.
The e-diary allows recording of these assessments only within a fixed time window each day, 
thus providing the accurate representation of the maternal participant’s experience at that 
time.
Similarly, based on local practice in certain countries/locales, a field worker may visit 
maternal participants in their homes daily after vaccination to assess and record local 
reactions, systemic events, and temperature each day (beginning in the morning) for 6 days 
following vaccination (Day 2 through Day 7, where Day 1 is the day of vaccination).  The 
field worker will be required to record these data on a provisioned device or an application 
on a personal device, thus providing the accurate representation of the maternal participant’s 
experience at that time.  For events persisting at Day 7 and use of antipyretic medication 
continuing at Day 7, the field worker will continue to visit the participant and record 
information until resolution.
Data on local reactions, systemic events, and temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via an internet-based 
portal.  At intervals agreed to by the vendor and Pfizer, these data will be transferred 
electronically to Pfizer for analysis and reporting.  These data do not need to be recorded by 
the investigator in the CRF, except the following conditions:
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
If a maternal participant withdraws because of prompted events recorded in the e-diary, 
the event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF. 
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate maternal participant compliance and as part of the 
ongoing safety review. These prospectively collected occurrences of local reactions and 
systemic events are graded as described in Section 8.2.1.1 and Section 8.2.1.2.
8.2.1.1. Local Reactions – Maternal Participants
Following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), the 
maternal participants/field worker will be asked to assess redness, swelling, and pain at the 
injection site and to record the symptoms in the e-diary or appropriate device, in the evening
or daily based on local practice.
Redness and swelling will be measured by the maternal participant/field worker and recorded 
in measuring device units (range: 1 to 20 and 21+) and then categorized during analysis as 
mild, moderate, or severe based on the grading scale in Table 4. Measuring device units can 
be converted to centimeters according to the following scale: 1 measuring device unit = 
0.5 cm.
A maternal participant with severe redness, swelling, or pain at the injection site will be 
prompted to contact the investigator to perform an unscheduled visit to assess the reaction or 
will be referred to the appropriate healthcare facility at the discretion of the field worker if 
there are any concerns, as appropriate.  In the event that the maternal participant does not 
call, the investigator or qualified designee will contact the maternal participant.
Only an investigator or a qualified designee is able to classify a maternal participant’s local 
reaction as Grade 4, after clinical evaluation of the maternal participant or documentation 
from another medically qualified source (eg, emergency room or hospital record) or, in the 
case of pain at the injection site only, contact with the maternal participant.  If a maternal 
participant experiences a Grade 4 local reaction, the investigator must immediately notify the 
sponsor.  A Grade 4 reaction will be collected as an AE on the CRF.  The event will be 
graded using the AE intensity grading scale (Section 10.2.4).
The site staff/field worker will educate the maternal participant regarding signs and 
symptoms that would prompt site contact.  
If a local reaction persists beyond the end of the e-diary period, the maternal participant will 
be requested to report that information and/or any new AEs that develop to the investigator,
or the field worker will continue to visit the maternal participant to assess and record the 
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information until resolution, as per local practice. The investigator will enter this additional 
information in the maternal participant’s source notes and CRF.
Table 4.
Grading Scale for Local Reactions
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 
20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 
20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis
Pain (at the 
injection site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a maternal participant’s local reaction as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
contact with the maternal participant.  Grade 4 local reactions will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.1.2. Systemic Events – Maternal Participants
Prior to vaccination on Day 1, a baseline assessment of fatigue, headache, vomiting, 
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e-diary. Following 
vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), maternal 
participants will be asked to assess fatigue, headache, vomiting, nausea, diarrhea, muscle 
pain, and joint pain and to record the symptoms in the e-diary in the evening or, based on 
local practice in certain countries/locales, a field worker will visit maternal participants daily 
after vaccination to assess the presence of systemic events each day (beginning in the 
morning) for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination).  The field worker will record the symptoms in the e-diary daily. The symptoms 
will be assessed by the maternal participant according to the grading scale in Table 5.  
Maternal participants will also be instructed to contact site staff if they visit the emergency 
room or are hospitalized for severe fatigue, headache, vomiting, nausea, diarrhea, muscle 
pain, or joint pain within 7 days after vaccination. Based on local practice in certain 
countries/locales, maternal participants will be referred to the appropriate healthcare facility 
at the discretion of the field worker if there are any concerns, as appropriate. In the event 
that the maternal participant does not call, the investigator or qualified designee will contact 
the maternal participant. The study staff/field worker may also contact the maternal 
participant to obtain additional information on events entered into the e-diary.
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Only an investigator or qualified designee is able to classify a maternal participant’s systemic 
event as Grade 4, after clinical evaluation of the maternal participant or documentation from 
another medically qualified source (eg, emergency room or hospital record) or contact with 
the maternal participant.  If a maternal participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.  Grade 4 reactions will be collected as an 
AE on the CRF.  The event will be graded using the AE intensity grading scale 
(Section 10.2.4).
Further, if a systemic event persists beyond the end of the e-diary period, the maternal 
participant will be requested to report that information and/or any new AEs that develop to 
the investigator, or the field worker will continue to visit the maternal participant to assess 
and record the information until resolution, as per local practice. The investigator will enter 
this additional information in the maternal participant’s source notes and CRF.
Table 5.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness in 
diaries)
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Headache
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Vomiting
1 to 2 times in 24 hours
>2 times 
in 24 hours
Requires 
intravenous 
hydration
Emergency room 
visit 
or hospitalization 
for severe 
vomiting
Nausea
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe nausea
Diarrhea
2 to 3 loose stools
in 24 hours
4 to 5 loose stools
in 24 hours
6 or more loose 
stools
in 24 hours
Emergency room 
visit
or hospitalization 
for severe diarrhea
Muscle pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe muscle pain
Joint pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe joint pain
a.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic event as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the maternal participant.  Grade 
4 systemic reactions will be collected on the AE case report form and assessed by the investigator using 
the AE intensity grading scale as detailed in Section 10.2.4.
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8.2.1.3. Temperature – Maternal Participants
A digital thermometer will be given to the maternal participant with instructions on how to 
measure oral temperature at home.  Temperature will be collected in the evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination) and at 
any time during the 7 days following vaccination that fever is suspected. Similarly, based on 
local practice in certain countries/locales, the field worker will visit maternal participants 
daily for 7 days after vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination) to collect the temperature.
Fever is defined as an oral temperature of ≥100.4°F (≥38.0°C). The highest temperature for 
each day will be recorded in the e-diary, where possible. In certain countries/locales, if a 
temperature of ≥100.4°F (≥38.0°C) is recorded for a maternal participant during the 
collection of diary events after vaccination, the field worker will perform a rapid test for 
malaria as per local practice.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature less than 100.4°F [38.0°C]) in order to 
collect a stop date in the CRF. 
A maternal participant with a fever >102.0°F (>38.9°C) will be prompted to contact the 
investigator. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the field worker if there 
are any concerns, as applicable. In the event that the maternal participant does not call, the 
investigator or qualified designee will contact the maternal participant.  The investigator or 
qualified designee will assess the fever and perform an unscheduled visit as appropriate.
Temperature will be measured and recorded to 1 decimal place and then grouped into ranges 
for the analysis according to Table 6.  Temperatures reported in degrees Fahrenheit will be 
programmatically converted to degrees Celsius for reporting.
Table 6.
Ranges for Fever
Fever
≥38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°C
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant Participants
There are no protocol-required laboratory assessments.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
AEs will be reported by the maternal participant/parent(s)/legal guardian(s).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
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meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7). 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
Maternal Participants
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each maternal participant including her fetus begins from the time the maternal 
participant provides informed consent, which is obtained before participation in the study 
(ie, before undergoing any study-related procedure and/or receiving investigational product), 
through and including a minimum of 28 calendar days after the last administration of the 
investigational product.
In this study, the investigator and site staff will ensure the active elicitation and collection of 
safety events as detailed below:

The active collection period for nonserious AEs begins once informed consent has been 
provided and continues through a minimum of 28 calendar days after vaccination.  

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

In addition, AEs occurring up to 48 hours after blood draws that are related to study 
procedures must be reported in the CRF.  

Details of any MA-RTI will not be collected as AEs/SAEs from informed consent until 
the maternal participant completes the study, unless the investigator or an appropriate 
designee deems the event to be possibly related to the investigational product. 
For maternal participants who are screen failures, the active collection period ends when 
screen failure status is determined.
Infant Participants
For the infant participant, the time period for actively eliciting and collecting safety events is 
detailed below:

The active collection period for nonserious AEs begins at birth and continues through and 
including a minimum of 28 calendar days after birth. 

The active collection period for NDCMCs and SAEs begins at birth and continues 
through the last study visit. 
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o
Details of any MA-RTI will not be collected as AEs/SAEs from informed consent 
until the infant participant completes the study, unless the investigator or an 
appropriate designee deems the event to be possibly related to the investigational 
product or if the event resulted in death. See Section 8.1 for the reporting 
procedures for efficacy-related endpoints. Note: Details of the MA-RTI visit 
should be recorded in the eCRF.

In addition, AEs occurring up to 48 hours after blood draws or nasal swabs that are 
related to study procedures must be reported in the CRF.  
For maternal participants, and parent(s)/legal guardian(s) of infant participants born to 
maternal participants, who withdraw from the study and withdraw consent for the collection 
of future information, the active collection period ends when consent is withdrawn. 
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the Vaccine SAE Reporting Form.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy; 
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those that occur within 1 month after birth; or congenital anomaly 
[in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.  In addition, infant deaths after 
1 month of age should be reported as SAEs. 
Further follow-up may be requested by the sponsor and will be handled on a case-by-case 
basis (eg, follow-up on preterm infants to identify developmental delays). 
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety. 
The same is applied for those SAEs after the active collection period has ended, should they 
occur to the fetus.  In addition, infant deaths that occur after 12 months of age should be 
reported as SAEs when the investigator believes the death has at least a reasonable possibility 
of being related to investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
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8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All AEs/SAEs occurring in a participant during the active collection period are recorded in 
the CRF.
The investigator obtains general information on the pregnancy and its outcome for all study 
participants.  The investigator will follow the pregnancy until completion (or until pregnancy 
termination).  In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth.  In the event of a termination, the reason(s) for termination should be 
specified and, if clinically possible, the structural integrity of the terminated fetus should be 
assessed by gross visual inspection (unless preprocedure test findings are conclusive for a 
congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, stillbirth, neonatal death,
defined as those deaths that occur within 1 month after birth; or congenital anomaly [in a 
live-born baby, a stillbirth, or a neonatal death]), the investigator should record this 
information in the CRF.  In addition, infant deaths after 1 month of age should be recorded in 
the CRF as SAEs. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.4).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 2.
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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
Potential efficacy endpoints on this study as defined in Section 8.1 will be excluded from the 
standard SAE reporting process unless deemed possibly related to investigational product.
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the 
Investigational Product
8.3.5.1. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Scenarios of exposure during breastfeeding for infants not delivered during the study must be 
reported, irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours 
of the investigator’s awareness, using the Vaccine SAE Reporting Form.  An 
exposure-during-breastfeeding report is not created when a Pfizer drug specifically approved 
for use in breastfeeding women (eg, vitamins) is administered in accord with authorized use.  
However, if the infant experiences an SAE associated with such a drug’s administration, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.2. Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
investigational product, which may or may not lead to the occurrence of an AE. 
Note: This does NOT apply to maternal participants enrolled in this trial.
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In addition, the scenarios below describe environmental exposures that could lead to an 
exposure during pregnancy (EDP): 

A female becomes or is found to be pregnant, having been exposed (eg, because of 
environmental exposure) to the investigational product; or the female becomes or is 
found to be pregnant after being exposed to the investigational product;

A male has been exposed (eg, because of environmental exposure) to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy. 
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the Vaccine SAE Reporting Form and the Exposure During Pregnancy 
Supplemental Form, as applicable, regardless of whether there is an associated SAE.  In the 
event of an EDP, the information submitted should include the anticipated date of delivery.  
Since the information does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the ISF.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
are as follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.
8.3.6. Adverse Events of Special Interest
This section provides information on adverse events of special interest (AESIs) that may be 
detected during the study.
For infant participants:

Preterm birth (born at <37 weeks’ gestation)
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
Birth weight 1001 to 2500 g

Developmental delay
The following AESIs are to be reported as SAEs:

Extremely preterm birth (<28 weeks)

Extremely low birth weight (≤1000 g)
For maternal participants:

Preterm delivery with cause, if available
All AESIs must be reported as an AE or SAE following the procedures described in
Section 8.3.1 through Section 8.3.4. An AESI is to be recorded as an AE or SAE on the 
CRF. In addition, an AESI that is also an SAE must be reported using the Vaccine SAE 
Reporting Form.
8.3.7. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 4.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 2 of the protocol.
8.3.7.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 4.
8.3.7.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  Follow-up applies to all participants, including 
those who discontinue study intervention.
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The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.7.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
Information will be provided to the sponsor as described in the IP manual. 
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.7.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
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8.3.8. Medication Errors 
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.  
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration by an incorrect route;

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
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8.4. Treatment of Overdose
For this study, any additional dose of investigational product will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose in the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
No interruptions or dose modifications will be made in this study. 
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Health Economics
Health economics will be evaluated in exploratory analyses assessing vaccine impact on 
healthcare resource utilization parameters evaluated during study visits, which may include 
the following: number and type of medical visits, length of hospital stay, requirement for 
mechanical ventilation, requirement for respiratory diagnostic procedures, requirement for IV 
fluids, requirement for prescriptions, and antibiotic use. 
8.10. Procedures – Maternal Participants 
8.10.1. Screening and Vaccination Visit (Clinic; Day -28 to Day 1 – Visit 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant. Each signature on the 
ICD must be personally dated by the signatory.
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Maternal participants who might be illiterate must thumbprint the ICD and it must be signed 
and dated by an impartial witness who was present throughout the entire informed consent 
process before performing any study-related procedures.
The investigator or his or her designee will also sign and date the ICD.  A copy of the 
signed/thumbprinted and dated ICD must be given to the maternal participant.  The source 
data must reflect that the informed consent was obtained before participation in the 
study.
If the maternal participant is found ineligible for the study based on a full assessment of 
inclusion and exclusion criteria, the investigator may advise the participant, either by
telephone or face to face, that the participant will be excluded from further participation in 
the study, as defined in Section 5.4.  All eligible maternal participants will proceed to 
complete the vaccination visit.
Standard-of-care procedures performed prior to informed consent can be considered for use 
in the study provided they are performed in close proximity (approximately up to 28 days) to 
the timing of vaccination and follow guidance around the timing of procedures stipulated in 
the protocol.
In countries/locales where procedures to confirm maternal participant eligibility for
this clinical trial are not routinely performed, the procedures must be obtained and 
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.
The following procedures will be performed:

Obtain written informed consent from the maternal participant before performing any 
study-specific procedures. If the maternal participant is illiterate, she must thumbprint 
the ICD and it must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity).  The date of birth will be 
collected to critically evaluate the immune response and safety profile by age.

Obtain and record current alcohol, tobacco, marijuana, or any illicit drug usage.

Obtain and record any medical, surgical, and obstetric history of clinical significance 
including history from prior and current pregnancy(ies).  

Record the LMP and estimated delivery date (EDD).
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
Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.

Record the prepregnancy BMI in the source documentation. If the prepregnancy BMI is 
not available, record the BMI at the time of the first obstetric visit during the current 
pregnancy. 

Perform targeted physical examination evaluating/noting any clinically significant 
abnormalities within the following body systems: general appearance; skin; head, eyes, 
ears, nose, and throat; heart; lungs; abdomen; musculoskeletal; extremities; neurological; 
and lymph nodes.  Significant medical and surgical history and abnormal observations 
from the physical examination will be documented and recorded in the CRF. 

Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement.
o
Where an obstetric ultrasound examination is not performed at ≥18 weeks of 
pregnancy as part of prenatal standard of care, perform an ultrasound examination.
o
Note: Physical or obstetric examinations performed as standard of care may be 
admissible if performed within 7 days prior to the vaccination visit.

Obtain details of any Ig (including monoclonal antibodies or immune globulin [Rho(D) 
immune globulin, eg, RhoGAM]) or blood products (eg, whole blood, packed cells) given 
at any time during the current pregnancy.

Obtain details of any nonstudy vaccinations given at any time during the current 
pregnancy.

Obtain details of syphilis, HIV, and HBV status.  

Note: Only participants with a documented negative syphilis test result and negative 
HIV antibody and HBV surface antigen test results obtained during the current 
pregnancy are eligible for randomization. 

If not performed as standard of care, assessment should be performed as part of the 
study, locally, and vaccination of maternal participant should be deferred until the 
results are available and confirmed to be negative within 28 days prior to study 
randomization. 

Ensure and document that all the inclusion criteria and none of the exclusion 
criteria are met.

Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.2.3.

Issue the maternal participant an e-diary and provide instructions on its completion.
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
Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures, and provide instructions on their use.

Obtain and record baseline assessment of systemic events prior to vaccination in the 
maternal participant’s source documents. Ask the maternal participant to capture the 
corresponding baseline systemic event measurements in her e-diary.

Prior to vaccination, collect a blood sample of approximately 15 mL for serologic 
assessments (prevaccination blood collection should take place on the same day or within 
7 days before the vaccination visit).

Obtain the maternal participant’s randomization number and investigational product kit 
number using the IRT system. Refer to the IRT manual for further instructions on this 
process.  

Qualified site staff member(s) will administer a single-vial dose of investigational 
product into the deltoid muscle of the (preferably) nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
Please refer to the IP manual for further instruction on this procedure.

Site staff must observe the maternal participant for any acute reactions for at least 
30 minutes after investigational product administration.  

Record any acute reactions in the maternal participant’s source documents, on the AE 
page of the CRF, and on the Vaccine SAE Reporting Form as applicable.

Ask the maternal participant to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination, OR explain to the maternal participant that a field worker 
will visit her every day from Day 2 to Day 7 after vaccination (where Day 1 is the day of 
vaccination) to take her temperature and record systemic events, acute local reactions, 
and use of antipyretic medication in a diary (if applicable).

Ask the maternal participant to contact the site staff or investigator immediately if she 
experiences any of the following from Day 1 to Day 7 after vaccination to determine if an 
unscheduled reactogenicity visit is required as detailed in Section 8.10.5 OR inform the 
maternal participant that if she experiences any of the following from Day 1 to Day 7 
after vaccination or is taking antipyretic medication at Day 7, then the field worker will 
continue to visit until resolution.  Furthermore, the maternal participant will be referred to 
the appropriate healthcare facility at the discretion of a field worker if there are any 
concerns as detailed in Section 8.10.5.

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring >20 measuring device units 
(greater than 10 cm).
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
Severe pain at the injection site.

Any severe systemic event.

Inform the maternal participants that if a temperature of ≥100.4°F (≥38.0°C) is recorded 
during the collection of diary data, she will be required to have a rapid test for malaria as 
per local practice and details will be recorded in the diary (if applicable, based on local 
practice).

Remind maternal participants that study staff may contact them to obtain additional 
information on events entered into the e-diary.

Remind maternal participants to inform the study staff of any AEs and SAEs that occur 
for the duration of the trial as described in Section 8.2 and Section 10.2.

Remind the maternal participant to bring the completed e-diary to the next visit
(if applicable). 

Complete the source documents.

The investigator or an authorized designee completes the CRFs and the blinded 
dispenser/administrator completes the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.  

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6. 

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit (The field worker will contact the maternal participant prior to the next 
study visit to remind her, if applicable).
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8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After Vaccination) 
If delivery occurs before this visit, this visit will not be conducted.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

Review the participant’s e-diary data. Collect stop dates of any e-diary events ongoing 
on the last day that the e-diary was completed and record stop dates in the CRF.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2. Note: Active 
elicitation and collection of AEs and SAEs through 28 days after vaccination must occur 
even if delivery occurs within 28 days after vaccination.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6. 

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit (The field worker will contact the maternal participant prior to the next 
study visit to remind her, if applicable).
8.10.3. Delivery (Maternity Unit)
The delivery visit spans the time from when a participant is admitted in labor through 
discharge following delivery of her infant. Protocol-specified procedures associated with 
this delivery visit may be done at any time during this period.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.
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
If available, record the maternal participant’s group B streptococcal (GBS) status and if 
any medication was given for intrapartum antibiotic prophylaxis (IAP).

Record details of any nonstudy vaccinations given since the last visit.

Collect a blood sample of approximately 15 mL for serologic assessments.  Note:  The 
maternal participant’s blood sample can be taken at any time during the delivery visit, 
preferably before delivery. In the event that the blood sample cannot be obtained 
before delivery, the sample should be collected as close to delivery as possible and at 
most 48 hours postpartum.
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments 
must also be collected.  Cord blood is collected from the umbilical cord vein attached to 
the placenta prior to the blood clotting within the cord and after the umbilical cord has 
been clamped and cut.  This sample should be labeled with the infant’s participant ID 
number.

Record pregnancy outcome information, including vital status of the infant (live, 
stillbirth, or termination), mode of delivery (vaginal delivery, cesarean section, etc), and 
the use of any assisted devices (forceps or vacuum).  

Record details of any MA-RTI, including the diagnosis. 

Record AEs as described in Section 8.2 and Section 10.2.

Ask the maternal participants to contact the site to report any significant illness (new or 
worsening), any medically attended respiratory events (eg, doctor’s visit, emergency 
room visit), or any hospitalization that occurs during the study period as detailed in 
Section 8.10.6.

Ask the maternal participant to contact the site staff or investigator if her newborn infant 
meets the MA-RTI study criteria OR the field worker will contact the maternal 
participant/legal guardian(s) weekly to remind them to report any MA-RTI 
(if applicable).

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.10.4. 6-Month-Postdelivery Visit (Clinic or Telephone; 180 to 210 Days After 
Delivery)

Obtain details of any postnatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [eg, HBIG]) or Rho(D) immune globulin [eg, RhoGAM]) or blood 
products (eg, whole blood, packed cells) given since the last visit.

Record details of any nonstudy vaccinations given since the last visit.

Record details of any MA-RTI, including the diagnosis.

Ask the maternal participant to contact the site staff or investigator if her infant meets the 
MA-RTI study criteria OR the field worker will contact the maternal participant/legal 
guardian(s) weekly to remind them to report any MA-RTI, if applicable.

Record AEs as described in Section 8.2 and Section 10.2.

Complete the maternal participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.5. Unscheduled Reactogenicity Visits 
If the maternal participant reports 1 or more of the following, a contact must occur as soon as 
possible between the maternal participant and the investigator, or a medically qualified 
member of the study site staff, to assess if an unscheduled reactogenicity visit is required OR
based on local practice in certain countries/locales, maternal participants will be referred to 
the appropriate healthcare facility at the discretion of the field worker if there are any 
concerns regarding reactogenicity events, including:

redness at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

swelling at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

severe injection site pain on the arm that the investigational product was 
administered, 

fever ≥39.0°C (≥102.1°F).
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The maternal participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or
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
The participant/field worker recorded an incorrect value in the e-diary (confirmation 
of an e-diary data entry error), or

The investigator or appropriate designee determines that the visit is not required.
This contact will be recorded in the maternal participant’s source notes and in the CRF.
Any ongoing reactions must be assessed at the next scheduled visit.
The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure oral temperature.

Measure the participant’s heart rate.

Measure the participant’s blood pressure (seated).

Measure the minimum and maximum diameters of redness (if present) on the arm in 
which the investigational product was administered.

Measure the minimum and maximum diameters of swelling (if present) on the arm in 
which the investigational product was administered.

Assess if necrosis is present at the injection site on the arm in which the investigational 
product was administered.

Assess if any exfoliative dermatitis is present.

Assess any injection site pain on the arm in which the investigational product was 
administered that is present in accordance with the reactogenicity grading scale provided 
in Section 8.2.1.1.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 8.2.1.2.

Ask the participant if she attended an emergency room visit or was hospitalized.

For severe pain at the injection site resulting in an emergency room visit or 
hospitalization, severe systemic events associated with an emergency room visit or 
hospitalization, any necrosis on the arm in which the investigational product was 
administered, or exfoliative dermatitis, the investigator or qualified designee must assess 
these events in accordance with the intensity AE grading scale provided in
Section 8.2.1.1 and Section 8.2.1.2.
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
Record AEs and SAEs as described in Section 8.2 and Section 10.2.

Complete the participant’s source documents.

The investigator or an authorized designee will complete the CRFs.
The study staff/field worker may contact the participant to obtain additional information on 
events entered into the e-diary, as appropriate.
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria – Maternal 
Participants

Starting from Day 1 after vaccination (where Day 1 is the day of vaccination) until the 
end of the study, all maternal participants will be monitored for MA-RTIs as detailed in 
Section 1.2.3.1 and Section 8.1.2. Maternal participants should notify the site and/field 
worker of the occurrence of any MA-RTIs immediately but no later than the next study 
visit. Note: Site contact may be by an electronic method of communication (including 
but not limited to electronic messaging, short message service [SMS], text, email), by 
phone call, or by face-to-face contact.

The definition of maternal RTI includes 1 or more of the following signs and/or 
symptoms:
o
New or increased sore throat
o
New or increased cough
o
New or increased nasal congestion
o
New or increased nasal discharge
o
New or increased wheezing
o
New or increased sputum production
o
New or increased shortness of breath

Record the details of any MA-RTI, including the diagnosis, the medically attended visit 
location (hospital, outpatient visit, emergency room, urgent care, or home visit), duration 
of hospitalization, intensive care unit (ICU) duration if applicable, prescribed medications 
for the MA-RTI, assessments including RSV test result (eg, NAAT, rapid antigen 
detection tests, or any other molecular diagnostic test), if available, and the final 
diagnosis.

Record the details of any nonstudy vaccinations.

Record AEs as described in Section 8.2 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.
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
Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11. Procedures – Infant Participants
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After Birth)

Manually assign a single infant participant identifier using the IRT system (or 
equivalent).

Collect a cord blood sample of approximately 10 mL for immunogenicity assessments.  
Cord blood is collected from the umbilical cord vein attached to the placenta prior to the 
blood clotting within the cord and after the umbilical cord has been clamped and cut.  
This sample should be labeled with the infant’s participant ID number.

If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 24 hours, but up to 7 days after birth.  The volume of blood collected 
will be based on the weight of the infant (refer to Table 3).

Ensure and document that all the infant inclusion criteria and none of the infant exclusion 
criteria are met.

Collect demography (including complete date of birth [ie, dd-Mmm-YYYY], sex, race, 
and ethnicity).  The date of birth will be collected to critically evaluate the immune 
response.

Obtain and record the infant’s length, head circumference, and weight at birth.

Obtain and record the infant’s birth data, including GA and appearance, pulse, 
grimace, activity, and respiration (Apgar) score. 

Obtain and record background factors as described in Section 10.5.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.

Standard-of-care vital signs and examination procedures can be considered for use in 
the study provided they were performed within 48 hours after birth. Note: Please 
reference the physical examination procedures below for details. 

Perform a physical examination, if not performed as part of standard of care, noting 
any clinically significant abnormalities within the following body systems: general 
appearance; skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; back; 
musculoskeletal; extremities; genitourinary; neurological; and lymph nodes.  
Abnormal results must be recorded on source documents as well as the physical 
examination pages of the CRF; only if the abnormal finding is deemed to be clinically 
significant should this be recorded on the AE pages of the CRF. 
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
Record details of any congenital anomalies on the AE page of the CRF, and report 
as an SAE as described in Section 10.2.3.

Record any medication as described in Section 6.5.5.

Obtain details of any Ig (including monoclonal antibodies [eg, Synagis] or immune 
globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given to the 
infant participant since birth.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Review the weekly contact schedule with the parent(s)/legal guardian(s) and collect 
contact information OR remind the parent(s)/legal guardian(s) that a field worker will 
contact them weekly to remind them to report any MA-RTI (if applicable).

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria. An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11.2. Visit 2 – 1-Month Follow-up (Clinic, 28 to 48 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.

Standard-of-care vital signs and examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit. Note: Please 
reference the physical examination procedures below for reporting details. 

Perform an examination, if not performed as part of standard of care, noting any 
clinically significant abnormalities in the site source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.
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
Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee 
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria.  An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every 7 days 
from birth until the 6-month follow-up visit to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The weekly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.7.1 for guidance on reported cases of 
MA-RTIs in infant participants during the first 6 months after birth. 
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic, 180 to 210 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 

Standard-of-care vital signs and examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit. Note: Please 
reference the physical examination procedures below for reporting details. 

Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 
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
Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of MA-
RTIs in infant participants. 

Ask the parent(s)/legal guardian(s) to contact the investigator immediately if any 
significant illness or hospitalization occurs or if the infant meets the MA-RTI visit
criteria.  An RTI study visit, along with a nasal swab collection, must be performed 
for all hospitalizations due to an RTI and severe MA-LRTIs as described in 
Section 1.2.4.1 and Section 8.11.8.
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if
a clinic visit is conducted). 

Standard-of-care vital signs and examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit. Note: Please 
reference the physical examination procedures below for details.

Perform a targeted physical examination, if not performed as part of routine care as 
described above, noting any clinically significant abnormalities in the source documents. 
Newly identified abnormal findings must be recorded on source documents and, if 
considered clinically significant in the judgment of the investigator/examiner, on the AE 
page of the CRF. Only applicable if a clinic visit is conducted.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies. 
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
Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants except for infant participants born during the first year of the study.

The investigator or an authorized designee completes the CRF for infant participants born 
during the first year of the study. Note: An additional 12-month blinded follow-up period 
for longer-term RTI surveillance and safety oversight will be included for these 
participants.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Confirm the understanding of the infant participant’s parent(s)/legal guardian(s) 
regarding site contact for the study, which is approximately every month (28 to 35 days) 
until the end-of-study visit. Ask the parent(s)/legal guardian(s) to contact the 
investigational site/field worker promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.
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8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days After Birth; 
Infant Participants Born During the First Year of the Study Only)

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 742 Days After 
Birth; Infant Participants Born During the First Year of the Study)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if 
a clinic visit is conducted). 

Standard-of-care vital signs and examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit. Note: Please 
reference the physical examination procedures below for reporting details. 

Perform a targeted physical examination, if not performed as part of routine care, noting 
any clinically significant abnormalities in the source documents . Newly identified 
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abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF. 
Only applicable if a clinic visit is conducted.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents. 

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants born during the first year of the study.
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 Months After 
Delivery)

This is an active surveillance period spanning from birth through 6 months after delivery 
(Visit 3).

The sponsor may alter the frequency of the weekly contacts or the duration of 
surveillance for MA-RTI based on RSV surveillance data or other operational factors.
8.11.7.1. RTI Associated With a Medical Visit – Hospital, Home, or Clinic Visit

Contact the infant participant’s parent(s)/legal guardian(s) approximately every week 
(7 to 10 days) from birth until Visit 3 (6-month follow-up visit), to remind the 
parent(s)/legal guardian(s) to contact the investigational site promptly if the infant meets 
the criteria for an RTI-associated medical visit.  The weekly contact may be via the 
e-diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Table 1 regarding clinical signs 
and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an event requiring a visit to a healthcare provider, the site staff 
and/field worker should confirm, based on information provided, whether the event meets 
the criteria for an MA-RTI. Please refer to Table 1 and Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

When an infant MA-RTI criterion is met or confirmed, the site/field worker will obtain 
records from the medically attended visit and record the healthcare information as 
detailed in Appendix 6.
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
When an infant MA-RTI criterion is met or confirmed, the infant participant will be 
seen as soon as possible and within 72 hours (preferable) or up to 10 days for an RTI 
study visit by the investigational site staff or qualified designee. 

The infant participant may be seen either at the time of the MA-RTI, at home or at the 
study site (if discharged), or if the infant participant has been hospitalized or is receiving 
treatment at another medical facility, the site staff/field worker can conduct the RTI study 
visit at those facilities.  
o
If the RTI study visit is not performed within 72 hours of the event, it should still be 
performed, including the collection of nasal swab specimens. 
o
Targeted assessments at an RTI study visit include but are not limited to:
o
Respiratory signs: lower chest wall indrawing.
o
Vital sign assessment: respiratory rate, heart rate, and oxygen saturation by pulse 
oximetry.
o
Nasal swab collection from the infant participant for testing at the central 
laboratory.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site/field worker if the infant’s 
illness worsens, or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for the event as detailed in Section 8.1.
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit Criteria

This is a long-term surveillance procedure for all infant participants from 6 months after 
delivery (Visit 3) until the last study visit.  

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) from Visit 3 (6-month follow-up visit) until the end-of-study visit, to 
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remind the parent(s)/legal guardian(s) to contact the investigational site promptly if the 
infant meets the criteria for an MA-RTI visit.  The monthly contact may be via the e-
diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Section 8.1 regarding clinical signs 
and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an MA-RTI, the site should obtain additional information and 
determine whether the event also meets the study definition of a severe MA-LRTI. 
o
Note: Severe MA-LRTI is defined in Table 1.

The site/field worker will obtain records from the medically attended visit and record the 
healthcare information as detailed in Appendix 6.

When an infant MA-RTI criterion is confirmed and also meets the study definition of 
hospitalization due to an RTI or a severe MA-LRTI, the infant participant will be seen 
as soon as possible and within 72 hours (preferable) or up to 10 days for an RTI study 
visit that includes a nasal swab collection by the investigational site staff/field worker. 
The staff/field worker will obtain the nasal swab within 72 hours (preferable) or up to 
10 days of the event with the infant participant either at home (if discharged) or, if the 
infant participant has been hospitalized or receiving treatment at another medical facility, 
the site staff/field worker will conduct the visit at those facilities.  
o
Note: Nasal swab collection from the infant participant is for testing at the central 
laboratory.

A targeted RTI study visit will be required for all reported cases of hospitalization due to 
an RTI or severe MA-LRTI only, and this includes but is not limited to:
o
Respiratory signs: apnea, lower chest wall indrawing.
o
Vital sign assessment: respiratory rate, heart rate, and oxygen saturation by pulse 
oximetry.

A targeted RTI study visit is not required for an MA-RTI event not meeting the definition 
of hospitalization due to an RTI or severe MA-LRTI.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the MA-RTI event, including emergency room or
hospitalization details with admission and discharge date (if applicable).

Record any medication as described in Section 6.5.5.
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
Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.  Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site if the infant’s illness worsens, 
or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for hospitalizations due to an RTI and 
severe MA-LRTI events only as detailed in Section 8.1.
8.12. Communication and Use of Technology
In a study of this duration that is event-driven, it is vital to ensure that communication 
between the study site and the maternal participant and parent(s)/legal guardian(s) is 
maintained to ensure that endpoint events are not missed.  This study will employ various 
methods, tailored to the individual participant (maternal and/or infant participant), to ensure 
that communication is maintained and study information can be transmitted securely.  Using 
appropriate technology, a communication pathway between the maternal participant and 
parent(s)/legal guardian(s) and the study site staff will be established.  The maternal 
participant and the parent(s)/legal guardian(s) may be able to utilize their own devices to 
access this technology, or use a device provided by the sponsor.  Traditional methods of 
telephone communication will also be available. The technology solution may facilitate the 
following:

Contact with the investigator.

The ability of the maternal participant/parent(s)/legal guardian(s) to report MA-RTI visits
associated with the infant participant.

An alert in the event that the maternal or infant participant is hospitalized.

Visit reminders.

Messages of thanks and encouragement from the study team.

A platform for recording local reactions and systemic events (e-diary).
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9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Estimands and Statistical Hypotheses
The null hypothesis to be tested concerns VE for the primary endpoints. The RSV vaccine 
will be compared to placebo, testing the hypotheses H0: VE ≤20% vs Ha: VE 20%. For all 
secondary efficacy endpoints, the RSV vaccine will be compared to placebo, testing the 
hypotheses H0: VE ≤0% vs Ha: VE >0%. Hypothesis testing of the secondary endpoints is 
conditional upon rejection of the null hypothesis for at least 1 of the primary endpoints.
9.1.1. Estimands – Infant Participants
9.1.1.1. Efficacy
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with key protocol criteria (evaluable participants): 

VE, defined as the percentage relative risk reduction in the incidence of MA-LRTI due to 
RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of severe MA-LRTI 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of hospitalization 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of all-cause 
MA-LRTI in the RSV vaccine group, relative to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  For participants who 
discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.2. Immunogenicity
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with the key protocol criteria (evaluable participants):

Functional antibody levels estimated by the GMT for RSV A and RSV B serum
neutralizing titers.
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
Geometric mean ratio (GMR), estimated by the ratio of the GMTs for RSV A and RSV B
serum neutralizing titers of the RSV vaccine group to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as missing completely at random (MCAR) is assumed.  For participants 
who discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.3. Safety
In infant participants born to the maternal participants receiving 1 dose of investigational 
product:

The percentage of infant participants with specific birth outcomes.  

The percentage of infant participants having AEs from birth through 1 month of age.

The percentage of infant participants having SAEs, NDCMCs, and new diagnosed 
congenital anomalies from birth through the last study visit.
Missing AE dates and missing AE intensity will be handled according to Pfizer safety rules.
9.1.2. Estimands – Maternal Participants
9.1.2.1. Immunogenicity
In maternal participants receiving 1 dose of investigational product and in compliance with 
the key protocol criteria (evaluable participants):

The immune response, estimated by the GMT for RSV A and RSV B 50% serum 
neutralizing titers.

The immune response, estimated by the GMFR from baseline in RSV A and RSV B 50% 
serum neutralizing titers.

GMR, estimated by the ratio of the GMTs for RSV A and RSV B 50% serum 
neutralizing titers of the RSV vaccine group to the placebo group.

Geometric mean of the IgG levels against RSV prefusion F.

Geometric mean of the Ig levels to nonvaccine RSV antigens.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as MCAR is assumed.  For participants who discontinue from the study 
or have major protocol violations, all postdiscontinuation or postviolation observations will 
be censored.
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9.1.2.2. Safety
In maternal participants receiving 1 dose of investigational product:

The percentage of maternal participants reporting AEs through 1 month after vaccination.

The percentage of maternal participants reporting obstetric complications and SAEs 
through the end of the study.

The percentage of maternal participants reporting local reactions within 7 days of 
vaccination.

The percentage of maternal participants reporting systemic events within 7 days of 
vaccination.
Missing e-diary data will not be imputed; missing AE dates and missing AE intensity will be 
handled according to Pfizer safety rules.
9.2. Sample Size Determination
This is a case-driven study. Sample size is determined as the number of participants to be 
randomized that is expected to accrue the required number of primary endpoint cases in the 
evaluable population. In this study there are 2 primary endpoints, and success on either 
primary endpoint is sufficient (see Section 9.1); power for the study overall is therefore at 
least as high as the power for either primary endpoint individually. In order for the study to 
have at least 90% power to reject the null hypothesis for MA-LRTI due to RSV when true 
VE is 60%, a total of 124 cases of MA-LRTI due to RSV within 90 days of birth are required 
in the evaluable population. This also accounts for potential use of an alpha of 1.25% 
1-sided within the Hochberg multiplicity adjustment. There is no explicit case target for the 
endpoint of severe MA-LRTI due to RSV; depending on the assumed true VE, power for that 
individual hypothesis may be lower, but the power for the primary endpoint family will be at 
least 90%. Hypotheses about VE may be restated as hypotheses about the proportion of 
cases in the RSV vaccine group, conditional upon a fixed total number of cases. If this 
proportion is p, the null hypothesis H0: VE ≤20% is equivalent to H0: p ≥0.444; the 
assumption of VE = 60% corresponds to p = 0.286. Power was evaluated by the exact 
binomial test, and the case target established as that number k for which power is guaranteed 
to be at least 90%, for all k* ≥k. The calculation accounted for the study design 
(1:1 randomization of participants to RSV vaccine : placebo), a single planned interim 
analysis of efficacy (see Section 9.5), and an overall type 1 error of 2.5% 1-sided across the 
2 primary endpoints. 
This global study is planned to be conducted in the United States and other high-income 
countries as well as LMICs. Incidence rates of the primary endpoints are expected to vary in 
different regions. Based on a recently completed Phase 3 trial of an RSV vaccine, the 
assumed incidence rate for MA-LRTI due to RSV through 90 days in low-incidence 
countries, such as the United States, is approximately 1.75%; and in other regions,
approximately 3.90%. With these assumptions, and also allowing for 60% VE and 10% of 
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enrolled participants being nonevaluable, enrollment of approximately 6900 participants is 
planned for the study as a whole. The exact number of participants required to accrue the 
case target may be higher or lower than this, depending on incidence rates, observed VE, and 
the proportion of participants evaluable.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined for infant and maternal 
participants:
Population
Description
Enrolled 
All maternal participants who sign the ICD.
Randomly assigned to 
investigational product
All maternal participants who are assigned a randomization 
number in the IRT system.
Evaluable efficacy –
infant (per-protocol)
All infant participants who are eligible, are born to the 
maternal participants who received the investigational product 
to which they were randomized at least 14 days prior to 
delivery, have valid and determinate results for the proposed 
analysis, and have no major protocol violations. 
Modified intent-to-treat 
(mITT) efficacy – infant
All infant participants who are born to vaccinated maternal 
participants and have valid and determinate results for the 
proposed analysis.
Evaluable 
immunogenicity – infant
All infant participants who are eligible, are born to the 
maternal participants who received the investigational product 
to which they were randomized, have blood drawn for assay 
testing within the specified time frame, have valid and 
determinate assay results for the proposed analysis, and have 
no major protocol violations. 
Evaluable 
immunogenicity –
maternal
All maternal participants who are eligible, receive the 
investigational product to which they were randomized, have 
blood drawn for assay testing within the specified time frame, 
have valid and determinate assay results for the proposed 
analysis, and have no major protocol violations. 
mITT immunogenicity –
infant
All infant participants who are born to vaccinated maternal 
participants and have at least 1 valid and determinate assay 
result for the proposed analysis.
mITT immunogenicity –
maternal
All randomized maternal participants who receive 
investigational product and have at least 1 valid and 
determinate assay result for the proposed analysis. 
Safety – infant
All infant participants who are born to vaccinated maternal 
participants.
Safety – maternal
All randomized maternal participants who receive 
investigational product.  
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9.4. Statistical Analyses 
The SAP will be developed and finalized before database lock for the first planned analysis 
and will describe the participant populations to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data.  This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The analysis of efficacy will use a conditional exact test based on the 
binomial distribution of the number of disease cases in the RSV vaccine 
group, given the total number of cases in both groups. The incidence of 
MA-LRTI due to RSV and severe MA-LRTI due to RSV in infant 
participants will be evaluated in both groups up to 90 days, 120 days, 
150 days, and 180 days after birth.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population. 

The 2 primary endpoints of MA-LRTI due to RSV and severe 
MA-LRTI due to RSV will be tested in parallel using a Hochberg 
multiplicity adjustment procedure. Success of the trial requires 
rejection of the null hypothesis (ie, a CI lower bound >20%) for either 
one of the 2 primary endpoints.

The primary endpoint of severe MA-LRTI due to RSV may be demoted 
to a secondary endpoint, if there are insufficient cases for an adequately 
powered analysis. During the trial, blinded accrual of cases will be 
monitored and prior to any unblinding, a decision rule for this change 
will be established based on the total number of cases of severe 
MA-LRTI due to RSV. 

Testing of the 2 primary endpoints across the time intervals will follow 
a fixed sequence with a gatekeeping strategy. First, the hypothesis 
pertaining to the incidence of the 2 primary endpoints within 90 days 
after birth will be tested, at the full multiplicity-adjusted alpha level, 
using a Hochberg adjustment. If that null hypothesis cannot be rejected, 
testing ends. Otherwise, testing proceeds to the incidence within 120 
days after birth, at the full alpha level. Only primary endpoint(s) that
are successful at all earlier time intervals will be considered at 
subsequent intervals. Testing will proceed to the endpoints evaluated at 
150 days and 180 days, conditional on rejection of the null hypotheses 
for all earlier time intervals. 
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Endpoint
Statistical Analysis Methods

There may be a single interim analysis of the MA-LRTI-due-to-RSV
endpoint when there is an adequate number of cases (at least half the 
target number within 90 days). Based on the fraction of cases included 
in the interim analysis, an alpha level will be derived based on a
Lan-DeMets implementation of the O’Brien-Fleming alpha spending 
function. For example, if there is a single interim analysis at exactly 
50% of the cases, the appropriate 1-sided significance levels are 0.0014 
at the interim analysis and 0.0245 at the final analysis. Implementation 
of these 
1-sided significance levels ensures the overall type 1 error for the 
primary endpoint will be no more than 0.025. See Section 9.5 for more 
details.

At the interim analysis there will also be an assessment for futility, 
based on conditional power for the MA-LRTI-due-to-RSV endpoint. If 
the probability of success at the end of the trial is low, given the interim 
analysis results and the initially assumed VE is applied to the remaining 
data, consideration will be given to stopping the study for futility.

CIs for VE will be calculated using the appropriate multiplicity-adjusted 
alpha level α. If the lower 100(1 - α)% confidence limit for VE exceeds 
20%, the null hypothesis for that endpoint will be rejected.

At the end of the trial, the RSV vaccine may be deemed efficacious if 
there are 43 or fewer cases of MA-LRTI due to RSV in the RSV 
vaccine group out of the 124 total primary endpoint cases.  This 
corresponds to estimated VE = 47% with 95.1% CI = (22%, 64%). For 
severe MA-LRTI, assuming a total of 50 cases occur, the vaccine may 
be deemed efficacious if there are 14 or fewer cases in the RSV vaccine 
group.  This corresponds to estimated VE = 61% with 95.1% 
CI = (26%, 81%). For both of these examples, it is assumed a 1-sided 
alpha of 0.0245 applies to the endpoint in question. A smaller 
multiplicity-adjusted alpha may apply, leading to a higher VE required 
for success. 

Kaplan-Meier curves showing accrual of primary endpoint cases over 
180 days will be presented.
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Endpoint
Statistical Analysis Methods
Secondary

The analysis of secondary efficacy endpoints will use the exact 
conditional binomial method, as for the primary endpoint. Secondary 
endpoints will be examined at the final analysis only. VE will be 
estimated along with 2-sided 95% CI. 

Inference for the secondary endpoints will be conditional upon 
demonstrating success for the primary efficacy endpoint. The 
secondary endpoints of hospitalizations due to RSV and all-cause 
MA-LRTI will be tested in parallel so as to preserve the overall type 1 
error across primary and secondary endpoint families at no more than 
2.5% 1-sided. Multiplicity correction strategies will be defined in the 
SAP. VE for each secondary endpoint will be evaluated sequentially at 
90 days, 120 days, 150 days, and 180 days, as for the primary endpoint. 
Testing will only proceed to later time points conditional on success of 
all previous time points. 

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.
Exploratory

The incidence in infant participants of MA-RTIs due to RSV with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized.

The incidence in infant participants of MA-RTIs due to any cause with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized. All MA-RTIs and severe MA-LRTIs will be summarized 
separately.

The incidence in infant participants of MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The incidence in infant participants of severe MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The incidence in infant participants of hospitalization due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The primary endpoint through 180 days after birth will be summarized 
separately as cases associated with RSV subgroup A or RSV subgroup 
B infection.
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Endpoint
Statistical Analysis Methods

The primary endpoint through 180 days after birth will be summarized 
by interval from vaccination to delivery and by GA at the time of 
vaccination.

The incidence of MA-RTI due to any cause in maternal participants 
from vaccination through 180 days after delivery will be summarized. 
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting 
each event for each vaccine group.

A 3-tier approach will be used to summarize AEs. For both Tier 1 and 
Tier 2 events, the 95% CIs for the difference in the percentage of 
participants reporting the events between the RSV vaccine group and the 
placebo group will be calculated using the test statistic proposed by 
Miettinen and Nurminen; in addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in the percentage of 
participants reporting the events, based on the same test statistic and 
under the assumption that the test statistic is asymptotically normally 
distributed.  A Medical Dictionary for Regulatory Activities (MedDRA) 
preferred term is defined as a Tier 2 event if there are 1% or more 
participants in at least 1 vaccine group reporting the event.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Secondary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting 
each event for each vaccine group.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
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Endpoint
Statistical Analysis Methods
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Exploratory

These analyses will be described in the SAP, finalized before first 
database lock.
9.4.3. Other Analyses 
9.4.3.1. Immunogenicity Analyses
Immunogenicity endpoints are exploratory in the study.  The analyses of immunogenicity 
endpoints will be based on the evaluable populations.  An additional analysis will be 
performed based on the mITT populations if there is enough difference between the mITT 
populations and the evaluable populations.  Immunogenicity data for maternal participants 
and infant participants will be summarized separately, with the exception of maternal-to-
infant placental transfer analysis.  Participants will be summarized according to the vaccine 
group to which they (for maternal participants) or their mothers (for infant participants) were 
randomized.
The secondary and exploratory immunogenicity endpoints will be described by the following 
summaries and the 95% CIs:

GMT of the RSV A and RSV B serum neutralizing titers at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMT of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMFR for RSV A and RSV B serum neutralizing titers from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMFR of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMR of the RSV vaccine group to the placebo group for the RSV A and 
RSV B serum neutralizing titers at each available time point after vaccination (maternal 
participants and infant participants, separately).

GMR of the RSV vaccine group to the placebo group for the combined RSV A/B serum
neutralizing titers at each available time point after vaccination (maternal participants and 
infant participants, separately).
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
Geometric mean of the IgG levels against RSV prefusion F and Ig levels to nonvaccine 
RSV antigens at each available time point by vaccine group (maternal participants and 
infant participants, separately).

Geometric mean of IgG subclass levels (minimally IgG1) against RSV prefusion F at 
each available time point by vaccine group (maternal participants only).
Empirical reverse cumulative distribution curves (RCDCs) for combinations of time points 
and vaccine groups will be presented for RSV A and RSV B serum neutralizing titers.
A sensitivity analysis will be performed to exclude immunogenicity data from mothers and 
their infants following onset of RSV infection between vaccination and delivery (based on 
evidence from the nonvaccine antigen assay). 
Subgroup analyses of the secondary and exploratory immunogenicity endpoints will be 
performed, including an analysis based on GA at the time of vaccination, time from 
vaccination to delivery, and by country subcategories. All subgroup analyses will be defined 
in the SAP.
In addition, the maternal-to-infant placental transfer ratio (infant/mother) of RSV A and 
RSV B serum neutralizing titers and associated 95% CI will be summarized.
9.4.3.2. Healthcare Utilization Analyses
Healthcare utilization endpoints are exploratory in the study; these analyses will be described 
in the SAP and finalized before first database lock. For these analyses, details of healthcare 
resource utilization for all infants will be assessed at each MA-RTI visit from birth through 
the last study visit (730 days after birth). Details of healthcare resource utilization will be 
summarized into a mean/median composite score, which may include the following: number 
and type (eg, respiratory, reactive airway disease [RAD]/asthma/wheezing) of medical visits 
(eg, outpatient, urgent care, emergency room, hospitalization, ICU), length of hospital stay, 
requirement for mechanical ventilation (yes/no, total number of episodes, total number of 
hours/days on treatment), requirement for IV fluids, requirement for respiratory diagnostic 
procedures (eg, chest radiograph, supplemental oxygen, pulse oximetry), requirement for 
prescriptions (eg, total number of prescriptions, selected respiratory medications [eg,
bronchodilators, corticosteroid therapy, racemic epinephrine]), and antibiotic use (eg, total 
number of prescriptions, number of use days).
9.5. Interim Analyses
An interim analysis may be performed to assess efficacy and safety after at least 50% of the 
planned number of cases of MA-LRTI due to RSV have occurred. Because of the relatively 
low number of cases of severe MA-LRTI due to RSV expected, the interim analysis will not 
consider that endpoint. Interim analysis results may be used for internal business decisions 
regarding future study planning, stopping for futility, or stopping for early success.  
The order of cases included in the interim analysis will be determined by the adjudication 
committee as those first confirmed as meeting the protocol-defined criteria. When the target 
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number of cases for the interim analysis is reached, it is possible that additional potential 
cases will be under adjudication. These additional cases will be included in the interim 
analysis only if confirmed as cases by the EAC on the same day that the last per-protocol 
case is confirmed.
The analysis of efficacy will utilize an O’Brien-Fleming alpha spending rule based on the 
fraction of cases of MA-LRTI due to RSV available. For example, to control the overall 
type 1 error for the primary endpoint at 2.5% 1-sided, an interim analysis at 50% of the target 
number of cases would use a 1-sided significance level of 0.14%. The final analysis at the 
target number of cases would use a 1-sided significance level of 2.45%. The alpha levels 
used at interim and final analyses will depend on the exact fraction of cases available at the 
interim analysis.
Testing of the primary endpoints at the interim analysis will follow the sequence of 
interval-specific tests as described in Section 9.4.1.  However, consideration will be given to 
stopping the study for efficacy only if all time intervals through 180 days indicate statistically 
significant efficacy. Secondary endpoints will not be tested at the interim analysis.
Futility will also be assessed using conditional power. Full details will be defined in the SAP. 
For example, if there are 62 cases available for the interim analysis, Table 7 indicates case 
splits for which stopping the study will be considered. The actual number of cases available 
may be slightly higher or lower than 62, and the decision rules amended accordingly.
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals at an 
Interim Analysis
Total Cases
RSV Vaccine 
Group Cases
Placebo Group 
Cases
VE (CI)a
Notes
62
29
33
12% (-49%, 49%)
Conditional power 
<20%b; possible 
futility declaration
62
15
47
68% (24%, 88%)
Maximum number 
of RSV cases 
permitted to 
declare VE >20%
Abbreviation: VE = vaccine efficacy.
a. 99.7% confidence level for efficacy declaration; 95% confidence level for futility.
b. Other conditional power levels may be considered as a trigger for a futility decision.
Before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan, and method of maintaining the study blind as per Pfizer’s standard 
operating procedures (SOPs) will be documented and approved in the DMC charter.  In 
addition, the analysis details must be documented and approved in an interim analysis SAP 
or final SAP.
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9.5.1. Data Monitoring Committee 
This study will use an E-DMC.  Refer to the E-DMC charter for further details.
The E-DMC will review safety data at defined intervals as specified in the charter.  The 
E-DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.
The E-DMC may review unblinded data during closed meeting sessions; however, the 
sponsor will remain blinded and will not be permitted access to the randomization 
assignments until the database is locked and unblinded.
After each meeting, the E-DMC will make recommendations that may include continuing the 
study with or without modification or pausing or stopping vaccination for safety or other 
reasons.
The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints, to regulatory authorities, as appropriate.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and
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of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the maternal 
participant and answer all questions regarding the study.
Maternal participants must be informed that their participation is voluntary.  Maternal 
participants will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability 
and Accountability Act (HIPAA) requirements, where applicable, and the IRB/EC or study 
center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the maternal participant.
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Before any study-specific activity is performed, the investigator, or a person designated by 
the investigator, will obtain written informed consent from each maternal participant.  This 
will include written informed consent for the mother and the fetus during the pregnancy, and 
the infant’s continuation in the study after delivery.  Informed consent will be obtained from 
the father of the fetus/infant if mandated by local requirements.
Participants who are rescreened may be required to sign a new ICD as per IRB, local 
regulations, etc.
If during the study, the investigator determines that the maternal participant is for any reason 
no longer capable of providing informed consent, the infant’s continued participation in the 
study requires consent to be obtained from the parent(s)/legal guardian as determined by 
local regulations, legal requirements, and the IRB/EC. 
Note: For the infant participant, the term parent(s)/legal guardian denotes the “legally 
authorized representative.”
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its SOPs.
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In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (clinical study report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the US Basic 
Results document is posted to www.clinicaltrials.gov.
Documents Within Marketing Authorization Packages/Submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
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24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan/contracts.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
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the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the site Source Data Agreement 
Plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;
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
Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study (or 
study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
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question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
For maternal immunization clinical studies conducted in pregnant women, data on the EDP
including any SAEs/nonserious AEs as well as pregnancy outcomes are collected and 
analyzed in the clinical database. All SAEs are reported to Pfizer Safety using the Vaccine 
SAE Reporting Form. In case of a new pregnancy in a maternal participant before the end of 
the study, any exposure to the investigational product is reportable to Pfizer Safety within 
24 hours of investigator awareness using the Vaccine SAE Reporting Form/EDP 
supplemental form.
The term “participant” in this section refers to (1) the maternal participant and her fetus; and 
after delivery (2) the maternal participant and (3) the infant participant.
10.2.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (eg, cesarean section, endoscopy, appendectomy): the 
condition that leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs)
An NDCMC is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
10.2.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
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serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording safety events on the CRF and 
for reporting safety events on the Vaccine SAE Reporting Form to Pfizer Safety.  These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and (3) 
occupational exposure. 
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
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terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study via 
occupational exposure
None
Occupational exposure 
(regardless of whether 
associated with an AE)  

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE.
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Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING
to describe the maximum intensity of the AE. For purposes of 
consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent 
intervention indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.
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
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused the 
event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible.  This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any anonymized 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
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10.2.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data become 
available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see next 
section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
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10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
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
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with International 
Organization for Standardization (ISO) 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.4.1. Definition of AE and Adverse Device Effect (ADE)
AE and ADE Definition 

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational medical device.  
This definition includes events related to the investigational medical device or 
comparator and events related to the procedures involved except for events in users or 
other persons, which only include events related to investigational devices.

An ADE is defined as an AE related to the use of an investigational medical device.  
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device Effect, and 
Unanticipated Serious Adverse Device Effect
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is an AE that:
a. Led to death. 
b. Led to serious deterioration in the health of the participant, that either resulted in:

A life-threatening illness or injury.  The term “life-threatening” in the definition of 
serious refers to an event in which the participant was at risk of death at the time of 
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the event. It does not refer to an event that hypothetically might have caused death, 
if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
Serious Adverse Device Effect (SADE) Definition

A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE.
Unanticipated Serious Adverse Device Effect (USADE) Definition

A USADE is a serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis management 
file.
10.4.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance.  Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator 
to review all documentation (eg, hospital progress notes, laboratory reports, and 
diagnostic reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information in 
the participant’s medical records, in accordance with the investigator’s normal clinical 
practice and on the appropriate form of the CRF.
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
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of following the reporting process described in the IP 
manual.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
“severe” should not be confused with an SAE. “Severe” is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as “severe.”

An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as “severe.”
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency.
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
A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency and has 
provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE/SAE/Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE/SAE/ device deficiency 
as fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
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10.4.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred 
method to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.4.6. Reporting of SADEs
SADE Reporting to Pfizer Safety 
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.
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10.5. Appendix 5: Background Factors
1. Information on the following will be collected at Visit 1, Visit 4 (12-Month), and 
Visit 6 (24-Month) for all infant participants:

Educational level of parent(s) or legal guardian(s).

Exposure to smoke (including tobacco smoke).

Number of persons in the household ≥18 years of age.

Number of children <18 years of age in the household and if they attend school/ 
daycare.
o
Number of children in the household under 5 years of age (under 60 months).
o
Number of children in the household ≥5 years of age (≥60 months).
2. Information on the following will be collected at each postbirth visit:

Childcare/daycare (for infant participants).

Breastfeeding information (including whether or not breastfeeding is exclusive).
3. Information on the following will be collected at each RTI study visit:

Number of missed days of work for parent(s) or legal guardian(s) due to the infant 
participant’s illness.
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10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria Checklist 
for MA-RTI Visit – Infant Participants
When an infant RTI medical visit criterion is met or confirmed, the site will obtain records 
from the medical visit and capture the healthcare information as detailed below in the eCRF. 
This information is based on respiratory-related assessments including examination findings, 
clinical findings, and any pathogen-related assessments/findings. 
Medical Visit - Visit Details and Assessment Requirements
Note: This should not be linked to a study visit but may overlap with the RTI study visit. 
The following fields and clinical assessment details should be obtained from relevant 
records for the medically attended event prior to each RTI study visit to support the 
assessment of the RTI event.

Reason for visit including date/time, eg,
o
Nasal discharge for 24 hours or more.
o
Difficulty breathing, labored breathing, or rapid breathing for any duration.
o
Cough.
o
Inability to feed for any duration due to respiratory symptoms.
o
Apnea.
o
Any other respiratory symptom of concern.

Location of medical visit (inpatient clinic, outpatient clinic, emergency department, 
urgent care, hospitalization, home visit, other). Note: study visits should NOT be 
recorded here.
o
If hospital visit, was this triggered by an RTI (include details pertaining to duration
as well as admission and discharge information and records)?

Clinical findings pertaining to respiratory symptoms and/or RTI, as detailed below but 
not limited to:
o
Presence or absence of pertinent examination findings, eg, apnea (documented as per 
chart), wheezing, fever, cough, nasal congestion, intercostal retractions, lower chest 
wall indrawing, grunting, crackles, decreased breath sounds, other abnormal breath 
sounds, dry mucous membranes, skin tenting, sunken fontanelle, difficulty feeding,  
wheezing, failure to respond/unconsciousness, etc. 
o
Respiratory rate from highest/worst value of visit.
o
Oxygen saturation (SpO2) from lowest/worst value of visit.
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o
Oxygen supplementation (assisted ventilation, including type of respiratory assistance 
[respirator, “state-of-the-art” occlusive nasal prongs, face tent, etc]).

Days of supplementary oxygen.

Use of nasal cannula.

Use of high-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive).
o
Heart rate from worst value of visit when performed consistently.
o
Additional clinical or respiratory related assessments including chest x-ray 

Local test results for RSV as part of routine clinical care:
o
Testing platform used (clinical list of all platforms and validated by research).
o
Result (list: positive, negative, indeterminate, other).

Record the provider diagnosis, including any causative pathogen (if applicable), eg, RSV 
bronchiolitis, asthma, influenza, etc.

Obtain details of all prescribed medications including IV fluid usage.

Obtain details of all AEs/SAEs in line with study requirements. Note: MA-RTIs are not 
AEs/SAEs.
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10.7. Appendix 7: Country-Specific Appendix – Applicable to Japan Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
10.7.1. Informed Consent for the Maternal Participants 18 to <20 Years Old
Informed consent for maternal participants 18 to <20 years old and their infant participants 
will be obtained based on current Japanese civil code article 753 until 01 April 2022.

Married maternal participants 18 to <20 years of age are deemed to have reached 
“majority” and each maternal participant will sign the ICD for her and her infant’s study 
participation.

Unmarried maternal participants 18 to <20 years of age are deemed “minors.”

When the maternal participant is a minor under local law, the investigator, or a person 
designated by the investigator, will obtain written informed consent from the maternal 
participant’s legally acceptable representative, parent(s), or legal guardian as well as 
the maternal participant’s assent (affirmative agreement) for her and her child’s study 
participation before any study-specific activity is performed. The investigator will 
retain the original of each signed consent and assent document.

The assent form for a minor must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements, including applicable privacy 
laws.

The assent form for a minor used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB before use, and available for 
inspection.

The investigator must ensure that the maternal participant’s legally acceptable 
representative, parent(s), or legal guardian is fully informed about the nature and 
objectives of the study and possible risks associated with participation.

The source documents must record that the maternal participant was a minor at 
the time of signing the ICD, how the investigator determined that the person 
signing the consent was the maternal participant’s legally acceptable 
representative, the consent signer’s relationship to the maternal participant (eg, 
parent), and that the maternal participant’s assent was obtained.

When the minor maternal participants reach the age of majority during the study, as 
recognized under local law, they must reconsent as adults to remain in the study.

Beginning on 01 April 2022, when the amended civil law in which individuals 18 years 
of age and older are deemed to have reached majority is implemented, the investigator, or 
a person designated by the investigator, will obtain written informed consent from the 
maternal participant.
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10.7.2. Temperature Measurement and Definition of Fever

Axillary temperature will be measured at Visit 1 and as required at an unscheduled visit, 
and will be measured by the maternal participants for 7 days following vaccination.

For the maternal participants enrolled in Japan, an axillary temperature of 37.5C meets 
the definition of a current febrile illness in the criteria for temporarily delaying vaccine 
administration described in Section 5.2.3.

For the purpose of recording the temperature in the e-diary, fever is defined as an axillary
temperature of 38.0C (100.4F) for maternal participants enrolled in Japan.
10.7.3. Safety Monitoring in the Sentinel Cohort - Maternal Participants
As Study C3671008 is a first-in-Japanese study and in accordance with a recommendation 
from the Pharmaceuticals and Medical Devices Agency (PMDA), the study will utilize a 
sentinel cohort for the maternal participants enrolled in Japan with progression to study 
enrollment at all study sites after a safety review (data from each maternal participant 
through 14 days after vaccination).  In addition to the study procedures and requirements 
specified in the protocol for Study C3671008, the following procedures will be required for 
the maternal participants enrolled in the sentinel cohort in Japan.
10.7.3.1. Enrollment of Maternal Participants in the Sentinel Cohort
In the sentinel cohort, approximately 8 maternal participants will be enrolled.  No more than 
4 maternal participants per day can be randomized.  Vaccination of the remaining maternal 
participants in the sentinel cohort will commence no sooner than 48 hours after the fourth 
participant received her vaccination.  
10.7.3.2. Conclusion of the Sentinel Cohort
After enrollment in the sentinel cohort is completed, the Pfizer internal review committee 
(IRC) will review at least 14 days of postvaccination safety data from all maternal 
participants enrolled in the sentinel cohort, including all local reactions, systemic events, and 
AEs.  An acceptable review will trigger an expansion of study enrollment to all study sites in 
Japan. Refer to the IRC charter for further details.
10.7.3.3. Additional Visit - Day 15 Follow-up Visit (Clinic or Telephone; 14 to 16 Days 
After Vaccination)
All maternal and infant participants enrolled in this study will follow the protocol for 
Study C3671008.  In addition, the maternal participants enrolled in the sentinel cohort in 
Japan will have a Day 15 follow-up visit conducted either at the study site or via telephone.  
This visit should be conducted 14 to 16 days after vaccination. 

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.
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
Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given since the last visit.

Review the participant’s e-diary data.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6.

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit.
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10.7.3.4. Schedule of Activities for Maternal Participants Enrolled in the Sentinel Cohort in Japan
The following table provides an overview of the protocol visits and procedures for the maternal participants enrolled in the sentinel 
cohort in Japan.  Refer to Section 1.2.3.1 for the Schedule of Activities for the Maternal Participants: RTI Surveillance for Medically 
Attended Respiratory Tract Illness Visits (Vaccination Until the End-of-Study Visit).
Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity Unit
Clinic or Telephone
Informed consent for maternal participant and her 
infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current alcohol, tobacco, marijuana, or any 
illicit drug usage
X
Record vital signs
X
Targeted physical examination performed on the same 
day or within 7 days before the vaccination visit
X
Record details of any antenatal and/or postnatal steroid 
treatment, monoclonal antibodies, blood products, or 
Rho(D) immune globulin
X
X
X
X
X
Record details of the maternal participant’s GBS status 
and if any medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
X
Review eligibility criteria
X
X
X
X
Review temporary delay criteria
X
Prevaccination blood draw for serologic assessment
(~15 mL) on the same day or within 7 days before the 
vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and 
measuring devicef
X
Obtain and record baseline assessment of prespecified 
systemic events prior to vaccination in the e-diary
X
Administer investigational product
X
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Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity Unit
Clinic or Telephone
Postvaccination observation (at least 30 minutes) and 
assessment of immediate AEs
X
Delivery blood draw for serologic assessment (~15 
mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X
X
Record AEs, as appropriateh
X----------------------------------------------------X
Record SAEs, as appropriateh
X
X
X
X
X
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of the schedule 
of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; 
MA-RTI = medically attended respiratory tract illness.
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Visit Description
Screening and 
Vaccinationa
Day 15 Follow-up
1-Month 
Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
14 to 16 Days
After Vaccination
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or 
Telephone
Clinic or 
Telephone
Maternity Unit
Clinic or Telephone
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.    Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound
examination. As part of the obstetric history, details regarding the last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.    AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.    Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and/or the field worker (as per local practice) will record (in an e-diary) a baseline 
assessment of prespecified systemic events prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination (where Day 1 is the 
day of vaccination).  Remind maternal participants that the study staff/field worker may contact them to obtain additional information on events entered 
into the e-diary.  Ask maternal participants to contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 
following vaccination, to determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal participant may be 
referred to the appropriate healthcare facility at the discretion of a field worker if there are any concerns.
g.    Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.    The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  Please see Section 8.3.1 for reporting 
requirements and timelines.
i.    A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product.
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10.8. Appendix 8: Country-Specific Gestational Age Assessment Appendix – Applicable 
to the Gambia and South Africa Only
The following supplementary text should be read in conjunction with the C3671008 protocol:
Participants who have not had ultrasound assessments to determine eligibility during 
routine care should be consented, and have an ultrasound within 90 days prior to 
vaccination in order to comply with inclusion criteria #1 in Section 5.1.1.
Safety endpoints:
The time period and frequency for collecting AE and SAE information by the investigator 
and site staff should follow Appendix 2, with the exception of the additional screening 
window for sites conducting ultrasounds procedures from -90 to -28 days. At these sites, the 
safety reporting periods should be as follows:

AEs occurring up to 48 hours after ultrasound assessment that the investigator 
deems are related to the study procedure must be reported in the CRF.

The active collection period for SAEs begins once informed consent has been 
provided until the maternal participant completes the study.

The active collection period for nonserious AEs begins 28 days prior to 
vaccination and continues through a minimum of 28 calendar days after
vaccination as described in Section 8.3.1 and Section 10.2.
MA-RTI endpoints:
Maternal MA-RTIs are collected from the time of vaccination to the end of the study period 
as described in Section 8.1.2.
Note: For maternal participants who are screen failures, the active collection period ends 
when screen failure status is determined. 
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10.9. Appendix 9: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ADE
adverse device effect
AESI
adverse event of special interest
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
Apgar
appearance, pulse, grimace, activity, and respiration
AST
aspartate aminotransferase
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
Clinical Laboratory Improvement Amendments
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EAC
endpoint adjudication committee
EACC
endpoint adjudication committee charter
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine 
GA
gestational age
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Abbreviation
Term
GBS
group B streptococcal
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBIG
hepatitis B immune globulin
HBV
hepatitis B virus
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IAP
intrapartum antibiotic prophylaxis
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
Ig
immunoglobulin
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ISF
investigator site file
ISO
International Organization for Standardization
IUI
intrauterine insemination
IV
intravenous
IWR
interactive Web-based response
LFT
liver function test
LMIC
lower- and middle-income country
LMP
last menstrual period
LRTI
lower respiratory tract illness
MA-LRTI
medically attended lower respiratory tract illness
MA-RTI
medically attended respiratory tract illness
MCAR
missing completely at random
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NAAT
nucleic acid amplification technology
NDCMC
newly diagnosed chronic medical condition
PCD
primary completion date
PCR
polymerase chain reaction
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Abbreviation
Term
PFS
prefilled syringe
PMDA
Pharmaceuticals and Medical Devices Agency
PT
prothrombin time
RAD
reactive airway disease
RCDC
reverse cumulative distribution curve
RSV
respiratory syncytial virus
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RTI
respiratory tract illness
RT-PCR
reverse transcription–polymerase chain reaction
SAE
serious adverse event
SADE
serious adverse device effect
SAP
statistical analysis plan
SMS
short message service
SoA
schedule of activities
SOP
standard operating procedure 
SpO2
oxygen saturation
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Tdap
tetanus, diphtheria, and acellular pertussis vaccine
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VE
vaccine efficacy
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11. REFERENCES
1
Meissner HC. Respiratory syncytial virus. In: Long SS, Prober CG, Fischer M, eds. 
Principles and practice of pediatric infectious diseases. 5th ed. Philadelphia, PA: 
Elsevier; 2018:1162-5. 
2      Hall CB, Weinberg GA, Blumkin AK, et al. Respiratory syncytial virus–associated 
hospitalizations among children less than 24 months of age. Pediatrics 
2013;132(2):e341-8.
3
Shi T, McAllister DA, O’Brien KL, et al. Global, regional, and national disease burden 
estimates of acute lower respiratory infections due to respiratory syncytial virus in young 
children in 2015: a systematic review and modelling study. Lancet
2017;390(10098):946-58.
4
Scheltema NM, Gentile A, Lucion F, et al. Global respiratory syncytial virus-associated 
mortality in young children (RSV GOLD): a retrospective case series. Lancet Glob
Health 2017;5(10):e984-91.
5
Parikh RC, McLaurin KK, Margulis AV, et al. Chronologic age at hospitalization for 
respiratory syncytial virus among preterm and term infants in the United States. Infect
Dis Ther 2017;6(4):477-86.
6
American Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis 
Guidelines Committee. Policy statement—updated guidance for palivizumab 
prophylaxis among infants and young children at increased risk of hospitalization for 
respiratory syncytial virus infection. Pediatrics 2014;134(2):415-20. 
7
Blanken MO, Rovers MM, Molenaar JM, et al. Respiratory syncytial virus and recurrent 
wheeze in healthy preterm infants. N Engl J Med 2013;368(19):1791-9.
8
Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk 
of wheeze and allergy by age 13 years. Lancet 1999;354(9178):541-5.
9
Weber MW, Mulholland EK, Greenwood BM. Respiratory syncytial virus infection in 
tropical and developing countries. Trop Med Int Health 1998;3(4):268-80.
10
Glezen WP, Taber LH, Frank AL, et al. Risk of primary infection and reinfection with 
respiratory syncytial virus. Am J Dis Child 1986;140(6):543-6.
11
American Academy of Pediatrics. Respiratory syncytial virus. In: Kimberlin DW, Brady 
MT, Jackson MA, Long SS, eds. Red book: 2018 report of the Committee on Infectious 
Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:682-92. 
12
Prescott WA Jr, Doloresco F, Brown J, et al. Cost effectiveness of respiratory syncytial 
virus prophylaxis: a critical and systematic review. Pharmacoeconomics
2010;28(4):279-93.
13
Synagis [prescribing information]. Gaithersburg, MD: MedImmune LLC; 2017.
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14
Munoz FM, Ralston SL, Meissner HC. RSV recommendations unchanged after review 
of new data. AAP News 19 Oct 2017. Available from: 
http://www.aappublications.org/news/2017/10/19/RSV101917. Accessed 15 Nov 2018. 
15
The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus 
monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection 
in high-risk infants. Pediatrics 1998;102(3):531-7.
16
Baker CJ, Carey VJ, Rench MA, et al. Maternal antibody at delivery protects neonates 
from early onset group B streptococcal disease. J Infect Dis 2014;209(5):781-8.
17
Dangor Z, Kwatra G, Izu A, et al. Correlates of protection of serotype-specific capsular 
antibody and invasive group B Streptococcus disease in South African infants. Vaccine
2015;33(48):6793-9.
18
Skoff TH, Blain AE, Watt J, et al. Impact of the US maternal tetanus, diphtheria, and 
acellular pertussis vaccination program on preventing pertussis in infants <2 months of 
age: A case-control evaluation. Clin Infect Dis 2017;65(12):1977-83.
19
Baxter R, Bartlett J, Fireman B, et al. Effectiveness of vaccination during pregnancy to 
prevent infant pertussis. Pediatrics 2017;139(5):e20164091.
20
Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and 
protection of their infants. N Engl J Med 2014;371(10):918-31. 
21
Benowitz I, Esposito DB, Gracey KD, et al. Influenza vaccine given to pregnant women 
reduces hospitalization due to influenza in their infants. Clin Infect Dis
2010;51(12):1355-61.
22
Forbes ML, Kumar VR, Yogev R, et al. Serum palivizumab level is associated with 
decreased severity of respiratory syncytial virus disease in high-risk infants. Hum 
Vaccin Immunother 2014;10(10):2789-94.
23
Schmoele-Thoma B, Falsey AR, Walsh EE, et al. Phase 1/2, first-in-human study of the 
safety, tolerability, and immunogenicity of an RSV prefusion F-based subunit vaccine 
candidate [poster 2755]. Poster presented at IDWeek; 02-06 Oct 2019; Washington, DC.
24
McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer 
bound to a prefusion-specific neutralizing antibody. Science 2013;340(6136):1113-7.
25
Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants 
despite prior administration of antigenic inactivated vaccine. Am J Epidemiol
1969;89(4):422-34. 
26
Graham BS. Biological challenges and technological opportunities for respiratory 
syncytial virus vaccine development. Immunol Rev 2011;239(1):149-66.
27
Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial 
virus purified fusion protein-2 vaccine in pregnant women. Vaccine 2003;21(24):3465-7.
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28    Novavax. Phase 3 and beyond: the RSV F nanoparticle vaccine for infants via maternal 
immunization [slide 26]. Presentation at the World Vaccine Congress; 14-17 Apr 2019; 
Washington, DC. Available from: https://novavax.com/download/files/posters/2019-
World_Vaccine_Congress/2019.04.16-World_Vaccine_Congress.pdf. Accessed: 25 Nov 
2019.
29     Regen AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization 
during pregnancy in 4 high-income countries, 2010–2016.  Clin Infect Dis 
2018;67(12):1915-8. Available from: https://doi.org/10.1093/cid/ciy439. Accessed: 
25 Nov 2019.
30     Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: case definition & guidelines for 
data collection, analysis, and presentation of immunisation safety data. Vaccine. 
2016;34(49):6047-56.
31
European Commission. Ethical considerations for clinical trials on medicinal products 
conducted with minors. 18 Sep 2017. Available from:  
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/2017_09_18_ethical_consid_ct_with_minors.pdf. Accessed 21 Feb 2019.
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Document Approval Record
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PPD
PPD

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671008
Final Protocol Amendment 1, 24 March 2020
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLINDED,
PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND 
SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F 
SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING 
PREGNANCY
Investigational Product Number:
PF-06928316 
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine 
United States (US) Investigational New 
Drug (IND) Number:
017931
European Clinical Trials Database 
(EudraCT) Number:
2019-002943-85
Protocol Number:
C3671008
Phase:
3
Short Title: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants 
Born to Women Vaccinated During Pregnancy.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
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Page 2
Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original protocol
05 December
2019
Not applicable (N/A)
Protocol 
Amendment 1
24 March 2020
PROTOCOL SUMMARY: Clarification text was 
added in various sections of the main body of the 
protocol to match the revisions made to the protocol 
summary.
Throughout: The protocol now contains final 
wording regarding the double-blinded, placebo-
controlled study design and the final dose and 
formulation of the respiratory syncytial virus 
stabilized prefusion F subunit vaccine (RSVpreF). 
This is as a result of the analysis of the safety, 
tolerability, and immunogenicity data from the 
C3671003 maternal Phase 2b trial.
Section 1.2.1 Study Design – Maternal Participants: 
The final dose and formulation of RSVpreF were 
inserted, including the lyophile match for the 
placebo.
Section 1.2.2 Study Design – Infant Participants: 
The text box pertaining to the vaccine group arms 
was deleted. The maternal-infant dyads will be 
randomly assigned in this study. Rationale: Infant 
participants will not be administered the 
investigational product. Therefore, the current 
placement is potentially confusing to readers.
Section 1.2.3 Schedule of Activities for Maternal 
Participants, Section 5.2.3, and Section 8.10.1: 
Clarification text was added as follows:
o
The immunogenicity blood collection and 
physical examination window requirements 
before vaccination were aligned to provide 
greater logistical convenience for the 
investigational sites with respect to enrolling 
participants into the study.
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o
The wording for the study objectives pertaining 
to the request for intrapartum antibiotic 
prophylaxis (IAP) details for maternal 
participants with a group B streptococcal (GBS) 
status was revised to be consistent with the 
study procedural objectives, which are to collect 
GBS status and to ascertain whether any 
medication was given for IAP. This resulted in 
the deletion of the text in Section 6.5.3, as this 
information is captured in Section 8.10.3.
o
A reference to the immunogenicity blood draws 
for maternal participants was added to clarify 
the adverse event (AE) reporting requirements 
for events that might occur as a result of study-
related procedures.
Section 1.2.3.1 Schedule of Activities for Maternal 
Participants – Respiratory Tract Illness (RTI) 
Surveillance for Medically Attended Respiratory 
Tract Illness (MA-RTI) Visits: 
o
Details to be collected during an MA-RTI were 
revised.
o
Clarification was added regarding the safety 
reporting requirements for MA-RTI events that 
might occur during the study. 
Section 1.2.4 Schedule of Activities for Infant 
Participants: 
o
Visit flexibility was increased to prioritize 
participant safety and adherence to local 
guidance in the event of a coronavirus disease 
2019 (COVID-19) outbreak or other outbreaks. 
o
The physical examination and vital sign 
assessment windows for the study were aligned 
to provide greater logistical convenience for the 
investigational sites with respect to compliance 
to study protocol requirements.  
o
The protocol safety reporting criteria and period 
for adverse events (AEs), serious adverse events 
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(SAEs), and newly diagnosed chronic medical 
conditions (NDCMCs) were streamlined.
Section 1.2.4.1 Schedule of Activities for Infant 
Participants: RTI Study Visits During the Study: 
The table was revised, including splitting the 
schedules of activities for unscheduled RTI visits 
for all infant participants into RTI surveillance from 
birth to 6 months and RTI surveillance from 6 
months to the end of the study. The procedures were
streamlined for these RTI study visits to improve 
clarity and consistency.  
Table 1: Clarification has been added as to when a 
study visit is triggered for reported MA-RTI 
endpoint events on the study. Day 1 is the day of the 
MA-RTI visit as detailed in Section 8.11.7.
In addition, clarification has been added as to what 
constitutes the site source for confirmed study 
endpoint criteria, in order to provide the sites 
guidance on what documentation will eventually be 
submitted to the endpoint adjudication committee 
(EAC) for evaluation.
Section 3.1: The exploratory endpoints were revised 
to correspond with the planned statistical analyses 
of RTI events in the pediatric population. This does 
not represent a change to the study design but 
instead better reflects the total statistical analysis 
plan. 
Section 3.1, Section 3.2, and throughout: To 
improve clarity and ensure consistency, the use of 
“RSV-neutralizing antibody titers” has been 
changed to RSV serum neutralizing titers.” This is 
the sponsor’s preference based on what the 
neutralizing activity assay is based upon, and in this 
case, it is whole serum and not just the purified 
antibodies during these immunogenicity 
assessments.  
Section 3.3, Section 8.1.1.2, Section 8.1.3, and 
Section 10.2: For further clarification, the protocol’s 
safety and endpoint reporting requirements were 
amended to ensure consistency with Pfizer’s 
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updated safety reporting requirements for endpoint-
defined studies.
Section 4.3: The text “availability of these data are 
expected in 2020” was removed as this statement 
does not accurately reflect the current decision-
making process for the dose and formulation 
selection activities for this study. 
Section 5.2.1: Clarification text was added to the 
exclusion criterion for body mass index (BMI) and 
congenital anomalies based on study requirements.
Section 5.2.3, Section 6.5.1, and Section 6.5.2: The 
tetanus, diphtheria, and acellular pertussis vaccine 
(Tdap) administration requirements text was 
modified to describe the timing of vaccinations 
based on data from the C3671004 study, once 
available. This change will better reflect clinical 
practice and will facilitate recruitment of suitable 
maternal participants for the study.
Section 6.1.1, Section 6.1.3, Section 8.4, and
Section 8.10.1: Clarification text was added to 
address investigational product reconstitution 
volume and administration requirements. This 
change is to ensure consistency with the 
investigational product administration 
documentation for the study.  
Section 7.2: Clarification text was added to address 
the notification process for biological sample 
management in the event of study participant 
withdrawal from the study.
Section 7.3 and Appendix 1 Informed Consent 
Process: Clarification text was added to address 
study retention and data collection requirements for 
the study. In addition, further clarification has been 
added to emphasize the informed consent process 
during circumstances where the maternal participant 
is no longer able to provide consent but the infant 
participant’s continued participation in the study 
could be retained by the parent(s)/legal guardian as 
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per local regulatory, local laws, and local 
governance approval.
Section 8.1.1.1: Clarification text was added to 
provide guidance regarding the midturbinate swab 
processing requirements and the definition of 
acceptable certified/accredited laboratory bodies for 
this process in the study.
Section 8.2.1.1 and Section 8.10.1: The reporting 
requirements for Grade 4 local reactions in the study 
were clarified; the assessment and reporting are 
carried out by the investigators (or appropriately 
qualified designees).
Section 8.3.1.1, Section 8.3.1.2, Section 8.3.5.1,
Section 8.3.5.2, Section 8.10, and Section 8.11: The 
reporting requirements were clarified for this 
vulnerable patient population with regard to AEs
and SAEs likely to occur in the study in women 
with gestational age (GA) eligibility criterion 
between 24 0/7 and 36 0/7 weeks.
Section 8.3.6: Text was added to address and 
standardize reporting procedures for adverse events 
of special interest (AESIs) for this patient 
population.
Section 8.3.7 and Appendix 4: Several Pfizer text 
revisions were incorporated regarding device 
deficiencies and the safety reporting requirements 
for this study.
Section 8.10: The immunogenicity blood collection 
and physical examination window requirements 
before vaccination were aligned to provide greater 
logistical convenience for the investigational sites 
with respect to enrolling participants into the study. 
Section 8.10.1: The prepregnancy BMI text 
revisions in Section 5.2.1 were aligned with the 
study assessment requirements for maternal 
participants at screening.
Section 8.10.2, Section 8.10.3, Section 8.10.4, and 
Section 8.10.6: Clarification text was added to the 
MA-RTI reporting requirements for maternal 
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Page 7
participants in the study to provide guidance and 
ensure the investigational sites provide accurate 
information pertaining to these self-reported events.
Section 8.11.1 to Section 8.11.6: Clarification text 
was added (where applicable) to address the 
following study assessments:
o
“Birth weight must be the first birth weight and 
cannot be based on the standard-of-care 
examination” was removed as this statement is 
confusing to the investigational sites. Birth 
weight assessments have now been realigned 
with standard-of-care assessments at the study 
visit to aid compliance with study assessments 
and requirements.
o
Clarification text was added regarding the 
reporting of standard-of-care measurements for 
vital sign assessments.
o
In addition, the physical examination and vital 
sign assessment windows for the study were 
aligned to provide greater logistical convenience 
for the investigational sites to comply with study 
protocol requirements.  
o
For further clarification, the RTI study visit 
assessment requirements were amended to 
emphasize the difference between the MA-RTI 
visit criteria and the subsequent study visit after 
the event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements. 
Section 8.11.7.1: For further clarification, the RTI 
study visit assessment requirements have been 
amended to emphasize the following:
o
The RTI study visit window, including nasal 
swab collection from the MA-RTI notification 
for the infant participant.
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Page 8
o
Duplicate text was removed pertaining to the 
MA-RTI definition and the signs and symptoms 
of interest pertinent to an RTI study visit.
o
Guidance regarding the difference between the 
MA-RTI visit and the subsequent study visit 
after the event has been reported. This is to 
improve clarity and consistency with the RTI 
study visit requirements.
Section 8.11.8: Clarification text was added to 
address the RTI study visit window, including nasal 
swab collection from the MA-RTI notification for 
the infant participant.
o
For further clarification, the RTI study visit 
assessment requirements have been amended to 
emphasize the difference between the MA-RTI 
visit and the subsequent study visit after the 
event has been reported. This is to improve 
clarity and consistency with the RTI study visit 
requirements and provide guidance to the 
investigational sites.
Section 9.1.2.1, Section 9.1.2.2, Section 9.4.1,
Section 9.2, and Section 9.5: Text was added to 
clarify the statistical analysis procedures in line with 
the current revisions.
Appendix 2: Clarification text was added to support 
the safety and pregnancy outcome reporting 
requirements for participants who may experience
exposure during pregnancy while in the study.
Appendix 5 Further clarification was added to the 
background factors of interest during the infant’s 
participation in the study. 
Appendix 6: Clarification text was added to the 
examination and treatment criteria checklist for 
reported MA-RTI visits.  This is to ensure there is 
some consistency to the source records provided for 
these events in relation to the protocol requirements.
Throughout: Several changes were made to 
incorporate the replacement of the Clinical Trial 
Serious Adverse Event Report Form (CT SAE 
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Report Form) to Vaccine SAE Reporting Form, as 
part of the new vaccine SAE reporting requirements 
for Pfizer. 
Throughout: Minor editorial revisions were 
incorporated as appropriate. 
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................16
1. PROTOCOL SUMMARY...................................................................................................17
1.1. Synopsis ..................................................................................................................17
1.2. Schematic for Study Participants ............................................................................24
1.2.1. Study Design – Maternal Participants ........................................................24
1.2.2. Study Design – Infant Participants .............................................................25
1.2.3. Schedule of Activities for Maternal Participants........................................26
1.2.3.1. Schedule of Activities for Maternal Participants: RTI 
Surveillance for Medically Attended Respiratory Tract Illness 
Visits (Vaccination Until the End-of-Study Visit) ............................29
1.2.4. Schedule of Activities for Infant Participants.............................................30
1.2.4.1. Schedule of Activities for Infant Participants: Respiratory 
Tract Illness Study Visits During the Study......................................32
2. INTRODUCTION ...............................................................................................................34
2.1. Study Rationale .......................................................................................................34
2.2. Background .............................................................................................................35
2.3. Benefit/Risk Assessment.........................................................................................36
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................37
3.1. Infant Participants ...................................................................................................37
3.2. Maternal Participants...............................................................................................41
3.3. Protocol-Defined Efficacy Endpoints .....................................................................42
4. STUDY DESIGN.................................................................................................................43
4.1. Overall Design.........................................................................................................43
4.1.1. Approximate Duration of Participation for Each Participant .....................44
4.1.2. Approximate Number of Participants.........................................................45
4.2. Scientific Rationale for Study Design.....................................................................45
4.3. Justification for Dose ..............................................................................................45
4.4. End of Study Definition ..........................................................................................46
5. STUDY POPULATION......................................................................................................46
5.1. Inclusion Criteria.....................................................................................................47
5.1.1. Inclusion Criteria – Maternal Participants..................................................47
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5.1.2. Inclusion Criteria – Infant Participants.......................................................49
5.2. Exclusion Criteria....................................................................................................49
5.2.1. Exclusion Criteria – Maternal Participants.................................................49
5.2.2. Exclusion Criteria – Infant Participants......................................................51
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants ................51
5.3. Lifestyle Considerations..........................................................................................52
5.4. Screen Failures ........................................................................................................52
6. STUDY INTERVENTION..................................................................................................52
6.1. Study Intervention(s) Administered........................................................................52
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........52
6.1.2. Placebo........................................................................................................53
6.1.3. Administration............................................................................................53
6.1.4. Medical Devices .........................................................................................53
6.2. Preparation/Handling/Storage/Accountability ........................................................54
6.2.1. Preparation and Dispensing........................................................................55
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................55
6.3.1. Blinding of Study Site Personnel................................................................55
6.3.2. Blinding of the Sponsor..............................................................................55
6.3.3. Allocation to Investigational Product .........................................................55
6.3.4. Breaking the Blind......................................................................................56
6.4. Study Intervention Compliance...............................................................................56
6.5. Concomitant Therapy..............................................................................................56
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................56
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................57
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................57
6.5.4. Permitted Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................58
6.5.5. Recording Nonstudy Vaccinations and Concomitant Medications –
Infant Participants............................................................................................58
6.6. Dose Modification...................................................................................................58
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6.7. Intervention After the End of the Study..................................................................58
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................58
7.1. Discontinuation of Study Intervention ....................................................................58
7.2. Participant Discontinuation/Withdrawal From the Study.......................................58
7.3. Withdrawal of Consent............................................................................................59
7.4. Lost to Follow-up....................................................................................................59
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................60
8.1. Efficacy Assessments..............................................................................................61
8.1.1. Efficacy Assessments – Infant Participants................................................61
8.1.1.1. Midturbinate Nasal Swab Collection and Testing 
Requirements for Endpoint Confirmation – Infant Participants........61
8.1.1.2. Events for Adjudication and Submission Guidance –
Infant Participants..............................................................................62
8.1.2. Exploratory Efficacy Assessments – Maternal Participants.......................63
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal 
and Infant Participants .....................................................................................63
8.1.4. Immunogenicity Assessments ....................................................................64
8.1.4.1. Total Volume of Blood Collected – Maternal Participants.......64
8.1.4.2. Total Volume of Blood Collected – Infant Participants............64
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant 
Participants ........................................................................................64
8.1.4.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development – Maternal and Infant 
Participants ........................................................................................65
8.1.4.5. Respiratory Pathogens – Infant Participants .............................65
8.1.4.6. Biological Samples – Maternal and Infant Participants............65
8.2. Safety Assessments .................................................................................................66
8.2.1. Participant Electronic Diary – Maternal Participants .................................66
8.2.1.1. Local Reactions – Maternal Participants...................................67
8.2.1.2. Systemic Events – Maternal Participants..................................68
8.2.1.3. Temperature – Maternal Participants ........................................70
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant 
Participants.......................................................................................................70
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8.3. Adverse Events and Serious Adverse Events..........................................................70
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......71
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................72
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................73
8.3.2. Method of Detecting AEs and SAEs ..........................................................73
8.3.3. Follow-up of AEs and SAEs.......................................................................73
8.3.4. Regulatory Reporting Requirements for SAEs...........................................74
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Investigational Product ..........................................................................74
8.3.5.1. Exposure During Breastfeeding ................................................74
8.3.5.2. Occupational Exposure .............................................................74
8.3.6. Adverse Events of Special Interest.............................................................75
8.3.7. Medical Device Deficiencies......................................................................76
8.3.7.1. Time Period for Detecting Medical Device Deficiencies .........76
8.3.7.2. Follow-up of Medical Device Deficiencies...............................76
8.3.7.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................77
8.3.7.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................77
8.3.8. Medication Errors .......................................................................................78
8.4. Treatment of Overdose............................................................................................79
8.5. Pharmacokinetics ....................................................................................................79
8.6. Pharmacodynamics..................................................................................................79
8.7. Genetics...................................................................................................................79
8.7.1. Specified Genetics ......................................................................................79
8.8. Biomarkers ..............................................................................................................79
8.9. Health Economics ...................................................................................................79
8.10. Procedures – Maternal Participants.......................................................................79
8.10.1. Screening and Vaccination Visit (Clinic; Day -28 to Day 1 – Visit 
1) ......................................................................................................................79
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After 
Vaccination).....................................................................................................84
8.10.3. Delivery (Maternity Unit).........................................................................84
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8.10.4. 6-Month-Postdelivery Visit (Clinic or Telephone; 180 to 210 Days 
After Delivery).................................................................................................86
8.10.5. Unscheduled Reactogenicity Visits..........................................................86
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria –
Maternal Participants .......................................................................................88
8.11. Procedures – Infant Participants............................................................................89
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After 
Birth)................................................................................................................89
8.11.2. Visit 2 – 1-Month Follow-up (Clinic, 28 to 48 Days After Birth) ...........90
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic, 180 to 210 Days After 
Birth)................................................................................................................91
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 
Days After Birth) .............................................................................................92
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days 
After Birth; Infant Participants Born During the First Year of the Study 
Only) ................................................................................................................94
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 
742 Days After Birth; Infant Participants Born During the First Year of 
the Study).........................................................................................................94
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 
Months After Delivery)....................................................................................95
8.11.7.1. RTI Associated With a Medical Visit – Hospital, Home, 
or Clinic Visit ....................................................................................95
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit 
Criteria .............................................................................................................96
8.12. Communication and Use of Technology...............................................................98
9. STATISTICAL CONSIDERATIONS ................................................................................99
9.1. Estimands and Statistical Hypotheses.....................................................................99
9.1.1. Estimands – Infant Participants ..................................................................99
9.1.1.1. Efficacy .....................................................................................99
9.1.1.2. Immunogenicity ........................................................................99
9.1.1.3. Safety.......................................................................................100
9.1.2. Estimands – Maternal Participants ...........................................................100
9.1.2.1. Immunogenicity ......................................................................100
9.1.2.2. Safety.......................................................................................101
9.2. Sample Size Determination...................................................................................101
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9.3. Populations for Analysis .......................................................................................102
9.4. Statistical Analyses ...............................................................................................103
9.4.1. Efficacy Analyses .....................................................................................103
9.4.2. Safety Analyses ........................................................................................106
9.4.3. Other Analyses..........................................................................................107
9.4.3.1. Immunogenicity Analyses.......................................................107
9.4.3.2. Healthcare Utilization Analyses..............................................108
9.5. Interim Analyses ...................................................................................................108
9.5.1. Data Monitoring Committee.....................................................................109
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................111
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............111
10.1.1. Regulatory and Ethical Considerations ..................................................111
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................111
10.1.2. Financial Disclosure ...............................................................................112
10.1.3. Informed Consent Process ......................................................................112
10.1.4. Data Protection .......................................................................................113
10.1.5. Dissemination of Clinical Study Data ....................................................113
10.1.6. Data Quality Assurance ..........................................................................115
10.1.7. Source Documents..................................................................................116
10.1.8. Study and Site Closure............................................................................116
10.1.9. Publication Policy...................................................................................117
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................117
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................119
10.2.1. Definition of AE .....................................................................................119
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs).................120
10.2.3. Definition of SAE...................................................................................120
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs.....................121
10.2.5. Reporting of SAEs..................................................................................125
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......126
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10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting............................................128
10.4.1. Definition of AE and Adverse Device Effect (ADE) .............................128
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device 
Effect, and Unanticipated Serious Adverse Device Effect............................128
10.4.3. Definition of Device Deficiency.............................................................129
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .......................................................................................129
10.4.5. Reporting of SAEs..................................................................................132
10.4.6. Reporting of SADEs...............................................................................132
10.5. Appendix 5: Background Factors........................................................................133
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria 
Checklist for MA-RTI Visit – Infant Participants...................................................134
10.7. Appendix 7: Abbreviations .................................................................................136
11. REFERENCES ................................................................................................................139
LIST OF TABLES
Table 1.
Endpoint Events and Definitions in Infant Participants ...........................37
Table 2.
Endpoint Events and Definitions in Maternal Participants.......................41
Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained....................................................................................................64
Table 4.
Grading Scale for Local Reactions...........................................................68
Table 5.
Grading Scale for Systemic Events ..........................................................69
Table 6.
Ranges for Fever.......................................................................................70
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals 
at an Interim Analysis.............................................................................109
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Indication
Pfizer’s respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSVpreF) 
is a prophylactic vaccine that is being investigated for the prevention of medically attended
RSV-associated lower respiratory tract illness (LRTI) in infants by active immunization of 
pregnant women.
Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given the global burden of disease, maternal immunization offers an attractive 
strategy for infant disease prevention.  Both preclinical studies in animals and interim data 
from a Phase 1/2 study in healthy nonpregnant adults have demonstrated acceptable 
tolerability and safety of RSVpreF.  A robust immune response has also been observed in 
participants from the aforementioned trial. RSVpreF is currently under assessment in healthy 
pregnant women 18 through 49 years of age (Study C3671003: A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blinded Trial to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT04032093).
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
lower respiratory tract illness (MA-LRTI) in infants.  
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Objectives, Estimands, and Endpoints 
Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC): 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:   

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants 
born to maternal 
participants receiving 
1 dose of investigational 
product, the percentage 
of participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

Adverse events (AEs) from birth to 
1 month of age.

Serious adverse events (SAEs) and 
newly diagnosed chronic medical 
conditions (NDCMCs):
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants 
enrolled during the first year of 
the study).
Secondary Efficacy Objectives
– Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and 
in compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with 
protocol-defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of medically attended 
respiratory tract illness 
(MA-RTI) due to RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs 
from vaccination up to 730 days after 
birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 6 months 
of age.
MA-LRTIs due to RSV occurring 181 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth. 
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
Hospitalization due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause 
MA-LRTI.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth. 
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI as confirmed by the 
EAC occurring within 181 days after 
birth.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population. 
Positivity for non-RSV respiratory 
pathogens obtained at unplanned 
MA-RTI visits occurring within 181 days 
after birth.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth. 
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To assess the impact of 
RSVpreF on RSV illness based 
on socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors 
(eg, breastfeeding, maternal smoking, 
number of household members).
To assess the effect of RSVpreF 
on healthcare utilization. 
Mean/median composite score 
summarizing healthcare utilization, 
which may include the following: 
number and type of medical visits, length 
of hospital stay, requirement for 
mechanical ventilation, requirement for 
respiratory diagnostic procedures, 
requirement for intravenous (IV) fluids, 
requirement for prescriptions, and 
antibiotic use.
Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimand
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery 
study visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum
neutralizing titers and prefusion F 
immunoglobulin G (IgG) titers 
measured:

before vaccination.

at delivery.
Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
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(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis section [Section 9.2]).  There is no specific case target for 
the additional primary endpoint of severe MA-LRTI. The total enrollment number of 
maternal participants may vary depending on the incidence rate of the primary endpoint in 
the infant participants, the true underlying VE, and a potential early stop for efficacy or 
futility. In the event that efficacy in the infant population is demonstrated at the interim 
analysis, enrollment of maternal participants may continue in order to obtain safety 
evaluations in an adequate number of maternal and infant participants to support vaccine 
registration with national health authorities. 
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It is anticipated that approximately 6900 
mother-infant pairs may be needed to accumulate 124 per-protocol cases.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF will be 120 µg 
(60 µg A and 60 µg B). 
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.  
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study, all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term respiratory 
tract illness (RTI) surveillance and safety oversight to address safety and the possibility of 
conferred enhanced protection (antibody persistence) during a second RSV season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. 
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Planned Duration
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on gestational age (GA) at the time of vaccination and 
when the infant is actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
Data Monitoring Committee
This study will use an external data monitoring committee (E-DMC) to monitor vaccine 
safety and efficacy and study futility.  
Statistical Methods
The primary hypothesis to be tested is that VE with respect to MA-LRTI due to RSV or 
severe MA-LRTI due to RSV in infants within at least 90 days after birth is more than 20%, 
relative to placebo. The 2 primary endpoints will be tested in parallel using a Hochberg 
multiplicity adjustment procedure. VE will be estimated using the exact conditional binomial 
method. There will also be hierarchical testing of the primary endpoints to 120 days, 
150 days, and 180 days, conditional on success of the analysis for the shorter intervals. A 
single interim analysis of the MA-LRTI-due-to-RSV endpoint with the opportunity to stop 
the study for efficacy or futility may be included. At the end of the trial, the RSV vaccine 
may be deemed efficacious if there are 43 or fewer cases of MA-LRTI due to RSV in the 
RSV vaccine group out of the 124 total primary-endpoint cases.  This corresponds to 
estimated VE = 47% with 95.1% confidence interval (CI) = (22%, 64%). For severe MA-
LRTI, assuming a total of 50 cases occur, the vaccine may be deemed efficacious if there are 
14 or fewer cases in the RSV vaccine group.  This corresponds to estimated VE = 61% with 
95.1% CI = (26%, 81%).
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1.2. Schematic for Study Participants
1.2.1. Study Design – Maternal Participants
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1.2.2. Study Design – Infant Participants
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Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
1.2.3. Schedule of Activities for Maternal Participants
Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic or Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current alcohol, tobacco, marijuana, or any illicit drug usage
X
Record vital signs
X
Targeted physical examination performed on the same day or within 
7 days before the vaccination visit
X
Record details of any antenatal and/or postnatal steroid treatment, 
monoclonal antibodies, blood products, or Rho(D) immune globulin
X
X
X
X
Record details of the maternal participant’s GBS status and if any 
medication was given for IAP
X
Record nonstudy vaccine information
X
X
X
X
Review eligibility criteria
X
X
X
Review temporary delay criteria
X
Prevaccination blood draw for serologic assessment (~15 mL) on the 
same day or within 7 days before the vaccination visit
Xe
Assign randomization and container number
X
E-diary training, dispense digital thermometer and measuring devicef
X
Obtain and record baseline assessment of prespecified systemic 
events prior to vaccination in the e-diary
X
Administer investigational product
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic or Telephone
Postvaccination observation (at least 30 minutes) and assessment of 
immediate AEs
X
Delivery blood draw for serologic assessment (~15 mL)
Xe
Record pregnancy outcome information
X
Review e-diary datag
X--------------------------X
Record AEs, as appropriateh
X--------------------------X
Record SAEs, as appropriateh
X
X
X
X
Record details pertaining to MA-RTI visiti
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of 
the schedule of activities
Abbreviations: CRF = case report form; e-diary = electronic diary; GBS = group B streptococcal; IAP = intrapartum antibiotic prophylaxis; MA-RTI =
medically attended respiratory tract illness.
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic or Telephone
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.    Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.    AEs occurring up to 48 hours after a blood draw that are related to the study procedures must be reported in the CRF.
f.    Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and or the field worker (as per local practice) will record (in an e-diary) a baseline 
assessment of prespecified systemic events prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination (where Day 1 is the 
day of vaccination).  Remind maternal participants that the study staff/field worker may contact them to obtain additional information on events entered 
into the e-diary.  Ask maternal participants to contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 
following vaccination, to determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal participant may be 
referred to the appropriate healthcare facility at the discretion of a field worker if there are any concerns.
g.    Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part 
of the ongoing safety review.
h.    The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected. Please see Section 8.3.1 for reporting requirements 
and timelines.
i.    A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product.
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1.2.3.1. Schedule of Activities for Maternal Participants: RTI Surveillance for Medically Attended Respiratory Tract Illness
Visits (Vaccination Until the End-of-Study Visit)
Visit Description
Assessments of MA-RTIa
Visit Window
As Soon as Possible After Confirmed MA-RTI 
Type of Visit
Telephone
Record details of a confirmed MA-RTI 
X
Details of an acute illness visit AND a report of 1 or more of the following 
RTI signs and symptoms: 

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
X
Obtain standard-of-care records, including local NAAT testing results (if 
applicable)b
X
Record nonstudy vaccine information
X
Record AEs and SAEs, as appropriatec
X
Complete the CRF with details 
X
Abbreviations: CRF = case report form; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness.
a.
Confirmed cases of MA-RTI will be collected from vaccination until the maternal participant completes the study. The assessment of the event would 
involve a telephone call, or a clinic visit if determined by the investigator to be warranted. 
b.
Site staff will review and collect data pertaining to the illness and any local NAAT testing results (RSV, influenza, etc), if available.
c.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  MA-RTI events will not be captured as safety 
events, unless the investigator or an appropriate designee deems them to be related to the investigational product. Please see Section 8.3.1 for reporting 
requirements and timelines.
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1.2.4. Schedule of Activities for Infant Participants
Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the 
First Year of the Studya.
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-
up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 
Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic 
Clinic 
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Assign infant participant identifier
X
Demography 
X
Collect background factorsc
X
X
X
X
X
X
Collect birth outcome information including 
infant’s birth data and appearance, pulse, 
grimace, activity, and respiration (Apgar) score
X
Obtain and record infant’s length, head 
circumference, and weight
X
X
X
X
(if clinic visit)
X
(if clinic visit)
Physical examination including vital signs
performed within 48 hours after birth
X
Targeted physical examination (record in the site 
source document)
X
X
X
(if clinic visit)
X
(if clinic visit)
Record immune globulin, monoclonal antibodies 
(eg, Synagis), or blood products (eg, whole 
blood, packed cells)
X
X
X
X
X
X
Review eligibility
X
Cord blood sample (~10 mL) for serologic 
assessmentd
X
Record AEs, as appropriatee
X
Record NDCMCs and SAEs, as appropriatee
X
X
X
X
X
X
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Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the 
First Year of the Studya.
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month 
Follow-upb
6-Month Follow-upb
12-Month 
Follow-up 
18-Month 
Follow-up
24-Month Follow-
up
Visit Window (Days)
Birth to 7 
Days After 
Birth
28 to 48 
Days
After Birth
180 to 210 Days 
After Birth
350 to 378 
Days
After Birth
525 to 574 
Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic 
Clinic 
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or Telephone
Surveillance reminder contact
Contact with the infant 
participants’ parent(s) or 
legal guardian(s)
approximately every week 
until Visit 3
From Visit 3, contact with the infant participant’s parent(s) or legal guardian(s), 
approximately every 28 to 35 days until the end of the study
Assessment of MA-RTIsf
Assessment of MA-RTI 
events during the active RSV 
surveillance period as 
detailed in Section 1.2.4.1 of 
the schedule of activities
Assessment of MA-RTI events as detailed in Section 1.2.4.1 of the schedule of 
activities
Abbreviations: MA-RTI = medically attended respiratory tract illness; NDCMC = newly diagnosed chronic medical condition; RSV = respiratory syncytial 
virus.
a.
Applicable only for infant participants enrolled during the first year of the study.
b.    If medically necessary (eg, during an outbreak or pandemic situation), study visits cannot be conducted in the clinic in accordance with the protocol 
requirements. These visits and associated assessments should be conducted in the home or via telephone. 
c.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV illness. 
d.    Cord blood must be obtained on the day of birth. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical cord has 
been clamped and cut. If cord blood is unavailable, a blood sample may be collected from the infant participant preferably within the first 24 hours but up 
to 7 days after birth. The infant’s weight must be used to determine the volume of blood that can be collected.
e.    The investigator and site staff/field worker will ensure the active elicitation and collection of AEs, NDCMCs, and SAEs through 28 days after birth.  From 
29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected.  An NDCMC is defined as a disease or medical 
condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
f.    A confirmed MA-RTI is defined as an expected study event based on the assessments detailed in the schedule of assessment in Section 1.2.4.1. These 
events will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product.
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1.2.4.1. Schedule of Activities for Infant Participants: Respiratory Tract Illness Study Visits During the Study 
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After 
Confirmed MA-RTI and Within 
72 Hours (Preferable) or Up to 10 
Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Surveillance reminder contact
Contact the infant participants’ parent(s) 
or legal guardian(s) approximately every 
week until Visit 3
From Visit 3, contact the infant participants’ parent(s) or legal 
guardian(s), approximately every 28 -35 days until the end of the 
study
Record confirmed MA-RTI as detailed in Appendix 6, 
as appropriate
X
X
X
Record details of the RTI, including 1 or more of the 
following RTI signs and symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid 
breathing for any duration

Cough

Inability to feed for any duration because of 
respiratory symptoms

Apnea

Any other respiratory symptom of concern 
X
X
X
Obtain standard-of-care records and complete CRFc
X
X
X
Record local NAAT testing results, if performed and 
availabled
X
X
X
Perform RTI study visit, record targeted assessment
results (heart rate, respiratory rate, SpO2, chest wall 
indrawing), and collect nasal swab (for RT-PCR)e
X
X
Record concomitant medication associated with the 
treatment of the MA-RTI
X
X
X
Collect background factors associated with MA-RTIf.
X
X
X
Record immune globulins, monoclonal antibodies (eg, 
Synagis), or blood products (eg, whole blood, packed 
cells)
X
X
X
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Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After 
Confirmed MA-RTI and Within 
72 Hours (Preferable) or Up to 10 
Days
As Soon as Possible After Confirmed MA-RTI and 
Within 72 Hours (Preferable) or Up to 10 Days
Type of Visit
RTI Study Visit for MA-LRTI and 
Severe MA-LRTIa
Hospital, Home, or Clinic
RTI Study Visit for 
MA-LRTI 
Telephone
RTI Study Visit for 
Hospitalization or Severe 
MA-LRTIb
Hospital, Home, or Clinic
Record AEs , NDCMCs, and SAEs, as appropriateg
X
X
X
Compile MA-RTI visit source documentation upon 
request by adjudication committee (qualifying RSV-
positive cases only)
X
X
Abbreviations: CRF = case report form; ICU = intensive care unit; IV = intravenous; MA-LRTI = medically attended lower respiratory tract illness; MA-RTI 
= medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; NDCMC = newly diagnosed chronic medical condition; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness; RT-PCR = reverse transcription–polymerase chain reaction; SpO2 = oxygen saturation.
a.
If the infant participant is reported to be experiencing or has had an MA-RTI from birth until Visit 3, the site should arrange a study visit as soon as 
possible and within 72 hours (preferable) or up to 10 days. Ideally, the RTI study visit will be conducted at the investigational study site; however, it is 
possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit 
where the infant participant is residing.
b    If the infant participant is reported to be experiencing or has had an MA-RTI associated with severe LRTI criteria or been hospitalized for an RTI from 
Visit 3 until the end of study participation, the site should arrange a visit as soon as possible and within 72 hours (preferable) or up to 10 days of site 
awareness. Ideally, assessment of these potential endpoint events (hospitalization due to RTI or severe MA-LRTI) will be conducted at the investigational 
study site; however, it is possible that the visit could be conducted in another healthcare setting (for example, if the infant participant is hospitalized) or 
the site staff may visit where the infant participant is residing. 
Note: For nonsevere MA-RTIs, a telephone contact with the infant participants’ parent(s) or legal guardian(s) is acceptable to complete the study visit.
c.
Obtain case records, including details of hospitalization, ICU stays, use of oxygen, IV fluids usage, etc.
d.
The site staff/field worker will review and collect data related to any local NAAT testing results, if performed and available.
e.
The site staff/field worker will collect nasal swabs for confirmed MA- RTIs, including confirmed cases of hospitalizations due to an RTI and severe MA-
LRTIs.
f.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV. This will be collected 
for all MA-RTI events reported.
g. 
The investigator and site staff/field worker will ensure the active elicitation and collection of NDCMCs and SAEs through the end-of-study visit for the 
infant participant. From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected. An NDCMC is defined 
as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma). Note: A 
confirmed MA-RTI will not be captured as a safety event, unless the investigator or an appropriate designee deems it to be related to the investigational 
product.
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2. INTRODUCTION
Prevention of RSV disease in young infants is a significant unmet medical need globally.  
RSV is the leading cause of bronchiolitis and viral pneumonia in infants and can lead to fatal 
respiratory distress, especially in those with risk factors including premature infants with 
underlying cardiopulmonary disease, or in the absence of effective healthcare systems.1
However, most cases of RSV disease occur in healthy, full-term infants without risk factors.2
Worldwide, RSV kills approximately 118,200 children annually, with about half of those 
deaths occurring in infants under 6 months of age, and the majority of those occurring in 
resource-limited countries.3,4 In the United States, RSV is the leading cause of infant 
hospitalization, with more than 60,000 hospitalizations of children 12 months of age and 
younger annually.5,6  There is increasing evidence that the link between severe RSV disease 
in infancy and wheezing later in childhood may be causal.7,8  Like influenza, RSV infection 
follows a seasonal pattern, causing illness primarily in the cooler months of the year in 
temperate regions and during the wet season in tropical countries with seasonal rainfall.9  
Infection is essentially universal by the time children reach 2 years of age.10
Currently, there is neither specific treatment for RSV infection nor a vaccine to protect 
against RSV disease.  Treatment consists primarily of supportive care.  A prophylactic 
humanized monoclonal antibody, palivizumab (Synagis, AstraZeneca), targeting the RSV F 
glycoprotein is available for prevention of severe RSV disease in young infants at increased 
risk.11  Limitations of its use include its high cost12 and requirement of multiple monthly 
injections,13 and so it remains recommended for use only in very premature infants and 
others at increased risk of severe illness.6,14
Nevertheless, the protective effect of Synagis provides definitive proof of principle that 
serum neutralizing antibody directed against the F protein can provide clinically meaningful 
protection against RSV lower respiratory tract disease in young infants.15  Furthermore, it is 
well known that in other disease settings, antibodies transferred from mothers to their fetuses 
across the placenta can reduce infant disease early in life,16,17,18,19,20,21 suggesting that 
maternal immunization is a reasonable approach to RSV disease prevention among young 
infants.
There are 2 antigenic variants of RSV, namely, RSV subgroup A (RSV A) and RSV 
subgroup B (RSV B).  The RSV vaccine being investigated in this study is a bivalent vaccine 
composed of stable RSV prefusion F antigens representing the 2 subgroups to help ensure the 
broadest coverage against RSV illness.
RSVpreF is a prophylactic vaccine being developed to prevent medically attended
RSV-associated LRTI in infants by active immunization of pregnant women.
2.1. Study Rationale 
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given a global burden of disease in the millions of cases each year, maternal 
immunization offers an attractive strategy for infant disease prevention.  Both preclinical 
studies in animals and interim data from a Phase 1/2 study in healthy nonpregnant adults 
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have demonstrated acceptable tolerability and safety of RSVpreF.  A robust immune 
response has also been observed in the population of the aforementioned trial, at 1 month 
after vaccination. The combined RSV A and B serum neutralization geometric mean titers 
(GMTs) have been shown to be 12 to 20 times higher than those with 100 μg/mL of
palivizumab, the concentration of the monoclonal antibody that is known to provide near to 
complete protection of high-risk infants from severe RSV disease.22,23 RSVpreF is currently 
under assessment in healthy pregnant women 18 through 49 years of age (Study C3671003, 
A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093).
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate 
the efficacy and safety of maternal immunization with RSVpreF against medically attended
RSV-associated LRTI in infants.  
2.2. Background 
RSV is an important cause of morbidity and mortality worldwide, with a substantial burden 
of disease borne by young infants.  Rates of severe RSV illness are highest in infants 
6 months of age, with a peak in hospitalization between 1 and 2 months of life, though the 
highest case-fatality rates are observed in the neonatal period (<1 month).2 Infants born 
prematurely and those with underlying cardiac or pulmonary disease are at further increased 
risk of severe clinical disease due to RSV.  A 2017 retrospective case analysis that examined 
RSV mortality data from 23 countries demonstrates the global nature of the seriousness of 
RSV disease, with significant morbidity and mortality occurring in both lower- and 
middle-income countries (LMICs) and high-income countries.3,4
No specific treatments for RSV exist, and available prophylactic measures (ie, RSV 
monoclonal antibody) are limited to use in only those infants at highest risk; additionally, in 
LMICs, use of available RSV prophylaxis is cost-prohibitive.  While active immunization 
against RSV in infants might be an option, multiple efforts, extending over half a century, to 
develop a safe and effective RSV vaccine to protect infants from disease have yielded little 
success.  The early peak of disease presents a further obstacle to an active vaccination 
strategy for infants.  Given these challenges, maternal immunization to protect infants early 
in life offers an attractive strategy for infant disease prevention.  
The present RSV vaccine efforts were initiated in early 2014 based on a new scientific 
discovery (determination of the RSV prefusion F crystal structure)24 and a changing 
regulatory and policy environment that today supports the development of vaccines for 
maternal immunization to protect very young infants.  The trimeric RSV F surface 
glycoprotein in a prefusion conformation is now known to be the primary target of 
neutralizing antibodies and is the basis for the engineered antigens in Pfizer’s vaccine 
candidate.   Applying structure-guided vaccine design, Pfizer has developed a stabilized RSV 
prefusion F vaccine candidate.  The core hypothesis underlying Pfizer’s RSV vaccine 
development effort for prevention of infant disease is that vaccine antigens based on RSV 
prefusion F, when administered to pregnant women in the second or third trimester of 
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pregnancy, will elicit sufficiently high neutralizing antibody titers that, when the antigens are 
actively transferred transplacentally to the fetus, will protect infants against RSV disease. 
The aim is for neutralizing antibody levels to be at sufficient levels such that infants will be 
protected from birth and possibly through their first RSV season.
2.3. Benefit/Risk Assessment
RSVpreF is being evaluated in ongoing clinical studies.  Pfizer’s maternal immunization 
approach circumvents the risk of vaccine-mediated disease enhancement that was observed 
in the 1960s following direct immunization of RSV-naive infants with a formalin-inactivated 
RSV vaccine (FI-RSV).25  FI-RSV elicited a predominantly nonneutralizing antibody 
response and a Th2-biased cell-mediated response, both of which are considered potential 
contributing factors to disease enhancement.26  During preclinical studies, in a standard 
cotton rat infectious RSV challenge model, FI-RSV showed pathological signs of causing 
disease enhancement, and the current Pfizer vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease enhancement has not been reported to occur in 
RSV-experienced individuals after immunization with any RSV vaccine candidate.  Because 
pregnant women are universally RSV-experienced, they are not at risk for a 
disease-enhancing immune response to the vaccine that could exacerbate infection in 
themselves or their infants.  A previous study of maternal immunization with a Wyeth (later 
merged with Pfizer) investigational RSV vaccine (PFP-2) showed an acceptable safety 
profile, even though this candidate contained a postfusion RSV F antigen that elicited a 
relatively weak RSV-neutralizing antibody response and a higher nonneutralizing 
RSV-binding antibody response in pregnant women.27  A recently completed Phase 3 
maternal RSV trial (Novavax) with an RSV vaccine containing F not stabilized in the 
prefusion form, given to over 4600 healthy pregnant volunteers, showed a similar safety 
profile in the RSV vaccine and placebo groups.28
Vaccination with the RSV prefusion F antigens elicits a higher ratio of neutralizing to 
nonneutralizing antibodies, more closely matching the profile in naturally exposed 
individuals.  The safety profile of RSVpreF observed to date is similar to that of prior RSV F 
subunit vaccines tested in RSV-experienced adults.
There are limited data on the global burden of maternal RSV infection, likely in part because 
of infrequent diagnostic testing. However, in one multisite study, RSV-associated disease in 
pregnancy was shown to result in prolonged hospitalization and an increased likelihood of 
preterm birth in women who tested RSV-positive.29 It is possible that vaccination may 
benefit the pregnant women who receive it. RTI in mothers who receive RSVpreF will be 
explored in this study.  The benefit of maternal vaccination is accrued to the infant by means 
of transplacental antibody transfer.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the investigator’s brochure (IB), which is the 
single reference safety document (SRSD) for this study. 
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Infant Participants
The study objectives and endpoints for infant participants employ the event definitions in 
Table 1.
Table 1.
Endpoint Events and Definitions in Infant Participants
Study 
Endpoints/Assessments
Study Definitions
Medically attended visit
Infant participant has been taken to or seen by a healthcare provider 
(eg, outpatient or inpatient visit, emergency room, urgent care, or home 
visit)
MA-RTI visit for infant 
participant
A medically attended visit AND 1 or more of the following RTI signs and 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any 
duration

Cough

Inability to feed for any duration because of respiratory symptoms

Apnea

Any other respiratory symptom of concern 
RSV-positive testa

RSV RT-PCR–positive test result by Pfizer central laboratory
OR

RSV-positive test result by certified laboratory with NAAT for RSV
MA-RTI due to RSVb

An MA-RTI visit 
AND

RSV-positive test result as described in Section 8.1.1.1
MA-LRTI due to any cause

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age], 
≥50 bpm for ≥2 months to 12 months of age, or ≥40 bpm for ≥12 
months to 24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
MA-LRTI due to RSVb

Infant with an MA-RTI visit 
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age] or 
≥50 bpm for ≥2 to 12 months of age, or ≥40 bpm for ≥12 months to 
24 months of age) OR

SpO2 <95% OR

Chest wall indrawing 
AND 

RSV-positive test result as described in Section 8.1.1.1
Hospitalized RTI due to RSVb
An RTI due to RSV that results in hospitalization
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Table 1.
Endpoint Events and Definitions in Infant Participants
Study 
Endpoints/Assessments
Study Definitions
Severe MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥70 bpm for <2 months of age [<60 days of age], 
≥60 bpm for ≥2 months to 12 months of age, or ≥50 bpm for ≥12 
months to 24 months of age) OR

SpO2 <93% OR

High-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive) OR

ICU admission for >4 hours OR

Failure to respond/unconscious 
AND

RSV-positive test result as described in Section 8.1.1.1
Protocol-defined primary 
endpoint

Any MA-LRTI or severe MA-LRTI due to RSV as determined by an 
EAC
Abbreviations: bpm = breaths per minute; EAC = endpoint adjudication committee; ICU = intensive care 
unit; MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically attended 
respiratory tract illness; NAAT = nucleic acid amplification technology; RR = respiratory rate; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness; SpO2 = oxygen saturation.
a.
RSV-positive testing is defined as a positive RSV test (see Section 8.1.1.1) conducted on a sample 
obtained during the medically attended visit or within 10 days (where Day 1 is the day of the MA-RTI 
visit) as detailed in Section 8.11.7.
b.
The EAC will determine if the endpoint criteria have been met upon review of the site source 
documentation from the MA-RTI visit and RTI study visits, including all available RSV test results . 
Study Objectives – Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:   

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants born 
to maternal participants 
receiving 1 dose of 
investigational product, 
the percentage of 
participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

AEs from birth to 1 month of age.

SAEs and NDCMCs:
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants enrolled 
during the first year of the study).
Secondary Efficacy Objectives
–
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with protocol-
defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI due to 
RSV.
RSV-positive MA-RTI: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI.
The incidence of all-cause MA-RTIs from 
vaccination up to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV in infants after 6 months of 
age.
MA-LRTIs due to RSV occurring 181 to 
730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after 
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
Hospitalization due to RSV occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause MA-LRTI.
MA-LRTIs due to any cause occurring 181 
to 730 days after birth.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI as confirmed by the 
EAC occurring within 181 days after birth.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned MA-RTI
visits occurring within 181 days after 
birth.
To evaluate RSV serum
neutralizing titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A and RSV B serum neutralizing 
titers measured at birth.
To assess the impact of RSVpreF 
on RSV illness based on 
socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors (eg, 
breastfeeding, maternal smoking, number 
of household members).
To assess the effect of RSVpreF 
on healthcare utilization.
Mean/median composite score 
summarizing healthcare utilization, which 
may include the following: number and 
type of medical visits, length of hospital 
stay, requirement for mechanical 
ventilation, requirement for respiratory 
diagnostic procedures, requirement for IV 
fluids, requirement for prescriptions, and 
antibiotic use.
3.2. Maternal Participants
The study objectives and endpoints for maternal participants employ the event definitions in 
Table 2.
Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
Maternal medically attended visit
The maternal participant reports a visit with a healthcare 
provider (outpatient or inpatient visit, emergency room, 
urgent care, or home visit)
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Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
MA-RTI visit maternal participant
A medically attended visit AND 1 or more of the following 
RTI signs and symptoms:

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
Abbreviations: MA-RTI = medically attended respiratory tract illness; RTI = respiratory tract illness.
Study Objectives – Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimands
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery study 
visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A and RSV B serum neutralizing 
titers and prefusion F IgG titers 
measured:

before vaccination.

at delivery.
3.3. Protocol-Defined Efficacy Endpoints 
All infant participants experiencing an MA-RTI will have an RTI study visit as detailed in
Section 8.1.  This protocol will use an independent EAC to determine whether certain 
investigator-reported events meet the definition of disease-related efficacy endpoints, using 
predefined endpoint criteria as summarized in Table 1. Members of this EAC will be blinded 
to the vaccine assignment to allow for unbiased assessments.
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Recognizing that RSV disease is a dynamic illness, sites will be instructed to submit all 
available source documentation for adjudication from the MA-RTI visit and to record data 
from the worst day of illness in the electronic case report form (eCRF).  The EAC will 
determine if the endpoint criteria have been met upon review of the site source
documentation from the MA-RTI visit, including data collected at the RTI study visit, and all 
available RSV testing.  Further information about the EAC will be detailed in the 
adjudication charter, including specific descriptions of the scope of its responsibilities and 
the process and definitions to review and assess study endpoints.
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition and 
constitute a study endpoint will not be recorded as AEs.  For those AEs that are handled as 
disease-related efficacy endpoints, a data monitoring committee (DMC) will conduct 
unblinded reviews on a regular basis throughout the trial (see Data Monitoring Committee,
Section 9.5.1). 
Nonendpoint events (eg, an event that is determined not to be an MA-RTI) must be evaluated 
for safety reporting as per the protocol requirements.  Any AE that is adjudicated by the EAC
to not meet any endpoint criteria will be reported back to the investigator site of incidence; 
the investigator at the site must evaluate the event for safety as described in Appendix 2 of 
this protocol.  If the event is classified as serious, the investigator’s SAE awareness date in 
this instance is identified as the date on which the investigator site receives the nonendpoint 
SAE back from the EAC.  Handling these SAEs in this manner will allow Pfizer to meet its 
sponsor reporting obligations to regulatory authorities upon receipt of such SAEs.
Any events that remain unadjudicated at the annual safety report cutoff date will not be 
included in the safety tables of the report.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to 
assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons. 
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of 
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis (Section 9.2). There is no specific case target for the 
additional primary endpoint of severe MA-LRTI. The total enrollment number of maternal 
participants may vary depending on the incidence rate of the primary endpoint in the infant 
participants, true underlying VE, and a potential early stop for efficacy or futility. In the 
event that efficacy in the infant population is demonstrated at the interim analysis, enrollment 
of maternal participants may continue in order to obtain safety evaluations in an adequate 
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number of maternal and infant participants to support vaccine registration with national 
health authorities. 
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It is anticipated that approximately 
6900 mother-infant pairs may be needed to accumulate 124 per-protocol cases.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive a single dose of
RSVpreF or placebo.  The dose of RSV prefusion F antigen in RSVpreF for this study will be 
120 µg (60 µg A and 60 µg B).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.  
Infants born to women who receive RSVpreF or placebo in their second or third trimester
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their 12 months of participation.  For all infant participants, data will be collected for 
any medically attended respiratory illness to assess for cases of LRTI due to RSV (efficacy 
endpoint). Additionally, throughout the study all respiratory illnesses, SAEs, and NDCMCs 
reported will be assessed in this population. For infant participants enrolled during the first 
year of the study, the extended 12-month study duration will involve longer-term RTI 
surveillance and safety oversight to address safety and the possibility of conferred enhanced 
protection (antibody persistence) during a second RSV season. 
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. In addition, this study will use an 
E-DMC to monitor vaccine safety and efficacy and study futility.  
4.1.1. Approximate Duration of Participation for Each Participant
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on GA at the time of vaccination and when the infant is 
actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth. 
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4.1.2. Approximate Number of Participants
Healthy pregnant women will be randomly assigned to a study intervention. It is anticipated 
that approximately 6900 mother-infant pairs may be needed to accumulate 124 per-protocol 
cases as defined in Section 9.2 of the protocol.  Enrollment will be monitored to ensure that 
participants will be recruited from both the northern and southern hemispheres. Enrollment 
may vary depending on the incidence in the placebo group, the true underlying VE, the 
dropout rate, and a potential early stop for VE or futility.
4.2. Scientific Rationale for Study Design
Refer to Section 2.1.
4.3. Justification for Dose
The final dose and formulation of RSVpreF selected for use in this study is based on the 
safety and immunogenicity data from the ongoing C3671003 maternal immunization study
(A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in 
Pregnant Women 18 Through 49 Years of Age and Their Infants; ClinicalTrials.gov 
identifier: NCT04032093) and the first-in-human (FIH) study C3671001.
The FIH study was designed to describe the safety, tolerability, and immunogenicity of 
6 RSVpreF candidates with bivalent formulations (RSV A and B) at 3 escalating dose levels 
of 60 µg (30 µg A and 30 µg B), 120 µg (60 µg A and 60 µg B), and 240 µg (120 µg A and
120 µg B) of the RSV prefusion F antigen, with or without Al(OH)3, when administered 
alone or concomitantly with seasonal inactivated influenza vaccine.  The study utilizes a 
sentinel cohort (N=168; Phase 1) and an expanded cohort (N=1014; Phase 2).  Nonpregnant 
female and male study participants of 2 age groups, 18 through 49 years of age and 
50 through 85 years of age, were enrolled into both cohorts.  The age groups are being run in 
parallel. 
A recent interim analysis of participants 18 through 49 years of age, including safety and 
tolerability (n=533) and immunogenicity (n=513) data up to 1 month after vaccination in the 
expanded cohort and additional immunogenicity data up to 3 months after vaccination in the 
sentinel cohort, has shown the RSVpreF candidate to be immunogenic and well tolerated. 
Local reactions and systemic events were noted to be predominantly mild or moderate across 
all doses and formulations, which is consistent with the current safety profile. The safety 
results from this planned interim analysis of healthy male and nonpregnant female 
participants 18 through 49 years of age are consistent with those from the sentinel-cohort 
analysis and indicate that RSVpreF has an acceptable safety profile and is well tolerated.
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The immunogenicity results showed that RSVpreF elicited neutralizing titer geometric mean 
fold rises (GMFRs) of 10 to 20, 1 month after vaccination, depending on the formulation. 
Similarly, across all dose levels, with and without Al(OH)3, RSVpreF elicited high 1-month-
postvaccination RSV A and RSV B neutralizing GMTs. Overall, RSVpreF elicited anti–
prefusion F immunoglobulin G1 (IgG1) responses that paralleled the elicited 
RSV-neutralizing responses. The ratio of RSV 50% neutralizing antibody titer GMFRs to 
prefusion RSV F binding IgG1 titer GMFRs (calculated with combined data for subgroups A 
and B) for the sentinel and expanded 18 through 49 years of age cohorts combined ranged 
from 0.62 to 0.76. The IgG1 and neutralization responses were similar in antigen-level dose
response, in equivalence of RSV A titer GMFRs to RSV B titer GMFRs, and in a lack of 
effect of Al(OH)3. 
The high ratio of RSV-neutralizing antibody titer GMFRs to prefusion F–binding titer 
GMFRs elicited by Pfizer’s RSVpreF candidate indicates that most of the elicited antibody 
can neutralize the virus. It is assumed that this reflects the ability of the antibodies to prevent 
RSV disease in immunized participants and, in the case of maternal immunization, prevent 
disease in their infants.
The primary mechanism for protection of infants by the RSV maternal vaccine is 
neutralization of the virus by transplacentally transferred antibody, which is increased by 
immunization.  Maternal antibody decays exponentially in infants.  Therefore, it is 
anticipated that higher titers of transferred neutralizing antibodies will provide greater levels 
and durations of infant protection.  Results from the C3671001 FIH trial were used to 
determine the doses and formulations that are currently under investigation in the Phase 2b 
maternal immunization study: 120 µg or 240 µg of RSVpreF with or without Al(OH)3. 
These doses are expected to provide the greatest potential level of transplacental antibody 
transfer to infants and, therefore, the greatest potential benefit.  The dose and formulation of 
RSVpreF for the Phase 3 study was determined by the evaluation of the 1-month safety, 
tolerability, and immunogenicity results from the C3671003 maternal Phase 2b trial,
including infant RSV-neutralizing titers at birth.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last infant participant in the 
study. The study may also be terminated earlier for efficacy or futility as described in
Section 9.5.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1. Inclusion Criteria 
5.1.1. Inclusion Criteria – Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply 
(refer to the investigator site file [ISF] for further eligibility details):
Note: In countries/locales where study procedures used to determine eligibility criteria 
(eg, ultrasound examination, human immunodeficiency virus [HIV] testing, syphilis testing) 
are not performed as part of routine prenatal care, they must be performed as part of this 
clinical trial and reviewed by the investigator or qualified designee within 28 days prior to 
randomization.  Maternal participants must provide informed consent prior to 
performing any procedures, including those that are being done exclusively to meet 
study eligibility criteria.
Age and Sex:
1. Healthy women ≥18 and ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of 
gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, 
who are at no known increased risk for complications. 
Note: GA must be based upon 1 of the following composite criteria based on timing and 
availability of data on the last menstrual period (LMP) and an ultrasound examination 
performed in the first or second trimester.30  The earliest ultrasound data available during 
the current pregnancy should be used to establish GA:
a.
First-trimester data available (data obtained at ≤13 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a first-trimester ultrasound examination.

If there is a discrepancy of >5 days between the LMP-determined GA and an 
ultrasound result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA 
should be determined using the first-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and an 
ultrasound result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, 
then the GA should be determined using the first-trimester ultrasound result.
b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a second-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and the 
ultrasound result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
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
If there is a discrepancy of >10 days between the LMP-determined GA and the 
ultrasound result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >14 days between the LMP-determined GA and the 
ultrasound result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
Type of Participant and Disease Characteristics:
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Receiving prenatal standard of care based on country requirements.
4. Had an ultrasound examination performed at ≥18 weeks of pregnancy with no significant 
fetal abnormalities observed, based on the investigator’s judgment. 
5. Determined by medical history, physical examination, and clinical judgment to be 
appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) 
surface antigen test during this pregnancy and prior to randomization (Visit 1). 
7. Intention to deliver at a hospital or birthing facility where study procedures can be 
obtained. 
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol OR
11. If the maternal participant is illiterate, a thumbprinted informed consent must be 
obtained, which must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process confirming that the maternal participant 
has been informed of all pertinent aspects of the study.
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5.1.2. Inclusion Criteria – Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a 
thumbprinted informed consent must have been obtained, which must have been signed 
and dated by an impartial witness who was present throughout the entire informed 
consent process confirming that the maternal participant/parent(s)/legal guardian(s) has 
been informed of all pertinent aspects of the study for herself (maternal participant) and 
her fetus/infant prior to taking part in the study.  
Note: Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements. 
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
5.2. Exclusion Criteria 
5.2.1. Exclusion Criteria – Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not 
available, the BMI at the time of the first obstetric visit during the current pregnancy may 
be used.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any related 
vaccine.
4. Current pregnancy resulting from in vitro fertilization.  Participants known to have used 
clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are 
permitted.
5. Current pregnancy complications or abnormalities at the time of consent that will 
increase the risk associated with the participation in and completion of the study, 
including but not limited to the following:

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.
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
Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated 
hypothyroidism.  This also includes disorders of glucose intolerance (eg, diabetes 
mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if 
uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the 
investigator’s judgment, that will increase the risk associated with the participation in and 
completion of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks’ gestation.

Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or significant congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the maternal 
participant’s participation in, and completion of, the study or could preclude the 
evaluation of the maternal participant’s response.
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment.  
9. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to 
consent and/or during study participation.
11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of 
systemic corticosteroids for >14 days within 28 days prior to study enrollment.  
Prednisone use of <20 mg/day for ≤14 days is permitted. Inhaled/nebulized, 
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
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12. Current alcohol abuse or illicit drug use.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before 
investigational product administration, or planned receipt through delivery, with 
1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt 
during study participation.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
5.2.2. Exclusion Criteria – Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
2. Receipt of investigational or approved monoclonal antibodies against RSV.
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and if no other exclusion criteria are met.  
The prevaccination blood draw and vaccination should take place on the same day. In the 
event that this is not possible, the prevaccination blood draw is also permissible within 7 days 
before the vaccination visit.

Current febrile illness (body temperature ≥100.4°F [≥38°C]) or other acute illness within 
48 hours before investigational product administration.

Diagnosed malaria within the last 7 days prior to investigational product administration.

Receipt of any inactivated vaccine within 14 days or any live vaccine within 28 days 
before investigational product administration. Note: tetanus, diphtheria, and acellular 
pertussis vaccine (Tdap) coadministration may be excluded from temporary delay criteria 
based on data from the C3671004 study (A Phase 2b, Placebo-Controlled, Randomized, 
Observer-Blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 
Respiratory Syncytial Virus (RSV) Vaccine When Administered Concomitantly With 
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Tetanus, Diphtheria, and Acellular Pertussis Vaccine (Tdap) in Healthy Nonpregnant 
Women 18 Through 49 Years of Age; ClinicalTrials.gov identifier: NCT04071158).

If systemic corticosteroids (equivalent of ≥20 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical 
study but are not subsequently randomly assigned to investigational product. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
For this study, the investigational product(s) are RSVpreF and placebo (lyophile match).
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine 
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.  The
RSV drug product will be 120 µg of the RSV prefusion F antigen.  The drug product is 
supplied as a lyophilized white cake in a 2-mL glass vial, with a 13-mm lyophilization 
stopper, aluminum overseal, and flip-off cap. The drug product will be reconstituted by a 
diluent consisting of sterile water in a prefilled syringe (PFS). The lyophilized drug product 
contains excipients that, after reconstitution, will yield a solution as detailed in the IB.
The fill volume of the drug product vial and diluent PFS are designed such that the intended 
vaccine dose is delivered by injecting the entire contents of the syringe.
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6.1.2. Placebo
Placebo will be a lyophile match to the vaccine, which will consist of excipients matched to 
those used in the RSVpreF vaccine formulation, minus the active ingredients. 
The physical appearance of the reconstituted RSVpreF and placebo will be matched, and the 
study will be conducted in a double-blinded manner.
The fill volume of the placebo vial and diluent PFS is designed such that the intended 
placebo dose is delivered by injecting the entire contents of the syringe.
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
6.1.3. Administration
Maternal participants will receive 1 dose of investigational product at the vaccination visit 
(Day 1) in accordance with the study’s SoA.  The investigational product will be 
administered intramuscularly by injecting the entire contents of the syringe into the deltoid 
muscle, preferably of the nondominant arm, unless medically contraindicated, in which case 
the injection may be administered in the dominant arm. Investigational product
administration will be performed by appropriately designated study staff at the investigator 
site.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance. 
Investigational product administration details will be recorded on the case report form (CRF).
6.1.4. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluent for the RSV
vaccine or placebo, consisting of sterile water PFS only.
Instructions for medical device use are provided in the investigational product manual (IP 
manual).
Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the unblinded study personnel throughout the 
study. 
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Please refer to Section 8.3.7 for details. 
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention, as applicable for 
temperature-monitored shipments. 
2. Only maternal participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking days must indicate the minimum and maximum 
temperature since previously documented for all site storage locations upon return to 
business.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  All study interventions will be 
accounted for using an investigational product accountability form/record.  
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
6. Study interventions should be stored in their original containers and in accordance with 
the labels.
7. See the IP manual for storage conditions of the study intervention once reconstituted.
8. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use of 
the study intervention after the temperature excursion. Use of the study intervention prior 
to Pfizer approval will be considered a protocol deviation. Specific details regarding the 
definition of an excursion and information the site should report for each excursion will 
be provided to the site in the IP manual.
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9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
Additional details about accountability, storage, destruction, and excursion reporting can 
be found in the IP manual.
6.2.1. Preparation and Dispensing
Refer to the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
Investigational product and placebo will be prepared by qualified site personnel according to 
the IP manual.  The investigational product will be administered only to maternal participants 
who are blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Blinding of Study Site Personnel 
This study is a double-blinded study, as the physical appearance of RSVpreF and placebo 
will be matched. The maternal participant, investigator, study coordinator, and all site staff 
will be blinded. 
Please refer to the IP manual for further details.
6.3.2. Blinding of the Sponsor
The sponsor study team members will be blinded throughout the study to the vaccine 
assignments of all participants enrolled in the study. 
Laboratory personnel performing the serology and virology assays will remain blinded to 
vaccine assigned/received throughout the study.
6.3.3. Allocation to Investigational Product
Allocation of maternal participants to vaccine groups will proceed through the use of an 
interactive response technology (IRT) system (interactive Web-based response [IWR]).  The 
site personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the maternal participant number.  The site personnel will then be 
provided with a vaccine assignment, randomization number, and dispensable unit (DU) or 
container number as investigational product is being supplied via the IRT system.  The IRT 
system will provide a confirmation report containing the maternal participant number, 
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randomization number, and DU or container number assigned. The confirmation report must 
be stored in the site’s files. 
Note: Maternal participants will be randomized to a vaccine group as described above.  The 
infants of the maternal participants will be assigned an infant participant number at birth.
Investigational product will be dispensed and administered at study Visit 1 summarized in 
the SoA. 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Maternal participants will be assigned to receive investigational product according to the 
randomization scheme.  Investigators will remain blinded to the investigational product 
assigned to each maternal participant throughout the course of the study.
6.3.4. Breaking the Blind 
The study will be maternal participant and investigator blinded.
At the initiation of the study, the investigator will be instructed on the method for breaking
the blind for an individual participant.  The method will be an electronic process.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the participant.  The 
investigators should make every attempt to contact a member of the sponsor’s study team 
prior to breaking the blind.  When the blinding code is broken, the reason must be fully
documented and entered on the CRF.  
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy 
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal Participants

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study.

Receipt of blood/plasma products or Ig, from 60 days before investigational product 
administration, or planned receipt through delivery, with 1 exception, Rho(D) immune 
globulin (eg, RhoGAM), which can be given at any time.

Immunosuppressive therapy is prohibited during the course of the study.
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
Nonstudy vaccines may not be given concomitantly with the investigational product or 
within 7 days after investigational product administration (Day 1 to Day 7), except if 
medically necessary (eg, during an outbreak or pandemic situation).  
Note: For licensed Tdap, coadministration may be permissible based on data from the 
C3671004 study.
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal Participants

Licensed vaccines (including influenza vaccine and Tdap) may be given during the study 
starting 7 days after investigational product administration (Day 8) as per local 
recommendation for immunization in pregnant women. If medically necessary (eg, 
during an outbreak or pandemic situation), influenza vaccine, Tdap, or other vaccines 
may be given at any time.
Note: Tdap coadministration may be permissible based on data from the C3671004 study.

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. Prednisone use of <20 mg/day for ≤14 days prior to the administration of 
investigational product is permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during participant participation in the 
study.
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following vaccinations and treatments for maternal participants would require reporting 
in the CRF during the study: 

Details of any vaccinations given at any time during the pregnancy through the final 
study visit will be collected and recorded in the CRF.

Details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given to the maternal participant at any time during the 
pregnancy or during the study will be collected and recorded in the CRF.

Any prescribed medications taken to treat medically attended respiratory illnesses from 
enrollment until the final study visit will be recorded in the CRF.
Concomitant medications not meeting the criteria above will be assessed but not documented 
on the CRF.
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6.5.4. Permitted Concomitant Vaccinations and Treatments – Infant Participants

Routine treatments, routine vaccinations, and routine procedures 
(eg, circumcision) are permitted at any time according to national recommendations or 
medical standard of care or accepted practice.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during infant participant participation in the study.

Local anesthetic may be applied to the site of the blood draw, as appropriate.
6.5.5. Recording Nonstudy Vaccinations and Concomitant Medications – Infant 
Participants
The following CRF reporting guidelines are applicable to treatments given to infant 
participants during the study:

Details of any Ig (including monoclonal antibodies [eg, Synagis] or immune globulin 
[eg, hepatitis B immune globulin (HBIG)]) or blood products (eg, whole blood, packed 
cells) given to the infant participant will be collected from the time of birth until the final 
study visit and recorded in the CRF.

Any prescribed medication taken to treat medically attended respiratory illnesses from 
the time of birth until the final visit.  

Details of IV fluids given during an MA-RTI will be collected and recorded in the CRF.
6.6. Dose Modification 
Dose modification is not applicable in this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Discontinuation of study intervention is not applicable in this study.
7.2. Participant Discontinuation/Withdrawal From the Study 
A maternal participant may withdraw from the study at any time at her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. An infant participant may withdraw from the study at 
any time at the request of his or her parent(s) and/or legal guardian(s) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.
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The participants, or, if appropriate, their parent(s) and/or legal guardian(s), should be
questioned regarding their reason for withdrawal. The participant will be permanently
discontinued from the study at that time.
If a maternal participant withdraws from the study, she may request destruction of any 
remaining samples taken and not tested, but data already generated from the samples will 
continue to be available and may be used to protect the integrity of existing analyses. If an 
infant participant is withdrawn from the study, his or her parent(s) and/or legal guardian(s) 
may request destruction of any remaining samples, but data already generated from the 
samples will continue to be available, and may be used to protect the integrity of existing 
analyses. The investigator must document any such requests in the site study records and 
notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
Participants who withdraw after randomization will not be replaced.
7.3. Withdrawal of Consent 
Maternal participants and parent(s)/legal guardian(s) of infant participants born to maternal 
participants who request to withdraw consent from any further study contact or with persons 
previously authorized by the participant to provide this information should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible.  The withdrawal of consent should be explained in detail in the medical records by 
the investigator, as to whether the withdrawal is only from study procedures and/or 
postvaccination study follow-up. If the participant (maternal or infant) only withdraws from 
a study procedure, safety information should be completed until the end of the study, unless 
consent for further contact has been withdrawn.  In the event that vital status (whether the 
participant is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
The regulatory and ethical considerations for this study, including the informed consent 
process, are summarized in Section 10.1.1 and Section 10.1.3.
7.4. Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
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The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant, or parent(s) and/or legal guardian(s), and 
reschedule the missed visit as soon as possible and counsel the participant or parent(s) 
and/or legal guardian(s) on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or parent(s) and/or legal guardian(s) wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record.

Should the participant or parent(s) and/or legal guardian(s) continue to be 
unreachable, the participant will be considered to have withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the maternal participant’s routine clinical 
management and obtained before signing of the ICD may be utilized for baseline 
purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA and protocol.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
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circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
8.1. Efficacy Assessments
8.1.1. Efficacy Assessments – Infant Participants
MA-RTIs in the infant participant will be identified from birth until the end of the infant’s 
participation in the study.  If the infant participant meets any RTI criteria listed below that 
require a visit by or a visit to a healthcare provider (outpatient or inpatient visit, emergency 
room, urgent care, or scheduled home visit), an RTI study visit by the study staff will be 
required (see Section 8.11.7).
The RTI criteria are if the infant experiences 1 or more of the following respiratory signs or 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any duration

Cough

Inability to feed for any duration due to respiratory symptoms

Apnea

Any other respiratory symptom of concern 
Evaluation of these MA-RTI events will be based on predefined clinical signs and symptoms 
and testing criteria (shown in Table 1) obtained at the medically attended visit with the 
healthcare provider and/or the study visit. These events will be assessed and confirmed to be 
contributing to the study endpoints by an independent EAC as per the protocol.
8.1.1.1. Midturbinate Nasal Swab Collection and Testing Requirements for Endpoint 
Confirmation – Infant Participants
Midturbinate nasal swabs will be collected for RSV analyses from infant participants at each 
RTI study visit during the RSV surveillance period from birth until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). The swabs
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will be sent to Pfizer for centralized reverse transcription–polymerase chain reaction 
(RT-PCR) testing.
RSV testing performed locally as part of routine care will be considered valid when analyzed 
under the following conditions:  

Nucleic acid amplification technology (NAAT)-based test result positive for RSV was 
obtained using a Food and Drug Administration (FDA)-cleared assay.
AND

NAAT-based test result was obtained in a laboratory that is currently Clinical Laboratory 
Improvement Amendments (CLIA)-certified or has the equivalent US 
certification/accreditation (eg, College of American Pathologists [CAP]) or the equivalent 
ex-US certification as outlined in the adjudication charter. 
Note: Rapid antigen-based test results will not be considered for endpoint assessment.
Study samples should be collected as close to the medical visit as possible and preferably 
within 72 hours of the MA-RTI visit. Study samples positive for RSV by RT-PCR as 
defined above will count toward the endpoint definition when collected for up to 10 days 
after the MA-RTI, where Day 1 is the day of the MA-RTI visit. These results will be used 
for MA-RTI endpoint definition and confirmation as detailed in Table 1.
8.1.1.2. Events for Adjudication and Submission Guidance – Infant Participants
To maintain scientific integrity, this protocol will use an EAC for the adjudication of all 
efficacy endpoints as summarized below.  The EAC will remain blinded to the maternal 
participants’ vaccine assignments, and the EAC’s assessment of these events will represent 
the final confirmed endpoint classification of the event. 
The efficacy-related events for adjudication include all MA-RTI events. The study 
definitions for endpoint events and the MA-RTI adjudication criteria for the EAC, including 
roles and responsibilities, are specified in the endpoint adjudication committee charter 
(EACC). 
The identification of an MA-RTI will be made by the investigational site and communicated 
to Pfizer or its designee. However, these MA-RTI events may also be identified by Pfizer or 
its designee during the review of clinical data listings or by site monitors during routine 
monitoring of the infant participants’ study records. Pfizer or its designee will notify the 
investigational site of any events identified during this process.
The EAC is responsible for adjudicating whether MA-RTI events fulfill the protocol-defined 
clinical criteria as a primary endpoint, whether the event was due to RSV based on 
confirmatory testing, and the severity of the illness (eg, MA-RTI, MA-LRTI, or severe 
MA-LRTI).  The EAC will adjudicate all RSV-positive MA-RTI cases through the active 
follow-up period including all cases occurring up to 180 days after birth. The EAC will 
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adjudicate severe manifestations of RSV: all RSV-associated cases of hospitalization and 
severe MA-LRTI. All deaths during the study are to be reported to Pfizer Safety upon 
awareness. 
The Pfizer study team or designee will provide a listing of specific documents needed to 
support endpoint adjudication by the EAC. These documents will be detailed in the EACC
and the ISF.  Obtaining and submitting the documentation, including results of local testing 
for RSV, will be the responsibility of the investigational site. Documentation will vary based 
on the potential endpoint requiring adjudication and may include (but not be limited to) 
emergency room visit records, hospital discharge summaries, clinic and/or progress notes, 
diagnostic tests, pathology reports, autopsy reports, and death certificate information, as 
applicable.
Pfizer may request that additional cases of interest be reported to the committee in addition to 
those listed above, including cases in which RSV testing is indeterminant or otherwise 
unclear. Cases that are determined to be RSV positive using non–NAAT-based clinical 
testing can be adjudicated, explored, and summarized descriptively.
8.1.2. Exploratory Efficacy Assessments – Maternal Participants
An MA-RTI will be identified from vaccination until the end of the study and will contribute 
to an exploratory endpoint for maternal participants.  The definition and assessment criteria 
as described in Section 8.10.6 include a visit by or to a healthcare provider (outpatient or 
inpatient visit, emergency room, urgent care, or home visit) for any symptoms in the RTI 
criteria as detailed in Table 2.
The maternal participant should contact the study staff immediately but no later than the next 
scheduled visit to report RTI signs and symptoms for which she sought medical attention. 
The procedures as detailed in Section 1.2.3.1 and Section 8.10.6 will be required to capture 
the event in the CRF.
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal and Infant 
Participants
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition for 
infant participants should not be recorded as AEs. These data will be captured as efficacy 
assessment data only, as these are expected endpoints.  
For maternal participants, MA-RTI events that are consistent with the clinical and endpoint 
definition will be captured as detailed in Section 8.1.2 and will not be recorded as AEs.  
Any SAE that the investigator has judged to have a causal relationship with the 
investigational product MUST be reported to Pfizer Safety as described in Appendix 2, 
even if that event is a component of an endpoint.
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8.1.4. Immunogenicity Assessments 
8.1.4.1. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be approximately 30 mL (~15 mL/visit).  
8.1.4.2. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical 
Consideration for Clinical Trials Performed in Children.31
All infants will have a cord blood sample collected at birth. The cord blood is collected from 
the umbilical cord vein attached to the placenta after the umbilical cord has been clamped 
and cut. Blood should be collected as soon as feasible after birth to minimize coagulation 
and maximize volume. The total volume of cord blood to be collected for antibody 
assessment in this study will be 10 mL. 
If cord blood is unavailable, a blood sample may be collected from the infant participant up 
to 7 days after birth but preferably within 24 hours after birth.  The infant’s weight must 
be used to determine the volume of blood that can be collected (see Table 3).  
A blood sample will be collected from the infant participant only if a cord sample is not
obtained. In the event that a sample is collected, the volume of blood will vary depending on 
the infant’s weight. 
The maximum volume of blood collected from the infant in the absence of cord blood will be 
no more than 5 mL.
Table 3.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained
Body Weight (in kg)
Approximate Volume of Blood (in mL) 
to Be Collected 
<1.3
No blood draw
1.3 to ≤2.4
1.0
>2.4 to ≤3.7
2.0
>3.7 to ≤4.9
3.0
>4.9 to ≤6.2
4.0
>6.2
5.0
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant Participants
Maternal sera (prevaccination/time of delivery) and infant cord blood collected will be 
assayed for RSV A and RSV B serum neutralizing titers and anti-RSV prefusion F IgG 
levels. Maternal sera collected may be tested for Ig levels against nonvaccine RSV antigens
to assess natural RSV exposure.
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RSV A and RSV B serum neutralizing titers will be determined and reported as the 
neutralizing titer. IgG levels will be determined against both RSV A and RSV B prefusion F 
antigens in a direct-binding Luminex immunoassay (dLIA) and reported as an anti–
prefusion F IgG level.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development – Maternal and Infant Participants
Samples remaining after completion of the planned assays from blood draws or respiratory 
nasal swab specimens taken throughout the study may be used for additional vaccine and 
infectious disease related research. Samples may also be used for assay development, 
standardization, qualification, and validation.  This work is critical in the development, 
qualification, and validation of serological assays and is required by regulatory authorities for 
their use in the licensure of a vaccine.
8.1.4.5. Respiratory Pathogens – Infant Participants
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI
visit during the RSV surveillance period from birth until Visit 3, and for all hospitalizations 
due to an RTI and severe cases of MA-LRTI during the RTI surveillance period from Visit 
3 until the end of the study (see Section 1.2.4.1 and Table 1). 
Samples will be analyzed for RSV A, RSV B, and other respiratory pathogens by polymerase 
chain reaction (PCR)-based assays at a central laboratory. Additional exploratory analyses 
may also be performed.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.6. Biological Samples – Maternal and Infant Participants
Samples will be used only for scientific research.  Each sample will be labeled with a code so 
that the laboratory personnel testing the samples will not know the maternal or infant
participant’s identity.  Samples that remain after performing assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.  If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No sequencing of the maternal or infant participant’s DNA will be performed. 
The maternal participant may request that her (or her infant’s) samples, if still identifiable, be 
destroyed at any time; however, any data already collected from those samples will still be 
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used for this research.  The biological samples may be shared with other researchers as long 
as confidentiality is maintained, and no testing of the maternal and infant participant’s DNA 
is performed.
8.2. Safety Assessments 
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
Safety parameters will be assessed as described in the SoA and below for both maternal and 
infant participants.
8.2.1. Participant Electronic Diary – Maternal Participants
All maternal participants vaccinated in the study will be observed for at least 30 minutes after 
investigational product administration for any acute reactions. For all maternal participants, 
prespecified local reactions and systemic events will be collected for 7 days after vaccination.  
Maternal participants will be required to use an electronic diary (e-diary), installed on a 
provisioned device or as an application on a personal device, and will be asked to monitor 
and record local reactions, systemic events, and temperature each evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  Prior 
to vaccination, a baseline assessment of prespecified systemic events will be recorded in the 
e-diary.
The e-diary allows recording of these assessments only within a fixed time window each day, 
thus providing the accurate representation of the maternal participant’s experience at that 
time.
Similarly, based on local practice in certain countries/locales, a field worker may visit 
maternal participants in their homes daily after vaccination to assess and record local 
reactions, systemic events, and temperature each day (beginning in the morning) for 6 days 
following vaccination (Day 2 through Day 7, where Day 1 is the day of vaccination).  The 
field worker will be required to record these data on a provisioned device or an application 
on a personal device, thus providing the accurate representation of the maternal participant’s 
experience at that time.  For events persisting at Day 7 and use of antipyretic medication 
continuing at Day 7, the field worker will continue to visit the participant and record 
information until resolution.
Data on local reactions, systemic events, and temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via an internet-based 
portal.  At intervals agreed to by the vendor and Pfizer, these data will be transferred 
electronically to Pfizer for analysis and reporting.  These data do not need to be recorded by 
the investigator in the CRF, except the following conditions:
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
If a maternal participant withdraws because of prompted events recorded in the e-diary, 
the event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF. 
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate maternal participant compliance and as part of the 
ongoing safety review. These prospectively collected occurrences of local reactions and 
systemic events are graded as described in Section 8.2.1.1 and Section 8.2.1.2.
8.2.1.1. Local Reactions – Maternal Participants
Following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), the 
maternal participants/field worker will be asked to assess redness, swelling, and pain at the 
injection site and to record the symptoms in the e-diary or appropriate device, in the evening
or daily based on local practice.  
Redness and swelling will be measured by the maternal participant/field worker and recorded
in measuring device units (range: 1 to 20 and 21+) and then categorized during analysis as 
mild, moderate, or severe based on the grading scale in Table 4. Measuring device units can 
be converted to centimeters according to the following scale: 1 measuring device unit = 
0.5 cm.
A maternal participant with severe redness, swelling, or pain at the injection site will be 
prompted to contact the investigator to perform an unscheduled visit to assess the reaction or 
will be referred to the appropriate healthcare facility at the discretion of the field worker if 
there are any concerns, as appropriate.  In the event that the maternal participant does not 
call, the investigator or qualified designee will contact the maternal participant.
Only an investigator or a qualified designee is able to classify a maternal participant’s local 
reaction as Grade 4, after clinical evaluation of the maternal participant or documentation 
from another medically qualified source (eg, emergency room or hospital record) or, in the 
case of pain at the injection site only, contact with the maternal participant.  If a maternal 
participant experiences a Grade 4 local reaction, the investigator must immediately notify the 
sponsor.  A Grade 4 reaction will be collected as an AE on the CRF.  The event will be 
graded using the AE intensity grading scale (Section 10.2.4).
The site staff/field worker will educate the maternal participant regarding signs and 
symptoms that would prompt site contact.  
If a local reaction persists beyond the end of the e-diary period, the maternal participant will 
be requested to report that information and/or any new AEs that develop to the investigator,
or the field worker will continue to visit the maternal participant to assess and record the 
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information until resolution, as per local practice. The investigator will enter this additional 
information in the maternal participant’s source notes and CRF.
Table 4.
Grading Scale for Local Reactions
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 
20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 
20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis
Pain (at the 
injection site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a maternal participant’s local reaction as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
contact with the maternal participant.  Grade 4 local reactions will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.1.2. Systemic Events – Maternal Participants
Prior to vaccination on Day 1, a baseline assessment of fatigue, headache, vomiting, 
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e-diary. Following 
vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), maternal 
participants will be asked to assess fatigue, headache, vomiting, nausea, diarrhea, muscle 
pain, and joint pain and to record the symptoms in the e-diary in the evening or, based on 
local practice in certain countries/locales, a field worker will visit maternal participants daily 
after vaccination to assess the presence of systemic events each day (beginning in the 
morning) for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination).  The field worker will record the symptoms in the e-diary daily. The symptoms 
will be assessed by the maternal participant according to the grading scale in Table 5.  
Maternal participants will also be instructed to contact site staff if they visit the emergency 
room or are hospitalized for severe fatigue, headache, vomiting, nausea, diarrhea, muscle 
pain, or joint pain within 7 days after vaccination. Based on local practice in certain 
countries/locales, maternal participants will be referred to the appropriate healthcare facility 
at the discretion of the field worker if there are any concerns, as appropriate. In the event 
that the maternal participant does not call, the investigator or qualified designee will contact 
the maternal participant. The study staff/field worker may also contact the maternal 
participant to obtain additional information on events entered into the e-diary.
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Only an investigator or qualified designee is able to classify a maternal participant’s systemic 
event as Grade 4, after clinical evaluation of the maternal participant or documentation from 
another medically qualified source (eg, emergency room or hospital record) or contact with 
the maternal participant.  If a maternal participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.  Grade 4 reactions will be collected as an 
AE on the CRF.  The event will be graded using the AE intensity grading scale 
(Section 10.2.4).
Further, if a systemic event persists beyond the end of the e-diary period, the maternal 
participant will be requested to report that information and/or any new AEs that develop to 
the investigator, or the field worker will continue to visit the maternal participant to assess 
and record the information until resolution, as per local practice. The investigator will enter 
this additional information in the maternal participant’s source notes and CRF.
Table 5.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness in 
diaries)
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Headache
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Vomiting
1 to 2 times in 24 hours
>2 times 
in 24 hours
Requires 
intravenous 
hydration
Emergency room 
visit 
or hospitalization 
for severe 
vomiting
Nausea
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe nausea
Diarrhea
2 to 3 loose stools
in 24 hours
4 to 5 loose stools
in 24 hours
6 or more loose 
stools
in 24 hours
Emergency room 
visit
or hospitalization 
for severe diarrhea
Muscle pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe muscle pain
Joint pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe joint pain
a.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic event as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the maternal participant.  Grade 
4 systemic reactions will be collected on the AE case report form and assessed by the investigator using 
the AE intensity grading scale as detailed in Section 10.2.4.
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8.2.1.3. Temperature – Maternal Participants
A digital thermometer will be given to the maternal participant with instructions on how to 
measure oral temperature at home.  Temperature will be collected in the evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination) and at 
any time during the 7 days following vaccination that fever is suspected. Similarly, based on 
local practice in certain countries/locales, the field worker will visit maternal participants 
daily for 7 days after vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination) to collect the temperature.
Fever is defined as an oral temperature of ≥100.4°F (≥38.0°C). The highest temperature for 
each day will be recorded in the e-diary, where possible. In certain countries/locales, if a 
temperature of ≥100.4°F (≥38.0°C) is recorded for a maternal participant during the 
collection of diary events after vaccination, the field worker will perform a rapid test for 
malaria as per local practice.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature less than 100.4°F [38.0°C]) in order to 
collect a stop date in the CRF. 
A maternal participant with a fever >102.0F (>38.9°C) will be prompted to contact the 
investigator. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the field worker if there 
are any concerns, as applicable. In the event that the maternal participant does not call, the 
investigator or qualified designee will contact the maternal participant.  The investigator or 
qualified designee will assess the fever and perform an unscheduled visit as appropriate.
Temperature will be measured and recorded to 1 decimal place and then grouped into ranges 
for the analysis according to Table 6.  Temperatures reported in degrees Fahrenheit will be 
programmatically converted to degrees Celsius for reporting.
Table 6.
Ranges for Fever
Fever
≥38.0°C to 38.4°C
>38.4°C to 38.9°C
>38.9°C to 40.0°C
>40.0°C
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant Participants
There are no protocol-required laboratory assessments.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
AEs will be reported by the maternal participant/parent(s)/legal guardian(s).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
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meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7). 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
Maternal Participants
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each maternal participant including her fetus begins from the time the maternal 
participant provides informed consent, which is obtained before participation in the study 
(ie, before undergoing any study-related procedure and/or receiving investigational product), 
through and including a minimum of 28 calendar days after the last administration of the 
investigational product.
In this study, the investigator and site staff will ensure the active elicitation and collection of 
safety events as detailed below:

The active collection period for nonserious AEs begins once informed consent has been 
provided and continues through a minimum of 28 calendar days after vaccination.  

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

In addition, AEs occurring up to 48 hours after blood draws that are related to study 
procedures must be reported in the CRF.  

Details of any MA-RTI will not be collected as AEs/SAEs from informed consent until 
the maternal participant completes the study, unless the investigator or an appropriate 
designee deems the event to be possibly related to the investigational product. 
For maternal participants who are screen failures, the active collection period ends when 
screen failure status is determined.
Infant Participants
For the infant participant, the time period for actively eliciting and collecting safety events is 
detailed below:

The active collection period for nonserious AEs begins at birth and continues through and 
including a minimum of 28 calendar days after birth. 

The active collection period for NDCMCs and SAEs begins at birth and continues 
through the last study visit.  
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o
Details of any MA-RTI will not be collected as AEs/SAEs from informed consent 
until the infant participant completes the study, unless the investigator or an 
appropriate designee deems the event to be possibly related to the investigational 
product or if the event resulted in death. See Section 8.1 for the reporting 
procedures for efficacy-related endpoints. Note: Details of the MA-RTI visit 
should be recorded in the eCRF.

In addition, AEs occurring up to 48 hours after blood draws or nasal swabs that are 
related to study procedures must be reported in the CRF.  
For maternal participants, and parent(s)/legal guardian(s) of infant participants born to 
maternal participants, who withdraw from the study and withdraw consent for the collection 
of future information, the active collection period ends when consent is withdrawn. 
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the Vaccine SAE Reporting Form.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy; 
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those that occur within 1 month after birth; or congenital anomaly 
[in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.  In addition, infant deaths after 
1 month of age should be reported as SAEs. 
Further follow-up may be requested by the sponsor and will be handled on a case-by-case 
basis (eg, follow-up on preterm infants to identify developmental delays). 
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety. 
The same is applied for those SAEs after the active collection period has ended, should they 
occur to the fetus.  In addition, infant deaths that occur after 12 months of age should be 
reported as SAEs when the investigator believes the death has at least a reasonable possibility 
of being related to investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
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8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All AEs/SAEs occurring in a participant during the active collection period are recorded in 
the CRF.
The investigator obtains general information on the pregnancy and its outcome for all study 
participants.  The investigator will follow the pregnancy until completion (or until pregnancy 
termination).  In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth.  In the event of a termination, the reason(s) for termination should be 
specified and, if clinically possible, the structural integrity of the terminated fetus should be 
assessed by gross visual inspection (unless preprocedure test findings are conclusive for a 
congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, stillbirth, neonatal death,
defined as those deaths that occur within 1 month after birth; or congenital anomaly [in a 
live-born baby, a stillbirth, or a neonatal death]), the investigator should record this 
information in the CRF.  In addition, infant deaths after 1 month of age should be recorded in 
the CRF as SAEs. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.4).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 2.
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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
Potential efficacy endpoints on this study as defined in Section 8.1 will be excluded from the 
standard SAE reporting process unless deemed possibly related to investigational product.  
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the 
Investigational Product
8.3.5.1. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Scenarios of exposure during breastfeeding for infants not delivered during the study must be 
reported, irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours 
of the investigator’s awareness, using the Vaccine SAE Reporting Form.  An 
exposure-during-breastfeeding report is not created when a Pfizer drug specifically approved 
for use in breastfeeding women (eg, vitamins) is administered in accord with authorized use.  
However, if the infant experiences an SAE associated with such a drug’s administration, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.2. Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
investigational product, which may or may not lead to the occurrence of an AE. 
Note: This does NOT apply to maternal participants enrolled in this trial.
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In addition, the scenarios below describe environmental exposures that could lead to an 
exposure during pregnancy (EDP): 

A female becomes or is found to be pregnant, having been exposed (eg, because of 
environmental exposure) to the investigational product; or the female becomes or is 
found to be pregnant after being exposed to the investigational product;

A male has been exposed (eg, because of environmental exposure) to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy. 
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the Vaccine SAE Reporting Form and the Exposure During Pregnancy 
Supplemental Form, as applicable, regardless of whether there is an associated SAE.  In the 
event of an EDP, the information submitted should include the anticipated date of delivery.  
Since the information does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the ISF.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
are as follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.
8.3.6. Adverse Events of Special Interest
This section provides information on adverse events of special interest (AESIs) that may be 
detected during the study.
For infant participants:

Preterm birth (born at <37 weeks’ gestation)
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
Birth weight 1001 to 2500 g

Developmental delay
The following AESIs are to be reported as SAEs:

Extremely preterm birth (<28 weeks)

Extremely low birth weight (≤1000 g)
For maternal participants:

Preterm delivery with cause, if available
All AESIs must be reported as an AE or SAE following the procedures described in
Section 8.3.1 through Section 8.3.4. An AESI is to be recorded as an AE or SAE on the 
CRF. In addition, an AESI that is also an SAE must be reported using the Vaccine SAE 
Reporting Form.
8.3.7. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices.
The definition of a medical device deficiency can be found in Appendix 4.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 2 of the protocol.
8.3.7.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 4.
8.3.7.2. Follow-up of Medical Device Deficiencies
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  Follow-up applies to all participants, including 
those who discontinue study intervention.
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The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.7.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
Information will be provided to the sponsor as described in the IP manual. 
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 
Section 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.7.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
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8.3.8. Medication Errors 
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.  
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration by an incorrect route;

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
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8.4. Treatment of Overdose
For this study, any additional dose of investigational product will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose in the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
No interruptions or dose modifications will be made in this study. 
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Health Economics
Health economics will be evaluated in exploratory analyses assessing vaccine impact on 
healthcare resource utilization parameters evaluated during study visits, which may include 
the following: number and type of medical visits, length of hospital stay, requirement for 
mechanical ventilation, requirement for respiratory diagnostic procedures, requirement for IV 
fluids, requirement for prescriptions, and antibiotic use. 
8.10. Procedures – Maternal Participants 
8.10.1. Screening and Vaccination Visit (Clinic; Day -28 to Day 1 – Visit 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant. Each signature on the 
ICD must be personally dated by the signatory.  
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Maternal participants who might be illiterate must thumbprint the ICD and it must be signed 
and dated by an impartial witness who was present throughout the entire informed consent 
process before performing any study-related procedures.
The investigator or his or her designee will also sign and date the ICD.  A copy of the 
signed/thumbprinted and dated ICD must be given to the maternal participant.  The source 
data must reflect that the informed consent was obtained before participation in the 
study.
If the maternal participant is found ineligible for the study based on a full assessment of 
inclusion and exclusion criteria, the investigator may advise the participant, either by 
telephone or face to face, that the participant will be excluded from further participation in 
the study, as defined in Section 5.4.  All eligible maternal participants will proceed to 
complete the vaccination visit.
Standard-of-care procedures performed prior to informed consent can be considered for use 
in the study provided they are performed in close proximity (approximately up to 28 days) to 
the timing of vaccination and follow guidance around the timing of procedures stipulated in 
the protocol.
In countries/locales where procedures to confirm maternal participant eligibility for
this clinical trial are not routinely performed, the procedures must be obtained and 
reviewed by the investigator or qualified designee up to 28 days prior to vaccination.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.
The following procedures will be performed:

Obtain written informed consent from the maternal participant before performing any 
study-specific procedures. If the maternal participant is illiterate, she must thumbprint 
the ICD and it must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity).  The date of birth will be 
collected to critically evaluate the immune response and safety profile by age.

Obtain and record current alcohol, tobacco, marijuana, or any illicit drug usage.

Obtain and record any medical, surgical, and obstetric history of clinical significance 
including history from prior and current pregnancy(ies).  

Record the LMP and estimated delivery date (EDD).
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
Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.

Record the prepregnancy BMI in the source documentation. If the prepregnancy BMI is 
not available, record the BMI at the time of the first obstetric visit during the current 
pregnancy. 

Perform targeted physical examination evaluating/noting any clinically significant 
abnormalities within the following body systems: general appearance; skin; head, eyes, 
ears, nose, and throat; heart; lungs; abdomen; musculoskeletal; extremities; neurological; 
and lymph nodes.  Significant medical and surgical history and abnormal observations 
from the physical examination will be documented and recorded in the CRF. 

Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement.
o
Where an obstetric ultrasound examination is not performed at ≥18 weeks of 
pregnancy as part of prenatal standard of care, perform an ultrasound examination.
o
Note: Physical or obstetric examinations performed as standard of care may be 
admissible if performed within 7 days prior to the vaccination visit.

Obtain details of any Ig (including monoclonal antibodies or immune globulin [Rho(D)
immune globulin, eg, RhoGAM]) or blood products (eg, whole blood, packed cells) given 
at any time during the current pregnancy.

Obtain details of any nonstudy vaccinations given at any time during the current 
pregnancy.

Obtain details of syphilis, HIV, and HBV status.  

Note: Only participants with a documented negative syphilis test result and negative 
HIV antibody and HBV surface antigen test results obtained during the current 
pregnancy are eligible for randomization. 

If not performed as standard of care, assessment should be performed as part of the 
study, locally, and vaccination of maternal participant should be deferred until the 
results are available and confirmed to be negative within 28 days prior to study 
randomization. 

Ensure and document that all the inclusion criteria and none of the exclusion 
criteria are met.

Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.2.3.

Issue the maternal participant an e-diary and provide instructions on its completion.
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
Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures, and provide instructions on their use.

Obtain and record baseline assessment of systemic events prior to vaccination in the 
maternal participant’s source documents. Ask the maternal participant to capture the 
corresponding baseline systemic event measurements in her e-diary.

Prior to vaccination, collect a blood sample of approximately 15 mL for serologic 
assessments (prevaccination blood collection should take place on the same day or within 
7 days before the vaccination visit).

Obtain the maternal participant’s randomization number and investigational product kit 
number using the IRT system. Refer to the IRT manual for further instructions on this 
process.  

Qualified site staff member(s) will administer a single-vial dose of investigational 
product into the deltoid muscle of the (preferably) nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
Please refer to the IP manual for further instruction on this procedure.

Site staff must observe the maternal participant for any acute reactions for at least 
30 minutes after investigational product administration.  

Record any acute reactions in the maternal participant’s source documents, on the AE 
page of the CRF, and on the Vaccine SAE Reporting Form as applicable.

Ask the maternal participant to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination, OR explain to the maternal participant that a field worker 
will visit her every day from Day 2 to Day 7 after vaccination (where Day 1 is the day of 
vaccination) to take her temperature and record systemic events, acute local reactions, 
and use of antipyretic medication in a diary (if applicable).

Ask the maternal participant to contact the site staff or investigator immediately if she 
experiences any of the following from Day 1 to Day 7 after vaccination to determine if an 
unscheduled reactogenicity visit is required as detailed in Section 8.10.5 OR inform the 
maternal participant that if she experiences any of the following from Day 1 to Day 7 
after vaccination or is taking antipyretic medication at Day 7, then the field worker will 
continue to visit until resolution.  Furthermore, the maternal participant will be referred to 
the appropriate healthcare facility at the discretion of a field worker if there are any 
concerns as detailed in Section 8.10.5.

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring >20 measuring device units 
(greater than 10 cm).
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
Severe pain at the injection site.

Any severe systemic event.

Inform the maternal participants that if a temperature of ≥100.4°F (≥38.0°C) is recorded 
during the collection of diary data, she will be required to have a rapid test for malaria as 
per local practice and details will be recorded in the diary (if applicable, based on local 
practice).

Remind maternal participants that study staff may contact them to obtain additional 
information on events entered into the e-diary.

Remind maternal participants to inform the study staff of any AEs and SAEs that occur 
for the duration of the trial as described in Section 8.2 and Section 10.2.

Remind the maternal participant to bring the completed e-diary to the next visit
(if applicable). 

Complete the source documents.

The investigator or an authorized designee completes the CRFs and the blinded 
dispenser/administrator completes the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.  

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6. 

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit (The field worker will contact the maternal participant prior to the next 
study visit to remind her, if applicable).
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8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After Vaccination) 
If delivery occurs before this visit, this visit will not be conducted.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

Review the participant’s e-diary data. Collect stop dates of any e-diary events ongoing 
on the last day that the e-diary was completed and record stop dates in the CRF.

Record details of any MA-RTI, including the diagnosis. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2. Note: Active 
elicitation and collection of AEs and SAEs through 28 days after vaccination must occur 
even if delivery occurs within 28 days after vaccination.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6. 

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit (The field worker will contact the maternal participant prior to the next 
study visit to remind her, if applicable).
8.10.3. Delivery (Maternity Unit)
The delivery visit spans the time from when a participant is admitted in labor through 
discharge following delivery of her infant. Protocol-specified procedures associated with 
this delivery visit may be done at any time during this period.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.
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
If available, record the maternal participant’s group B streptococcal (GBS) status and if 
any medication was given for intrapartum antibiotic prophylaxis (IAP).

Record details of any nonstudy vaccinations given since the last visit.

Collect a blood sample of approximately 15 mL for serologic assessments.  Note:  The 
maternal participant’s blood sample can be taken at any time during the delivery visit, 
preferably before delivery. In the event that the blood sample cannot be obtained 
before delivery, the sample should be collected as close to delivery as possible and at 
most 48 hours postpartum.
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments 
must also be collected.  Cord blood is collected from the umbilical cord vein attached to 
the placenta prior to the blood clotting within the cord and after the umbilical cord has 
been clamped and cut.  This sample should be labeled with the infant’s participant ID 
number.

Record pregnancy outcome information, including vital status of the infant (live, 
stillbirth, or termination), mode of delivery (vaginal delivery, cesarean section, etc), and 
the use of any assisted devices (forceps or vacuum).  

Record details of any MA-RTI, including the diagnosis. 

Record AEs as described in Section 8.2 and Section 10.2.

Ask the maternal participants to contact the site to report any significant illness (new or 
worsening), any medically attended respiratory events (eg, doctor’s visit, emergency 
room visit), or any hospitalization that occurs during the study period as detailed in 
Section 8.10.6.

Ask the maternal participant to contact the site staff or investigator if her newborn infant 
meets the MA-RTI study criteria OR the field worker will contact the maternal 
participant/legal guardian(s) weekly to remind them to report any MA-RTI (if 
applicable).

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.10.4. 6-Month-Postdelivery Visit (Clinic or Telephone; 180 to 210 Days After 
Delivery)

Obtain details of any postnatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [eg, HBIG]) or Rho(D) immune globulin [eg, RhoGAM]) or blood 
products (eg, whole blood, packed cells) given since the last visit.

Record details of any nonstudy vaccinations given since the last visit.

Record details of any MA-RTI, including the diagnosis.

Ask the maternal participant to contact the site staff or investigator if her infant meets the 
MA-RTI study criteria OR the field worker will contact the maternal participant/legal 
guardian(s) weekly to remind them to report any MA-RTI, if applicable.

Record AEs as described in Section 8.2 and Section 10.2.

Complete the maternal participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.5. Unscheduled Reactogenicity Visits 
If the maternal participant reports 1 or more of the following, a contact must occur as soon as 
possible between the maternal participant and the investigator, or a medically qualified 
member of the study site staff, to assess if an unscheduled reactogenicity visit is required OR
based on local practice in certain countries/locales, maternal participants will be referred to 
the appropriate healthcare facility at the discretion of the field worker if there are any 
concerns regarding reactogenicity events, including:

redness at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

swelling at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

severe injection site pain on the arm that the investigational product was 
administered, 

fever ≥39.0°C (≥102.1°F).
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The maternal participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or
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
The participant/field worker recorded an incorrect value in the e-diary (confirmation 
of an e-diary data entry error), or

The investigator or appropriate designee determines that the visit is not required.
This contact will be recorded in the maternal participant’s source notes and in the CRF.
Any ongoing reactions must be assessed at the next scheduled visit.
The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure oral temperature.

Measure the participant’s heart rate.

Measure the participant’s blood pressure (seated).

Measure the minimum and maximum diameters of redness (if present) on the arm in 
which the investigational product was administered.

Measure the minimum and maximum diameters of swelling (if present) on the arm in 
which the investigational product was administered.

Assess if necrosis is present at the injection site on the arm in which the investigational 
product was administered.

Assess if any exfoliative dermatitis is present.

Assess any injection site pain on the arm in which the investigational product was 
administered that is present in accordance with the reactogenicity grading scale provided 
in Section 8.2.1.1.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 8.2.1.2.

Ask the participant if she attended an emergency room visit or was hospitalized.

For severe pain at the injection site resulting in an emergency room visit or 
hospitalization, severe systemic events associated with an emergency room visit or 
hospitalization, any necrosis on the arm in which the investigational product was 
administered, or exfoliative dermatitis, the investigator or qualified designee must assess 
these events in accordance with the intensity AE grading scale provided in
Section 8.2.1.1 and Section 8.2.1.2.
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
Record AEs and SAEs as described in Section 8.2 and Section 10.2.

Complete the participant’s source documents.

The investigator or an authorized designee will complete the CRFs.
The study staff/field worker may contact the participant to obtain additional information on 
events entered into the e-diary, as appropriate.
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria – Maternal 
Participants

Starting from Day 1 after vaccination (where Day 1 is the day of vaccination) until the 
end of the study, all maternal participants will be monitored for MA-RTIs as detailed in 
Section 1.2.3.1 and Section 8.1.2. Maternal participants should notify the site and/field 
worker of the occurrence of any MA-RTIs immediately but no later than the next study 
visit. Note: Site contact may be by an electronic method of communication (including 
but not limited to electronic messaging, short message service [SMS], text, email), by 
phone call, or by face-to-face contact.

The definition of maternal RTI includes 1 or more of the following signs and/or 
symptoms:
o
New or increased sore throat
o
New or increased cough
o
New or increased nasal congestion
o
New or increased nasal discharge
o
New or increased wheezing
o
New or increased sputum production
o
New or increased shortness of breath

Record the details of any MA-RTI, including the diagnosis, the medically attended visit 
location (hospital, outpatient visit, emergency room, urgent care, or home visit), duration 
of hospitalization, intensive care unit (ICU) duration if applicable, prescribed medications 
for the MA-RTI, assessments including RSV test result (eg, NAAT, rapid antigen 
detection tests, or any other molecular diagnostic test), if available, and the final 
diagnosis.

Record the details of any nonstudy vaccinations.

Record AEs as described in Section 8.2 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.
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
Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11. Procedures – Infant Participants
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After Birth)

Manually assign a single infant participant identifier using the IRT system (or 
equivalent).

Collect a cord blood sample of approximately 10 mL for immunogenicity assessments.  
Cord blood is collected from the umbilical cord vein attached to the placenta prior to the 
blood clotting within the cord and after the umbilical cord has been clamped and cut.  
This sample should be labeled with the infant’s participant ID number.

If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 24 hours, but up to 7 days after birth.  The volume of blood collected 
will be based on the weight of the infant (refer to Table 3).

Ensure and document that all the infant inclusion criteria and none of the infant exclusion 
criteria are met.

Collect demography (including complete date of birth [ie, dd-Mmm-YYYY], sex, race, 
and ethnicity).  The date of birth will be collected to critically evaluate the immune 
response.

Obtain and record the infant’s length, head circumference, and weight at birth.

Obtain and record the infant’s birth data, including GA and appearance, pulse, 
grimace, activity, and respiration (Apgar) score. 

Obtain and record background factors as described in Section 10.5.

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.

Standard-of-care vital signs and examination procedures can be considered for use in 
the study provided they were performed within 48 hours after birth. Note: Please 
reference the physical examination procedures below for details. 

Perform a physical examination, if not performed as part of standard of care, noting 
any clinically significant abnormalities within the following body systems: general 
appearance; skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; back; 
musculoskeletal; extremities; genitourinary; neurological; and lymph nodes.  
Abnormal results must be recorded on source documents as well as the physical 
examination pages of the CRF; only if the abnormal finding is deemed to be clinically 
significant should this be recorded on the AE pages of the CRF. 
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
Record details of any congenital anomalies on the AE page of the CRF, and report 
as an SAE as described in Section 10.2.3.

Record any medication as described in Section 6.5.5.

Obtain details of any Ig (including monoclonal antibodies [eg, Synagis] or immune 
globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given to the 
infant participant since birth.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Review the weekly contact schedule with the parent(s)/legal guardian(s) and collect 
contact information OR remind the parent(s)/legal guardian(s) that a field worker will 
contact them weekly to remind them to report any MA-RTI (if applicable).

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria. An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11.2. Visit 2 – 1-Month Follow-up (Clinic, 28 to 48 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.

Standard-of-care vital signs and examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit. Note: Please 
reference the physical examination procedures below for reporting details. 

Perform an examination, if not performed as part of standard of care, noting any 
clinically significant abnormalities in the site source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.
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
Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee 
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria.  An RTI study visit, along with a nasal swab collection, must be 
performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every 7 days 
from birth until the 6-month follow-up visit to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The weekly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.7.1 for guidance on reported cases of 
MA-RTIs in infant participants during the first 6 months after birth. 
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic, 180 to 210 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 

Standard-of-care vital signs and examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit. Note: Please 
reference the physical examination procedures below for reporting details. 

Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities in the source documents. Newly identified 
abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF.

Record details of any newly emergent congenital anomalies on the AE page of the 
CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 
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
Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of MA-
RTIs in infant participants. 

Ask the parent(s)/legal guardian(s) to contact the investigator immediately if any 
significant illness or hospitalization occurs or if the infant meets the MA-RTI visit
criteria.  An RTI study visit, along with a nasal swab collection, must be performed 
for all hospitalizations due to an RTI and severe MA-LRTIs as described in 
Section 1.2.4.1 and Section 8.11.8.
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if
a clinic visit is conducted). 

Standard-of-care vital signs and examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit. Note: Please 
reference the physical examination procedures below for details.

Perform a targeted physical examination, if not performed as part of routine care as 
described above, noting any clinically significant abnormalities in the source documents. 
Newly identified abnormal findings must be recorded on source documents and, if 
considered clinically significant in the judgment of the investigator/examiner, on the AE 
page of the CRF. Only applicable if a clinic visit is conducted.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies. 
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
Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants except for infant participants born during the first year of the study.

The investigator or an authorized designee completes the CRF for infant participants born 
during the first year of the study. Note: An additional 12-month blinded follow-up period 
for longer-term RTI surveillance and safety oversight will be included for these 
participants.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Confirm the understanding of the infant participant’s parent(s)/legal guardian(s) 
regarding site contact for the study, which is approximately every month (28 to 35 days) 
until the end-of-study visit. Ask the parent(s)/legal guardian(s) to contact the 
investigational site/field worker promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.
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8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days After Birth; 
Infant Participants Born During the First Year of the Study Only)

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI visit criteria.  
The monthly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.8 for guidance on reported cases of 
MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI visit criteria.  
An RTI study visit, along with a nasal swab collection, must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 742 Days After 
Birth; Infant Participants Born During the First Year of the Study)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if 
a clinic visit is conducted). 

Standard-of-care vital signs and examination procedures can be considered for use at this 
study visit, if they were performed within the window of the study visit. Note: Please 
reference the physical examination procedures below for reporting details. 

Perform a targeted physical examination, if not performed as part of routine care, noting 
any clinically significant abnormalities in the source documents . Newly identified 
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abnormal findings must be recorded on source documents and, if considered clinically 
significant in the judgment of the investigator/examiner, on the AE page of the CRF. 
Only applicable if a clinic visit is conducted.

Obtain and record details of any NDCMCs or newly emergent congenital anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents. 

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants born during the first year of the study.
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 Months After 
Delivery)

This is an active surveillance period spanning from birth through 6 months after delivery 
(Visit 3).

The sponsor may alter the frequency of the weekly contacts or the duration of 
surveillance for MA-RTI based on RSV surveillance data or other operational factors.
8.11.7.1. RTI Associated With a Medical Visit – Hospital, Home, or Clinic Visit

Contact the infant participant’s parent(s)/legal guardian(s) approximately every week 
(7 to 10 days) from birth until Visit 3 (6-month follow-up visit), to remind the 
parent(s)/legal guardian(s) to contact the investigational site promptly if the infant meets 
the criteria for an RTI-associated medical visit.  The weekly contact may be via the 
e-diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Table 1 regarding clinical signs 
and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an event requiring a visit to a healthcare provider, the site staff 
and/field worker should confirm, based on information provided, whether the event meets 
the criteria for an MA-RTI. Please refer to Table 1 and Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

When an infant MA-RTI criterion is met or confirmed, the site/field worker will obtain 
records from the medically attended visit and record the healthcare information as 
detailed in Appendix 6.
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
When an infant MA-RTI criterion is met or confirmed, the infant participant will be 
seen as soon as possible and within 72 hours (preferable) or up to 10 days for an RTI 
study visit by the investigational site staff or qualified designee. 

The infant participant may be seen either at the time of the MA-RTI, at home or at the 
study site (if discharged), or if the infant participant has been hospitalized or is receiving 
treatment at another medical facility, the site staff/field worker can conduct the RTI study 
visit at those facilities.  
o
If the RTI study visit is not performed within 72 hours of the event, it should still be 
performed, including the collection of nasal swab specimens. 
o
Targeted assessments at an RTI study visit include but are not limited to:
o
Respiratory signs: lower chest wall indrawing.
o
Vital sign assessment: respiratory rate, heart rate, and oxygen saturation by pulse 
oximetry.
o
Nasal swab collection from the infant participant for testing at the central 
laboratory.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site/field worker if the infant’s 
illness worsens, or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for the event as detailed in Section 8.1.
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit Criteria

This is a long-term surveillance procedure for all infant participants from 6 months after 
delivery (Visit 3) until the last study visit.  

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) from Visit 3 (6-month follow-up visit) until the end-of-study visit, to 
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remind the parent(s)/legal guardian(s) to contact the investigational site promptly if the 
infant meets the criteria for an MA-RTI visit.  The monthly contact may be via the e-
diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Section 8.1 regarding clinical signs 
and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an MA-RTI, the site should obtain additional information and 
determine whether the event also meets the study definition of a severe MA-LRTI. 
o
Note: Severe MA-LRTI is defined in Table 1.

The site/field worker will obtain records from the medically attended visit and record the 
healthcare information as detailed in Appendix 6.

When an infant MA-RTI criterion is confirmed and also meets the study definition of 
hospitalization due to an RTI or a severe MA-LRTI, the infant participant will be seen 
as soon as possible and within 72 hours (preferable) or up to 10 days for an RTI study 
visit that includes a nasal swab collection by the investigational site staff/field worker. 
The staff/field worker will obtain the nasal swab within 72 hours (preferable) or up to 
10 days of the event with the infant participant either at home (if discharged) or, if the 
infant participant has been hospitalized or receiving treatment at another medical facility, 
the site staff/field worker will conduct the visit at those facilities.  
o
Note: Nasal swab collection from the infant participant is for testing at the central 
laboratory.

A targeted RTI study visit will be required for all reported cases of hospitalization due to 
an RTI or severe MA-LRTI only, and this includes but is not limited to:
o
Respiratory signs: apnea, lower chest wall indrawing.
o
Vital sign assessment: respiratory rate, heart rate, and oxygen saturation by pulse 
oximetry.

A targeted RTI study visit is not required for an MA-RTI event not meeting the definition 
of hospitalization due to an RTI or severe MA-LRTI.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the MA-RTI event, including emergency room or
hospitalization details with admission and discharge date (if applicable).

Record any medication as described in Section 6.5.5.
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
Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.  Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site if the infant’s illness worsens, 
or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for hospitalizations due to an RTI and 
severe MA-LRTI events only as detailed in Section 8.1.
8.12. Communication and Use of Technology
In a study of this duration that is event-driven, it is vital to ensure that communication 
between the study site and the maternal participant and parent(s)/legal guardian(s) is 
maintained to ensure that endpoint events are not missed.  This study will employ various 
methods, tailored to the individual participant (maternal and/or infant participant), to ensure 
that communication is maintained and study information can be transmitted securely.  Using 
appropriate technology, a communication pathway between the maternal participant and 
parent(s)/legal guardian(s) and the study site staff will be established.  The maternal 
participant and the parent(s)/legal guardian(s) may be able to utilize their own devices to 
access this technology, or use a device provided by the sponsor.  Traditional methods of 
telephone communication will also be available. The technology solution may facilitate the 
following:

Contact with the investigator.

The ability of the maternal participant/parent(s)/legal guardian(s) to report MA-RTI visits
associated with the infant participant.

An alert in the event that the maternal or infant participant is hospitalized.

Visit reminders.

Messages of thanks and encouragement from the study team.

A platform for recording local reactions and systemic events (e-diary).
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9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Estimands and Statistical Hypotheses
The null hypothesis to be tested concerns VE for the primary endpoints. The RSV vaccine 
will be compared to placebo, testing the hypotheses H0: VE ≤20% vs Ha: VE 20%. For all 
secondary efficacy endpoints, the RSV vaccine will be compared to placebo, testing the 
hypotheses H0: VE 0% vs Ha: VE >0%. Hypothesis testing of the secondary endpoints is 
conditional upon rejection of the null hypothesis for at least 1 of the primary endpoints.
9.1.1. Estimands – Infant Participants
9.1.1.1. Efficacy
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with key protocol criteria (evaluable participants): 

VE, defined as the percentage relative risk reduction in the incidence of MA-LRTI due to 
RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of severe MA-LRTI 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of hospitalization 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of all-cause 
MA-LRTI in the RSV vaccine group, relative to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  For participants who 
discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.2. Immunogenicity
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with the key protocol criteria (evaluable participants):

Functional antibody levels estimated by the GMT for RSV A and RSV B serum
neutralizing titers.
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
Geometric mean ratio (GMR), estimated by the ratio of the GMTs for RSV A and RSV B
serum neutralizing titers of the RSV vaccine group to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as missing completely at random (MCAR) is assumed.  For participants 
who discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.3. Safety
In infant participants born to the maternal participants receiving 1 dose of investigational 
product:

The percentage of infant participants with specific birth outcomes.  

The percentage of infant participants having AEs from birth through 1 month of age.

The percentage of infant participants having SAEs, NDCMCs, and new diagnosed 
congenital anomalies from birth through the last study visit.
Missing AE dates and missing AE intensity will be handled according to Pfizer safety rules.
9.1.2. Estimands – Maternal Participants
9.1.2.1. Immunogenicity
In maternal participants receiving 1 dose of investigational product and in compliance with 
the key protocol criteria (evaluable participants):

The immune response, estimated by the GMT for RSV A and RSV B 50% serum 
neutralizing titers.

The immune response, estimated by the GMFR from baseline in RSV A and RSV B 50% 
serum neutralizing titers.

GMR, estimated by the ratio of the GMTs for RSV A and RSV B 50% serum 
neutralizing titers of the RSV vaccine group to the placebo group.

Geometric mean of the IgG levels against RSV prefusion F.

Geometric mean of the Ig levels to nonvaccine RSV antigens.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as MCAR is assumed.  For participants who discontinue from the study 
or have major protocol violations, all postdiscontinuation or postviolation observations will 
be censored.
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9.1.2.2. Safety
In maternal participants receiving 1 dose of investigational product:

The percentage of maternal participants reporting AEs through 1 month after vaccination.

The percentage of maternal participants reporting obstetric complications and SAEs 
through the end of the study.

The percentage of maternal participants reporting local reactions within 7 days of 
vaccination.

The percentage of maternal participants reporting systemic events within 7 days of 
vaccination.
Missing e-diary data will not be imputed; missing AE dates and missing AE intensity will be 
handled according to Pfizer safety rules.
9.2. Sample Size Determination
This is a case-driven study. Sample size is determined as the number of participants to be 
randomized that is expected to accrue the required number of primary endpoint cases in the 
evaluable population. In this study there are 2 primary endpoints, and success on either 
primary endpoint is sufficient (see Section 9.1); power for the study overall is therefore at 
least as high as the power for either primary endpoint individually. In order for the study to 
have at least 90% power to reject the null hypothesis for MA-LRTI due to RSV when true 
VE is 60%, a total of 124 cases of MA-LRTI due to RSV within 90 days of birth are required 
in the evaluable population. This also accounts for potential use of an alpha of 1.25% 
1-sided within the Hochberg multiplicity adjustment. There is no explicit case target for the 
endpoint of severe MA-LRTI due to RSV; depending on the assumed true VE, power for that 
individual hypothesis may be lower, but the power for the primary endpoint family will be at 
least 90%. Hypotheses about VE may be restated as hypotheses about the proportion of 
cases in the RSV vaccine group, conditional upon a fixed total number of cases. If this 
proportion is p, the null hypothesis H0: VE ≤20% is equivalent to H0: p ≥0.444; the 
assumption of VE = 60% corresponds to p = 0.286. Power was evaluated by the exact 
binomial test, and the case target established as that number k for which power is guaranteed 
to be at least 90%, for all k* ≥k. The calculation accounted for the study design 
(1:1 randomization of participants to RSV vaccine : placebo), a single planned interim 
analysis of efficacy (see Section 9.5), and an overall type 1 error of 2.5% 1-sided across the 
2 primary endpoints. 
This global study is planned to be conducted in the United States and other high-income 
countries as well as LMICs. Incidence rates of the primary endpoints are expected to vary in 
different regions. Based on a recently completed Phase 3 trial of an RSV vaccine, the 
assumed incidence rate for MA-LRTI due to RSV through 90 days in low-incidence 
countries, such as the United States, is approximately 1.75%; and in other regions,
approximately 3.90%. With these assumptions, and also allowing for 60% VE and 10% of 
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enrolled participants being nonevaluable, enrollment of approximately 6900 participants is 
planned for the study as a whole. The exact number of participants required to accrue the 
case target may be higher or lower than this, depending on incidence rates, observed VE, and 
the proportion of participants evaluable.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined for infant and maternal 
participants:
Population
Description
Enrolled 
All maternal participants who sign the ICD.
Randomly assigned to 
investigational product
All maternal participants who are assigned a randomization 
number in the IRT system.
Evaluable efficacy –
infant (per-protocol)
All infant participants who are eligible, are born to the 
maternal participants who received the investigational product 
to which they were randomized at least 14 days prior to 
delivery, have valid and determinate results for the proposed 
analysis, and have no major protocol violations. 
Modified intent-to-treat 
(mITT) efficacy – infant
All infant participants who are born to vaccinated maternal 
participants and have valid and determinate results for the 
proposed analysis.
Evaluable 
immunogenicity – infant
All infant participants who are eligible, are born to the 
maternal participants who received the investigational product 
to which they were randomized, have blood drawn for assay 
testing within the specified time frame, have valid and 
determinate assay results for the proposed analysis, and have 
no major protocol violations. 
Evaluable 
immunogenicity –
maternal
All maternal participants who are eligible, receive the 
investigational product to which they were randomized, have 
blood drawn for assay testing within the specified time frame, 
have valid and determinate assay results for the proposed 
analysis, and have no major protocol violations. 
mITT immunogenicity –
infant
All infant participants who are born to vaccinated maternal 
participants and have at least 1 valid and determinate assay 
result for the proposed analysis.
mITT immunogenicity –
maternal
All randomized maternal participants who receive 
investigational product and have at least 1 valid and 
determinate assay result for the proposed analysis. 
Safety – infant
All infant participants who are born to vaccinated maternal 
participants.
Safety – maternal
All randomized maternal participants who receive 
investigational product.  
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9.4. Statistical Analyses 
The SAP will be developed and finalized before database lock for the first planned analysis 
and will describe the participant populations to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data.  This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The analysis of efficacy will use a conditional exact test based on the 
binomial distribution of the number of disease cases in the RSV vaccine 
group, given the total number of cases in both groups. The incidence of 
MA-LRTI due to RSV and severe MA-LRTI due to RSV in infant 
participants will be evaluated in both groups up to 90 days, 120 days, 
150 days, and 180 days after birth.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population. 

The 2 primary endpoints of MA-LRTI due to RSV and severe 
MA-LRTI due to RSV will be tested in parallel using a Hochberg 
multiplicity adjustment procedure. Success of the trial requires 
rejection of the null hypothesis (ie, a CI lower bound >20%) for either 
one of the 2 primary endpoints.

The primary endpoint of severe MA-LRTI due to RSV may be demoted 
to a secondary endpoint, if there are insufficient cases for an adequately 
powered analysis. During the trial, blinded accrual of cases will be 
monitored and prior to any unblinding, a decision rule for this change 
will be established based on the total number of cases of severe 
MA-LRTI due to RSV. 

Testing of the 2 primary endpoints across the time intervals will follow 
a fixed sequence with a gatekeeping strategy. First, the hypothesis 
pertaining to the incidence of the 2 primary endpoints within 90 days 
after birth will be tested, at the full multiplicity-adjusted alpha level, 
using a Hochberg adjustment. If that null hypothesis cannot be rejected, 
testing ends. Otherwise, testing proceeds to the incidence within 120 
days after birth, at the full alpha level. Only primary endpoint(s) that
are successful at all earlier time intervals will be considered at 
subsequent intervals. Testing will proceed to the endpoints evaluated at 
150 days and 180 days, conditional on rejection of the null hypotheses 
for all earlier time intervals. 
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
There may be a single interim analysis of the MA-LRTI-due-to-RSV
endpoint when there is an adequate number of cases (at least half the 
target number within 90 days). Based on the fraction of cases included 
in the interim analysis, an alpha level will be derived based on a Lan-
DeMets implementation of the O’Brien-Fleming alpha spending 
function. For example, if there is a single interim analysis at exactly 
50% of the cases, the appropriate 1-sided significance levels are 0.0014 
at the interim analysis and 0.0245 at the final analysis. Implementation 
of these
1-sided significance levels ensures the overall type 1 error for the 
primary endpoint will be no more than 0.025. See Section 9.5 for more 
details.

At the interim analysis there will also be an assessment for futility, 
based on conditional power for the MA-LRTI-due-to-RSV endpoint. If 
the probability of success at the end of the trial is low, given the interim 
analysis results and the initially assumed VE is applied to the remaining 
data, consideration will be given to stopping the study for futility.

CIs for VE will be calculated using the appropriate multiplicity-adjusted 
alpha level α. If the lower 100(1 - α)% confidence limit for VE exceeds 
20%, the null hypothesis for that endpoint will be rejected.

At the end of the trial, the RSV vaccine may be deemed efficacious if 
there are 43 or fewer cases of MA-LRTI due to RSV in the RSV 
vaccine group out of the 124 total primary endpoint cases.  This 
corresponds to estimated VE = 47% with 95.1% CI = (22%, 64%). For 
severe MA-LRTI, assuming a total of 50 cases occur, the vaccine may 
be deemed efficacious if there are 14 or fewer cases in the RSV vaccine 
group.  This corresponds to estimated VE = 61% with 95.1% CI = 
(26%, 81%). For both of these examples, it is assumed a 1-sided alpha 
of 0.0245 applies to the endpoint in question. A smaller 
multiplicity-adjusted alpha may apply, leading to a higher VE required 
for success. 

Kaplan-Meier curves showing accrual of primary endpoint cases over 
180 days will be presented.
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Secondary

The analysis of secondary efficacy endpoints will use the exact 
conditional binomial method, as for the primary endpoint. Secondary 
endpoints will be examined at the final analysis only. VE will be 
estimated along with 2-sided 95% CI. 

Inference for the secondary endpoints will be conditional upon 
demonstrating success for the primary efficacy endpoint. The 
secondary endpoints of hospitalizations due to RSV and all-cause 
MA-LRTI will be tested in parallel so as to preserve the overall type 1 
error across primary and secondary endpoint families at no more than 
2.5% 1-sided. Multiplicity correction strategies will be defined in the 
SAP. VE for each secondary endpoint will be evaluated sequentially at 
90 days, 120 days, 150 days, and 180 days, as for the primary endpoint. 
Testing will only proceed to later time points conditional on success of 
all previous time points. 

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.
Exploratory

The incidence in infant participants of MA-RTIs due to RSV with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized.

The incidence in infant participants of MA-RTIs due to any cause with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized. All MA-RTIs and severe MA-LRTIs will be summarized 
separately.

The incidence in infant participants of MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The incidence in infant participants of severe MA-LRTIs due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The incidence in infant participants of hospitalization due to RSV 
occurring 181 to 730 days after birth will be summarized. 

The primary endpoint through 180 days after birth will be summarized 
separately as cases associated with RSV subgroup A or RSV subgroup 
B infection.

The primary endpoint through 180 days after birth will be summarized 
by interval from vaccination to delivery and by GA at the time of 
vaccination.
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
The incidence of MA-RTI due to any cause in maternal participants 
from vaccination through 180 days after delivery will be summarized. 
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting 
each event for each vaccine group.

A 3-tier approach will be used to summarize AEs. For both Tier 1 and 
Tier 2 events, the 95% CIs for the difference in the percentage of 
participants reporting the events between the RSV vaccine group and the 
placebo group will be calculated using the test statistic proposed by 
Miettinen and Nurminen; in addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in the percentage of 
participants reporting the events, based on the same test statistic and 
under the assumption that the test statistic is asymptotically normally 
distributed.  A Medical Dictionary for Regulatory Activities (MedDRA) 
preferred term is defined as a Tier 2 event if there are 1% or more 
participants in at least 1 vaccine group reporting the event.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Secondary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting 
each event for each vaccine group.

The safety analyses are based on the safety population. Participants will 
be summarized by the vaccine group corresponding to the vaccine they 
(for maternal participants) or their mothers (for infant participants) 
actually received. Missing e-diary data will not be imputed; missing AE 
dates and missing AE intensity will be addressed using the Pfizer safety 
rules.
Exploratory

These analyses will be described in the SAP, finalized before first 
database lock.
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9.4.3. Other Analyses 
9.4.3.1. Immunogenicity Analyses
Immunogenicity endpoints are exploratory in the study.  The analyses of immunogenicity 
endpoints will be based on the evaluable populations.  An additional analysis will be 
performed based on the mITT populations if there is enough difference between the mITT 
populations and the evaluable populations.  Immunogenicity data for maternal participants 
and infant participants will be summarized separately, with the exception of maternal-to-
infant placental transfer analysis.  Participants will be summarized according to the vaccine 
group to which they (for maternal participants) or their mothers (for infant participants) were 
randomized.
The secondary and exploratory immunogenicity endpoints will be described by the following 
summaries and the 95% CIs:

GMT of the RSV A and RSV B serum neutralizing titers at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMT of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, at each available time point by 
vaccine group (maternal participants and infant participants, separately).

GMFR for RSV A and RSV B serum neutralizing titers from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMFR of the combined RSV A/B serum neutralizing titer, defined as the geometric mean 
of the RSV A and RSV B serum neutralizing titers, from before vaccination to each 
available time point after vaccination by vaccine group (maternal participants only).

GMR of the RSV vaccine group to the placebo group for the RSV A and 
RSV B serum neutralizing titers at each available time point after vaccination (maternal 
participants and infant participants, separately).

GMR of the RSV vaccine group to the placebo group for the combined RSV A/B serum
neutralizing titers at each available time point after vaccination (maternal participants and 
infant participants, separately).

Geometric mean of the IgG levels against RSV prefusion F and Ig levels to nonvaccine 
RSV antigens at each available time point by vaccine group (maternal participants and 
infant participants, separately).

Geometric mean of IgG subclass levels (minimally IgG1) against RSV prefusion F at 
each available time point by vaccine group (maternal participants only).
Empirical reverse cumulative distribution curves (RCDCs) for combinations of time points 
and vaccine groups will be presented for RSV A and RSV B serum neutralizing titers.
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A sensitivity analysis will be performed to exclude immunogenicity data from mothers and 
their infants following onset of RSV infection between vaccination and delivery (based on 
evidence from the nonvaccine antigen assay). 
Subgroup analyses of the secondary and exploratory immunogenicity endpoints will be 
performed, including an analysis based on GA at the time of vaccination, time from 
vaccination to delivery, and by country subcategories. All subgroup analyses will be defined 
in the SAP.
In addition, the maternal-to-infant placental transfer ratio (infant/mother) of RSV A and 
RSV B serum neutralizing titers and associated 95% CI will be summarized.
9.4.3.2. Healthcare Utilization Analyses
Healthcare utilization endpoints are exploratory in the study; these analyses will be described 
in the SAP and finalized before first database lock. For these analyses, details of healthcare 
resource utilization for all infants will be assessed at each MA-RTI visit from birth through 
the last study visit (730 days after birth). Details of healthcare resource utilization will be 
summarized into a mean/median composite score, which may include the following: number 
and type (eg, respiratory, reactive airway disease [RAD]/asthma/wheezing) of medical visits 
(eg, outpatient, urgent care, emergency room, hospitalization, ICU), length of hospital stay, 
requirement for mechanical ventilation (yes/no, total number of episodes, total number of 
hours/days on treatment), requirement for IV fluids, requirement for respiratory diagnostic 
procedures (eg, chest radiograph, supplemental oxygen, pulse oximetry), requirement for 
prescriptions (eg, total number of prescriptions, selected respiratory medications [eg,
bronchodilators, corticosteroid therapy, racemic epinephrine]), and antibiotic use (eg, total 
number of prescriptions, number of use days).
9.5. Interim Analyses
An interim analysis may be performed to assess efficacy and safety after at least 50% of the 
planned number of cases of MA-LRTI due to RSV have occurred. Because of the relatively 
low number of cases of severe MA-LRTI due to RSV expected, the interim analysis will not 
consider that endpoint. Interim analysis results may be used for internal business decisions 
regarding future study planning, stopping for futility, or stopping for early success.  
The order of cases included in the interim analysis will be determined by the adjudication 
committee as those first confirmed as meeting the protocol-defined criteria. When the target 
number of cases for the interim analysis is reached, it is possible that additional potential 
cases will be under adjudication. These additional cases will be included in the interim 
analysis only if confirmed as cases by the EAC on the same day that the last per-protocol 
case is confirmed.
The analysis of efficacy will utilize an O’Brien-Fleming alpha spending rule based on the 
fraction of cases of MA-LRTI due to RSV available. For example, to control the overall 
type 1 error for the primary endpoint at 2.5% 1-sided, an interim analysis at 50% of the target 
number of cases would use a 1-sided significance level of 0.14%. The final analysis at the 
target number of cases would use a 1-sided significance level of 2.45%. The alpha levels 
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used at interim and final analyses will depend on the exact fraction of cases available at the 
interim analysis.
Testing of the primary endpoints at the interim analysis will follow the sequence of 
interval-specific tests as described in Section 9.4.1.  However, consideration will be given to 
stopping the study for efficacy only if all time intervals through 180 days indicate statistically 
significant efficacy. Secondary endpoints will not be tested at the interim analysis.
Futility will also be assessed using conditional power. Full details will be defined in the SAP. 
For example, if there are 62 cases available for the interim analysis, Table 7 indicates case 
splits for which stopping the study will be considered. The actual number of cases available 
may be slightly higher or lower than 62, and the decision rules amended accordingly.
Table 7.
Example of Estimated Vaccine Efficacy and Confidence Intervals at an 
Interim Analysis
Total Cases
RSV Vaccine 
Group Cases
Placebo Group 
Cases
VE (CI)a
Notes
62
29
33
12% (-49%, 49%)
Conditional power 
<20%b; possible 
futility declaration
62
15
47
68% (24%, 88%)
Maximum number 
of RSV cases 
permitted to 
declare VE >20%
Abbreviation: VE = vaccine efficacy.
a. 99.7% confidence level for efficacy declaration; 95% confidence level for futility.
b. Other conditional power levels may be considered as a trigger for a futility decision.
Before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan, and method of maintaining the study blind as per Pfizer’s standard 
operating procedures (SOPs) will be documented and approved in the DMC charter.  In 
addition, the analysis details must be documented and approved in an interim analysis SAP 
or final SAP.
9.5.1. Data Monitoring Committee 
This study will use an E-DMC.  Refer to the E-DMC charter for further details.
The E-DMC will review safety data at defined intervals as specified in the charter.  The 
E-DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.
The E-DMC may review unblinded data during closed meeting sessions; however, the 
sponsor will remain blinded and will not be permitted access to the randomization 
assignments until the database is locked and unblinded.
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After each meeting, the E-DMC will make recommendations that may include continuing the 
study with or without modification or pausing or stopping vaccination for safety or other 
reasons.
The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints, to regulatory authorities, as appropriate.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
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of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the maternal 
participant and answer all questions regarding the study.
Maternal participants must be informed that their participation is voluntary.  Maternal 
participants will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability 
and Accountability Act (HIPAA) requirements, where applicable, and the IRB/EC or study 
center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the maternal participant.
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Before any study-specific activity is performed, the investigator, or a person designated by 
the investigator, will obtain written informed consent from each maternal participant.  This 
will include written informed consent for the mother and the fetus during the pregnancy, and 
the infant’s continuation in the study after delivery.  Informed consent will be obtained from 
the father of the fetus/infant if mandated by local requirements.
Participants who are rescreened may be required to sign a new ICD as per IRB, local 
regulations, etc.
If during the study, the investigator determines that the maternal participant is for any reason 
no longer capable of providing informed consent, the infant’s continued participation in the 
study requires consent to be obtained from the parent(s)/legal guardian as determined by 
local regulations, legal requirements, and the IRB/EC. 
Note: For the infant participant, the term parent(s)/legal guardian denotes the “legally 
authorized representative.”
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its SOPs.
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In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (clinical study report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the US Basic 
Results document is posted to www.clinicaltrials.gov.
Documents Within Marketing Authorization Packages/Submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
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24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician.  Data will not 
be provided to applicants with significant conflicts of interest, including individuals
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan/contracts.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
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the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the site Source Data Agreement 
Plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;
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
Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study (or 
study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
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question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
For maternal immunization clinical studies conducted in pregnant women, data on the EDP
including any SAEs/nonserious AEs as well as pregnancy outcomes are collected and 
analyzed in the clinical database. All SAEs are reported to Pfizer Safety using the Vaccine 
SAE Reporting Form. In case of a new pregnancy in a maternal participant before the end of 
the study, any exposure to the investigational product is reportable to Pfizer Safety within 
24 hours of investigator awareness using the Vaccine SAE Reporting Form/EDP 
supplemental form.
The term “participant” in this section refers to (1) the maternal participant and her fetus; and 
after delivery (2) the maternal participant and (3) the infant participant.
10.2.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming
intent.  Such overdoses should be reported regardless of sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (eg, cesarean section, endoscopy, appendectomy): the 
condition that leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs)
An NDCMC is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
10.2.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
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serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording safety events on the CRF and 
for reporting safety events on the Vaccine SAE Reporting Form to Pfizer Safety.  These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and (3) 
occupational exposure. 
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
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terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study via 
occupational exposure
None
Occupational exposure 
(regardless of whether 
associated with an AE)  

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Reporting
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE.
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Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING
to describe the maximum intensity of the AE. For purposes of 
consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent 
intervention indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.
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
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused the 
event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible.  This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any anonymized 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
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10.2.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data become 
available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see next 
section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
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10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
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
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.4. Appendix 4: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The definitions and procedures detailed in this appendix are in accordance with International 
Organization for Standardization (ISO) 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.4.1. Definition of AE and Adverse Device Effect (ADE)
AE and ADE Definition 

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational medical device.  
This definition includes events related to the investigational medical device or 
comparator and events related to the procedures involved except for events in users or 
other persons, which only include events related to investigational devices.

An ADE is defined as an AE related to the use of an investigational medical device.  
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
10.4.2. Definition of Serious Adverse Event, Serious Adverse Device Effect, and 
Unanticipated Serious Adverse Device Effect
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is an AE that:
a. Led to death. 
b. Led to serious deterioration in the health of the participant, that either resulted in:

A life-threatening illness or injury.  The term “life-threatening” in the definition of 
serious refers to an event in which the participant was at risk of death at the time of 
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the event. It does not refer to an event that hypothetically might have caused death, 
if it were more severe.

A permanent impairment of a body structure or a body function.

Inpatient or prolonged hospitalization.  Planned hospitalization for a preexisting 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE.

Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
Serious Adverse Device Effect (SADE) Definition

A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE.
Unanticipated Serious Adverse Device Effect (USADE) Definition

A USADE is a serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis management 
file.
10.4.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance.  Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
10.4.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE, and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator 
to review all documentation (eg, hospital progress notes, laboratory reports, and 
diagnostic reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information in 
the participant’s medical records, in accordance with the investigator’s normal clinical 
practice and on the appropriate form of the CRF.
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
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of following the reporting process described in the IP 
manual.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency.  This includes any amendment to the device design to prevent 
recurrence.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE/device deficiency 
reported during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
“severe” should not be confused with an SAE. “Severe” is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as “severe.”

An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as “severe.”
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency.
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
A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency and has 
provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor.  However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE/SAE/Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE/SAE/ device deficiency 
as fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
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10.4.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred 
method to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.
10.4.6. Reporting of SADEs
SADE Reporting to Pfizer Safety 
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.
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10.5. Appendix 5: Background Factors
1. Information on the following will be collected at Visit 1, Visit 4 (12-Month), and 
Visit 6 (24-Month) for all infant participants:

Educational level of parent(s) or legal guardian(s).

Exposure to smoke (including tobacco smoke).

Number of persons in the household ≥18 years of age.

Number of children <18 years of age in the household and if they attend school/ 
daycare.
o
Number of children in the household under 5 years of age (under 60 months).
o
Number of children in the household 5 years of age (60 months).
2. Information on the following will be collected at each postbirth visit:

Childcare/daycare (for infant participants).

Breastfeeding information (including whether or not breastfeeding is exclusive).
3. Information on the following will be collected at each RTI study visit:

Number of missed days of work for parent(s) or legal guardian(s) due to the infant 
participant’s illness.
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10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria Checklist 
for MA-RTI Visit – Infant Participants
When an infant RTI medical visit criterion is met or confirmed, the site will obtain records 
from the medical visit and capture the healthcare information as detailed below in the eCRF. 
This information is based on respiratory-related assessments including examination findings, 
clinical findings, and any pathogen-related assessments/findings. 
Medical Visit - Visit Details and Assessment Requirements
Note: This should not be linked to a study visit but may overlap with the RTI study visit. 
The following fields and clinical assessment details should be obtained from relevant 
records for the medically attended event prior to each RTI study visit to support the 
assessment of the RTI event.

Reason for visit including date/time, eg,
o
Nasal discharge for 24 hours or more.
o
Difficulty breathing, labored breathing, or rapid breathing for any duration.
o
Cough.
o
Inability to feed for any duration due to respiratory symptoms.
o
Apnea.
o
Any other respiratory symptom of concern.

Location of medical visit (inpatient clinic, outpatient clinic, emergency department, 
urgent care, hospitalization, home visit, other). Note: study visits should NOT be 
recorded here.
o
If hospital visit, was this triggered by an RTI (include details pertaining to duration
as well as admission and discharge information and records)?

Clinical findings pertaining to respiratory symptoms and/or RTI, as detailed below but 
not limited to:
o
Presence or absence of pertinent examination findings, eg, apnea (documented as per 
chart), wheezing, fever, cough, nasal congestion, intercostal retractions, lower chest 
wall indrawing, grunting, crackles, decreased breath sounds, other abnormal breath
sounds, dry mucous membranes, skin tenting, sunken fontanelle, difficulty feeding,  
wheezing, failure to respond/unconsciousness, etc. 
o
Respiratory rate from highest/worst value of visit.
o
Oxygen saturation (SpO2) from lowest/worst value of visit.
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o
Oxygen supplementation (assisted ventilation, including type of respiratory assistance 
[respirator, “state-of-the-art” occlusive nasal prongs, face tent, etc]).

Days of supplementary oxygen.

Use of nasal cannula.

Use of high-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive).
o
Heart rate from worst value of visit when performed consistently.
o
Additional clinical or respiratory related assessments including chest x-ray 

Local test results for RSV as part of routine clinical care:
o
Testing platform used (clinical list of all platforms and validated by research).
o
Result (list: positive, negative, indeterminate, other).

Record the provider diagnosis, including any causative pathogen (if applicable), eg, RSV 
bronchiolitis, asthma, influenza, etc.

Obtain details of all prescribed medications including IV fluid usage.

Obtain details of all AEs/SAEs in line with study requirements. Note: MA-RTIs are not 
AEs/SAEs.
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10.7. Appendix 7: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ADE
adverse device effect
AESI
adverse event of special interest
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
Apgar
appearance, pulse, grimace, activity, and respiration
AST
aspartate aminotransferase
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
Clinical Laboratory Improvement Amendments
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EAC
endpoint adjudication committee
EACC
endpoint adjudication committee charter
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine 
GA
gestational age
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Abbreviation
Term
GBS
group B streptococcal
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBIG
hepatitis B immune globulin
HBV
hepatitis B virus
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IAP
intrapartum antibiotic prophylaxis
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
Ig
immunoglobulin
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IRT
interactive response technology
ISF
investigator site file
ISO
International Organization for Standardization
IUI
intrauterine insemination
IV
intravenous
IWR
interactive Web-based response
LFT
liver function test
LMIC
lower- and middle-income country
LMP
last menstrual period
LRTI
lower respiratory tract illness
MA-LRTI
medically attended lower respiratory tract illness
MA-RTI
medically attended respiratory tract illness
MCAR
missing completely at random
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NAAT
nucleic acid amplification technology
NDCMC
newly diagnosed chronic medical condition
PCD
primary completion date
PCR
polymerase chain reaction
PFS
prefilled syringe
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Abbreviation
Term
PT
prothrombin time
RAD
reactive airway disease
RCDC
reverse cumulative distribution curve
RSV
respiratory syncytial virus
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RTI
respiratory tract illness
RT-PCR
reverse transcription–polymerase chain reaction
SAE
serious adverse event
SADE
serious adverse device effect
SAP
statistical analysis plan
SMS
short message service
SoA
schedule of activities
SOP
standard operating procedure 
SpO2
oxygen saturation
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Tdap
tetanus, diphtheria, and acellular pertussis vaccine
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
VE
vaccine efficacy
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11. REFERENCES
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Shi T, McAllister DA, O’Brien KL, et al. Global, regional, and national disease burden 
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Scheltema NM, Gentile A, Lucion F, et al. Global respiratory syncytial virus-associated 
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Parikh RC, McLaurin KK, Margulis AV, et al. Chronologic age at hospitalization for 
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Blanken MO, Rovers MM, Molenaar JM, et al. Respiratory syncytial virus and recurrent 
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Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk 
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Weber MW, Mulholland EK, Greenwood BM. Respiratory syncytial virus infection in 
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Glezen WP, Taber LH, Frank AL, et al. Risk of primary infection and reinfection with 
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American Academy of Pediatrics. Respiratory syncytial virus. In: Kimberlin DW, Brady 
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Prescott WA Jr, Doloresco F, Brown J, et al. Cost effectiveness of respiratory syncytial 
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13
Synagis [prescribing information]. Gaithersburg, MD: MedImmune LLC; 2017.
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14
Munoz FM, Ralston SL, Meissner HC. RSV recommendations unchanged after review 
of new data. AAP News 19 Oct 2017. Available from: 
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The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus 
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Baker CJ, Carey VJ, Rench MA, et al. Maternal antibody at delivery protects neonates 
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Dangor Z, Kwatra G, Izu A, et al. Correlates of protection of serotype-specific capsular 
antibody and invasive group B Streptococcus disease in South African infants. Vaccine
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Skoff TH, Blain AE, Watt J, et al. Impact of the US maternal tetanus, diphtheria, and 
acellular pertussis vaccination program on preventing pertussis in infants <2 months of 
age: A case-control evaluation. Clin Infect Dis 2017;65(12):1977-83.
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Baxter R, Bartlett J, Fireman B, et al. Effectiveness of vaccination during pregnancy to 
prevent infant pertussis. Pediatrics 2017;139(5):e20164091.
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Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and 
protection of their infants. N Engl J Med 2014;371(10):918-31. 
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Benowitz I, Esposito DB, Gracey KD, et al. Influenza vaccine given to pregnant women 
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22
Forbes ML, Kumar VR, Yogev R, et al. Serum palivizumab level is associated with 
decreased severity of respiratory syncytial virus disease in high-risk infants. Hum 
Vaccin Immunother 2014;10(10):2789-94.
23
Schmoele-Thoma B, Falsey AR, Walsh EE, et al. Phase 1/2, first-in-human study of the 
safety, tolerability, and immunogenicity of an RSV prefusion F-based subunit vaccine 
candidate [poster 2755]. Poster presented at IDWeek; 02-06 Oct 2019; Washington, DC.
24
McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer 
bound to a prefusion-specific neutralizing antibody. Science 2013;340(6136):1113-7.
25
Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants 
despite prior administration of antigenic inactivated vaccine. Am J Epidemiol
1969;89(4):422-34. 
26
Graham BS. Biological challenges and technological opportunities for respiratory 
syncytial virus vaccine development. Immunol Rev 2011;239(1):149-66.
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Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial 
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28    Novavax. Phase 3 and beyond: the RSV F nanoparticle vaccine for infants via maternal 
immunization [slide 26]. Presentation at the World Vaccine Congress; 14-17 Apr 2019; 
Washington, DC. Available from: https://novavax.com/download/files/posters/2019-
World_Vaccine_Congress/2019.04.16-World_Vaccine_Congress.pdf. Accessed: 25 Nov 
2019.
29     Regen AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization 
during pregnancy in 4 high-income countries, 2010–2016.  Clin Infect Dis 
2018;67(12):1915-8. Available from: https://doi.org/10.1093/cid/ciy439. Accessed: 
25 Nov 2019.
30     Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: case definition & guidelines for 
data collection, analysis, and presentation of immunisation safety data. Vaccine. 
2016;34(49):6047-56.
31
European Commission. Ethical considerations for clinical trials on medicinal products 
conducted with minors. 18 Sep 2017. Available from:  
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/2017_09_18_ethical_consid_ct_with_minors.pdf. Accessed 21 Feb 2019.
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PPD
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PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671008
Final Protocol, 05 December 2019
PFIZER CONFIDENTIAL
CT02-GSOP-RF18 2.0 Maternal Immunization Protocol Template (Phase 1 2 3 4) (01 October 2018)
Page 1
A PHASE 3, RANDOMIZED, DOUBLE- OR OBSERVER-BLINDED, 
PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND 
SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F 
SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING 
PREGNANCY
Investigational Product Number:
PF-06928316 
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine 
United States (US) Investigational New 
Drug (IND) Number:
017931
European Clinical Trials Database 
(EudraCT) Number:
2019-002943-85
Protocol Number:
C3671008
Phase:
3
Short Title: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants 
Born to Women Vaccinated During Pregnancy.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Original protocol
05 December 2019
Not applicable (N/A)
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
1. PROTOCOL SUMMARY...................................................................................................10
1.1. Synopsis ..................................................................................................................10
1.2. Schematic for Study Participants ............................................................................17
1.2.1. Study Design – Maternal Participants ........................................................17
1.2.2. Study Design – Infant Participants .............................................................18
1.2.3. Schedule of Activities for Maternal Participants........................................19
1.2.3.1. Schedule of Activities for Maternal Participants: RTI 
Surveillance for Medically Attended Respiratory Tract Illness 
Visits (Vaccination Until the End-of-Study Visit) ............................21
1.2.4. Schedule of Activities for Infant Participants.............................................22
1.2.4.1. Schedule of Activities for Infant Participants: Medically 
Attended Respiratory Tract Illness Assessment Visits During 
the Study............................................................................................24
2. INTRODUCTION ...............................................................................................................26
2.1. Study Rationale .......................................................................................................26
2.2. Background .............................................................................................................27
2.3. Benefit/Risk Assessment.........................................................................................28
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................29
3.1. Infant Participants ...................................................................................................29
3.2. Maternal Participants...............................................................................................33
3.3. Protocol-Defined Efficacy Endpoints .....................................................................34
4. STUDY DESIGN.................................................................................................................35
4.1. Overall Design.........................................................................................................35
4.1.1. Approximate Duration of Participation for Each Participant .....................36
4.1.2. Approximate Number of Participants.........................................................36
4.2. Scientific Rationale for Study Design.....................................................................37
4.3. Justification for Dose ..............................................................................................37
4.4. End of Study Definition ..........................................................................................38
5. STUDY POPULATION......................................................................................................38
5.1. Inclusion Criteria.....................................................................................................38
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5.1.1. Inclusion Criteria – Maternal Participants..................................................38
5.1.2. Inclusion Criteria – Infant Participants.......................................................40
5.2. Exclusion Criteria....................................................................................................41
5.2.1. Exclusion Criteria – Maternal Participants.................................................41
5.2.2. Exclusion Criteria – Infant Participants......................................................43
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants ................43
5.3. Lifestyle Considerations..........................................................................................43
5.4. Screen Failures ........................................................................................................43
6. STUDY INTERVENTION..................................................................................................44
6.1. Study Intervention(s) Administered........................................................................44
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........44
6.1.2. Placebo........................................................................................................45
6.1.3. Administration............................................................................................45
6.1.4. Medical Devices .........................................................................................46
6.2. Preparation/Handling/Storage/Accountability ........................................................46
6.2.1. Preparation and Dispensing........................................................................47
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................47
6.3.1. Blinding of Study Site Personnel................................................................47
6.3.2. Blinding of the Sponsor..............................................................................48
6.3.3. Allocation to Investigational Product .........................................................48
6.3.4. Breaking the Blind......................................................................................49
6.4. Study Intervention Compliance...............................................................................49
6.5. Concomitant Therapy..............................................................................................49
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................49
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal 
Participants.......................................................................................................49
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................50
6.5.4. Permitted Concomitant Vaccinations and Treatments – Infant 
Participants.......................................................................................................50
6.5.5. Recording Nonstudy Vaccinations and Concomitant Medications –
Infant Participants............................................................................................51
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6.6. Dose Modification...................................................................................................51
6.7. Intervention After the End of the Study..................................................................51
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................51
7.1. Discontinuation of Study Intervention ....................................................................51
7.2. Participant Discontinuation/Withdrawal From the Study.......................................51
7.3. Withdrawal of Consent............................................................................................52
7.4. Lost to Follow-up....................................................................................................52
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................53
8.1. Efficacy Assessments..............................................................................................54
8.1.1. Efficacy Assessments – Infant Participants................................................54
8.1.1.1. Midturbinate Nasal Swab Collection and Testing 
Requirements for Endpoint Confirmation – Infant Participants........54
8.1.1.2. Events for Adjudication and Submission Guidance –
Infant Participants..............................................................................55
8.1.2. Exploratory Efficacy Assessments – Maternal Participants.......................56
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal 
and Infant Participants .....................................................................................56
8.1.4. Immunogenicity Assessments ....................................................................56
8.1.4.1. Total Volume of Blood Collected – Maternal Participants.......56
8.1.4.2. Total Volume of Blood Collected – Infant Participants............56
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant 
Participants ........................................................................................57
8.1.4.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development – Maternal and Infant 
Participants ........................................................................................57
8.1.4.5. Respiratory Pathogens – Infant Participants .............................58
8.1.4.6. Biological Samples – Maternal and Infant Participants............58
8.2. Safety Assessments .................................................................................................58
8.2.1. Participant Electronic Diary – Maternal Participants .................................59
8.2.1.1. Local Reactions – Maternal Participants...................................60
8.2.1.2. Systemic Events – Maternal Participants..................................61
8.2.1.3. Temperature – Maternal Participants ........................................63
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8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant 
Participants.......................................................................................................63
8.3. Adverse Events and Serious Adverse Events..........................................................63
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......64
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................65
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................66
8.3.2. Method of Detecting AEs and SAEs ..........................................................66
8.3.3. Follow-up of AEs and SAEs.......................................................................66
8.3.4. Regulatory Reporting Requirements for SAEs...........................................67
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Investigational Product ..........................................................................67
8.3.5.1. Exposure During Breastfeeding ................................................67
8.3.5.2. Occupational Exposure .............................................................67
8.3.6. Medical Device Incidents (Including Malfunctions)..................................68
8.3.6.1. Time Period for Detecting Medical Device Incidents...............69
8.3.6.2. Follow-up of Medical Device Incidents....................................69
8.3.6.3. Prompt Reporting of Medical Device Incidents to Sponsor .....69
8.3.6.4. Regulatory Reporting Requirements for Medical Device 
Incidents ............................................................................................69
8.3.7. Medication Errors .......................................................................................70
8.4. Treatment of Overdose............................................................................................71
8.5. Pharmacokinetics ....................................................................................................71
8.6. Pharmacodynamics..................................................................................................71
8.7. Genetics...................................................................................................................71
8.7.1. Specified Genetics ......................................................................................71
8.8. Biomarkers ..............................................................................................................71
8.9. Health Economics ...................................................................................................71
8.10. Procedures – Maternal Participants.......................................................................71
8.10.1. Screening and Vaccination Visit (Clinic; Day -28 to Day 1 – Visit 
1) ......................................................................................................................71
8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After 
Vaccination).....................................................................................................76
8.10.3. Delivery (Maternity Unit).........................................................................76
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8.10.4. 6-Month-Postdelivery Visit (Clinic or Telephone; 180 to 210 Days 
After Delivery).................................................................................................78
8.10.5. Unscheduled Reactogenicity Visits..........................................................78
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria –
Maternal Participants .......................................................................................80
8.11. Procedures – Infant Participants............................................................................81
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After 
Birth)................................................................................................................81
8.11.2. Visit 2 – 1-Month Follow-up (Clinic, 28 to 48 Days After Birth) ...........82
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic, 180 to 210 Days After 
Birth)................................................................................................................83
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 
Days After Birth) .............................................................................................84
8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days 
After Birth; Infant Participants Born During the First Year of the Study 
Only) ................................................................................................................86
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 
742 Days After Birth; Infant Participants Born During the First Year of 
the Study).........................................................................................................86
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 
Months After Delivery)....................................................................................87
8.11.7.1. RTI Associated With a Medical Visit – Hospital, Home, 
or Clinic Visit ....................................................................................87
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit 
Criteria .............................................................................................................89
8.12. Communication and Use of Technology...............................................................90
9. STATISTICAL CONSIDERATIONS ................................................................................91
9.1. Estimands and Statistical Hypotheses.....................................................................91
9.1.1. Estimands – Infant Participants ..................................................................91
9.1.1.1. Efficacy .....................................................................................91
9.1.1.2. Immunogenicity ........................................................................92
9.1.1.3. Safety.........................................................................................92
9.1.2. Estimands – Maternal Participants .............................................................92
9.1.2.1. Immunogenicity ........................................................................92
9.1.2.2. Safety.........................................................................................93
9.2. Sample Size Determination.....................................................................................93
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9.3. Populations for Analysis .........................................................................................94
9.4. Statistical Analyses .................................................................................................95
9.4.1. Efficacy Analyses .......................................................................................95
9.4.2. Safety Analyses ..........................................................................................98
9.4.3. Other Analyses............................................................................................99
9.4.3.1. Immunogenicity Analyses.........................................................99
9.4.3.2. Healthcare Utilization Analyses..............................................100
9.5. Interim Analyses ...................................................................................................100
9.5.1. Data Monitoring Committee.....................................................................101
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................103
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............103
10.1.1. Regulatory and Ethical Considerations ..................................................103
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................103
10.1.2. Financial Disclosure ...............................................................................104
10.1.3. Informed Consent Process ......................................................................104
10.1.4. Data Protection .......................................................................................105
10.1.5. Dissemination of Clinical Study Data ....................................................105
10.1.6. Data Quality Assurance ..........................................................................107
10.1.7. Source Documents..................................................................................108
10.1.8. Study and Site Closure............................................................................108
10.1.9. Publication Policy...................................................................................109
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................109
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................111
10.2.1. Definition of AE .....................................................................................111
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs).................112
10.2.3. Definition of SAE...................................................................................112
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs.....................113
10.2.5. Reporting of SAEs..................................................................................116
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......118
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10.4. Appendix 4: Medical Device Incidents: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting..................................................120
10.5. Appendix 5: Background Factors........................................................................122
10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria 
Checklist for MA-RTI Visit – Infant Participants...................................................123
10.7. Appendix 7: Abbreviations .................................................................................125
11. REFERENCES ................................................................................................................128
LIST OF TABLES
Table 1.
Endpoint Events and Definitions in Infant Participants ...........................29
Table 2.
Endpoint Events and Definitions in Maternal Participants.......................33
Table 3.
Composition of the RSV Vaccine Intended for Clinical Evaluation 
After Reconstitution With Diluent............................................................44
Table 4.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained....................................................................................................57
Table 5.
Grading Scale for Local Reactions...........................................................61
Table 6.
Grading Scale for Systemic Events ..........................................................62
Table 7.
Ranges for Fever.......................................................................................63
Table 8.
Example of Estimated Vaccine Efficacy and Confidence Intervals 
at an Interim Analysis.............................................................................101
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Indication
Pfizer’s respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSVpreF) 
is a prophylactic vaccine that is being investigated for the prevention of medically attended
RSV-associated lower respiratory tract illness (LRTI) in infants by active immunization of 
pregnant women.
Rationale
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given the global burden of disease, maternal immunization offers an attractive 
strategy for infant disease prevention.  Both preclinical studies in animals and interim data 
from a Phase 1/2 study in healthy nonpregnant adults have demonstrated acceptable 
tolerability and safety of RSVpreF.  A robust immune response has also been observed in 
participants from the aforementioned trial. RSVpreF is currently under assessment in healthy 
pregnant women 18 through 49 years of age (Study C3671003: A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blinded Trial to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT 04032093).
This randomized, double- or observer-blinded, placebo-controlled Phase 3 study is designed 
to evaluate the efficacy and safety of maternal immunization with RSVpreF against 
medically attended lower respiratory tract illness (MA-LRTI) in infants.  
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Objectives, Estimands, and Endpoints 
Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
Vaccine efficacy (VE), 
defined as the relative risk 
reduction of the endpoint in 
the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the endpoint adjudication committee
(EAC): 

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:   

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants born 
to maternal participants 
receiving 1 dose of 
investigational product, 
the percentage of 
participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

Adverse events (AEs) from birth to 
1 month of age.

Serious adverse events (SAEs) and 
newly diagnosed chronic medical 
conditions (NDCMCs):
o
from birth through 6 months of 
age (first RSV season for all 
infant participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born 
to maternal participants enrolled 
during the first year of the study).
Secondary Efficacy Objectives
–
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria.

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause MA-LRTI.
VE, defined as the relative 
risk reduction of the endpoint 
in the RSV vaccine group 
compared to the placebo 
group, for infant participants 
born to maternal participants 
receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with protocol-
defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, 
if the analysis at 90 days meets 
efficacy criteria. 

occurring within 150 days after birth, 
if the analysis at 120 days meets 
efficacy criteria.

occurring within 180 days after birth, 
if the analysis at 150 days meets 
efficacy criteria.
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Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of medically attended 
respiratory tract illness 
(MA-RTI) due to RSV.
RSV-positive MA-RTI as confirmed by 
the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due 
to RSV.
Hospitalization due to RSV occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants older than
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause MA-LRTI.
MA-LRTIs due to any cause occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–
specific MA-LRTI as confirmed by the 
EAC occurring within 181 days after birth.
To describe the non-RSV 
infectious etiology of MA-RTI 
in the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned MA-RTI 
visits occurring within 181 days after 
birth.
To evaluate RSV-neutralizing 
antibody titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A– and RSV B–neutralizing 
antibody titers measured at birth. 
To assess the impact of RSVpreF 
on RSV illness based on 
socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors (eg, 
breastfeeding, maternal smoking, number 
of household members).
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To assess the effect of RSVpreF 
on healthcare utilization. 
Mean/median composite score 
summarizing healthcare utilization, which 
may include the following: number and 
type of medical visits, length of hospital 
stay, requirement for mechanical 
ventilation, requirement for respiratory 
diagnostic procedures, requirement for 
intravenous (IV) fluids, requirement for 
prescriptions, and antibiotic use.
Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimand
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery 
study visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by RSVpreF.

RSV A– and RSV B–neutralizing 
antibody titers and preF 
immunoglobulin G (IgG) titers 
measured:

before vaccination.

at delivery.
Overall Design
This is a Phase 3, multicenter, randomized, double- or observed-blinded, placebo-controlled 
study to assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons.
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This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis section (Section 9.2).  There is no specific case target for 
the additional primary endpoint of severe MA-LRTI. The total enrollment number of 
maternal participants may vary depending on the incidence rate of the primary endpoint in 
the infant participants, the true underlying VE, and a potential early stop for efficacy or 
futility. In the event that efficacy in the infant population is demonstrated at the interim 
analysis, enrollment of maternal participants may continue in order to obtain safety 
evaluations in an adequate number of maternal and infant participants to support vaccine 
registration with national health authorities. 
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It is anticipated that approximately 6900 
mother-infant pairs may be needed to accumulate 124 per-protocol cases.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive RSVpreF or 
placebo.  For the RSV vaccine group, a single dose and formulation of RSVpreF will be 
selected based on data from the maternal C3671003 study (ClinicalTrials.gov identifier: NCT 
04032093).  The selected dose of RSV prefusion F antigen in RSVpreF will be 120 µg 
(60 µg A and 60 µg B) or 240 µg (120 µg A and 120 µg B).  The selected formulation will be 
with or without aluminum hydroxide (Al[OH]3).
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.  
Infants born to women who receive RSVpreF or placebo in their second or third trimester 
will be referred to as “infant participants.” Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their proposed 12 months of participation.  For all infant participants, data will be 
collected for any medically attended respiratory illness to assess for cases of LRTI due to 
RSV (efficacy endpoint). Additionally, throughout the study, all respiratory illnesses, SAEs, 
and NDCMCs reported will be assessed in this population. For infant participants enrolled 
during the first year of the study, the extended 12-month study duration will involve longer-
term respiratory tract illness (RTI) surveillance and safety oversight to address safety and the 
possibility of conferred enhanced protection (antibody persistence) during a second RSV 
season.
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. 
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Planned Duration
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on gestational age (GA) at the time of vaccination and 
when the infant is actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth.
Data Monitoring Committee
This study will use an external data monitoring committee (E-DMC) to monitor vaccine 
safety and efficacy and study futility.  
Statistical Methods
The primary hypothesis to be tested is that VE with respect to MA-LRTI due to RSV or 
severe MA-LRTI due to RSV in infants within at least 90 days after birth is more than 20%, 
relative to placebo. The 2 primary endpoints will be tested in parallel using a Hochberg 
multiplicity adjustment procedure. VE will be estimated using the exact conditional binomial 
method. There will also be hierarchical testing of the primary endpoints to 120 days, 
150 days, and 180 days, conditional on success of the analysis for the shorter intervals. A 
single interim analysis of the primary endpoint with the opportunity to stop the study for 
efficacy or futility may be included. At the end of the trial, the RSV vaccine may be deemed 
efficacious if there are 43 or fewer cases of MA-LRTI due to RSV in the RSV vaccine group 
out of the 124 total primary-endpoint cases.  This corresponds to estimated VE = 47% with 
95.1% confidence interval (CI) = (22%, 64%). For severe MA-LRTI, assuming a total of 
50 cases occur, the vaccine may be deemed efficacious if there are 14 or fewer cases in the 
RSV vaccine group.  This corresponds to estimated VE = 61% with 95.1% CI = (26%, 81%).
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1.2. Schematic for Study Participants
1.2.1. Study Design – Maternal Participants
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1.2.2. Study Design – Infant Participants
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Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
1.2.3. Schedule of Activities for Maternal Participants
Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic or Telephone
Informed consent for maternal participant and her infant
X
Assign single maternal participant identifier 
X
Demography
X
Medical history including obstetric historyd
X
Record current alcohol, tobacco, marijuana, or any illicit drug usage
X
Targeted physical examination including vital signs 
X
Record details of any antenatal and/or postnatal steroid treatment, 
monoclonal antibodies, blood products, or Rho(D) immune globulin
X
X
X
X
Record details of intrapartum antibiotic prophylaxis (IAP) for maternal 
group B streptococcal colonization
X
Record nonstudy vaccine information
X
X
X
X
Review eligibility criteria
X
X
X
Review temporary delay criteria
X
Blood draw for serologic assessment (~15 mL) 
X
X
Assign randomization and container number
X
E-diary training, dispense digital thermometer and measuring devicee
X
Obtain and record baseline assessment of prespecified systemic events 
prior to vaccination in the e-diary
Administer investigational product
X
Postvaccination observation (at least 30 minutes) and assessment of 
immediate adverse events
X
Record pregnancy outcome information
X
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Visit Description
Screening and 
Vaccinationa
1-Month Follow-upb
Deliveryc
6-Month Postdelivery
Visit Window (Days)
Day -28 to Day 1
28 to 42 Days
After Vaccination
180 to 210 Days
After Delivery
Type of Visit
Clinic
Clinic or Telephone
Maternity Unit
Clinic or Telephone
Review e-diary dataf
X--------------------------
Record adverse events, as appropriateg
X--------------------------
Record serious adverse events, as appropriateg
X
X
X
X
Record details pertaining to MA-RTI visith
Assessment of confirmed MA-RTI events during the study as detailed in Section 1.2.3.1 of the 
schedule of activities
Abbreviations: e-diary = electronic diary; IAP = intrapartum antibiotic prophylaxis; MA-RTI = medically attended respiratory tract illness.
a.
In countries/locales where certain prenatal assessments are not routinely performed, prerandomization assessments and test results to confirm maternal 
participant eligibility for this clinical trial can be obtained and reviewed by the investigator or qualified designee up to 28 days prior to vaccination. 
b.
The 1-month follow-up visit will not be performed if delivery occurs before this visit. Active elicitation and collection of AEs and SAEs through 28 days 
after vaccination must occur even if delivery occurs within 28 days after vaccination. Once delivery occurs, the visit windows are calculated based on the 
delivery date.
c.
The delivery visit includes the time from when a participant is admitted into labor through discharge following delivery of her infant. Please see
Section 8.10.3 for required protocol assessments at this visit.
d.    Where an obstetric ultrasound examination is not performed at ≥18 weeks of pregnancy as part of prenatal standard of care, perform an ultrasound 
examination. As part of the obstetric history, details regarding the last menstrual period (LMP) and estimated delivery date (EDD) are to be recorded.
e.    Maternal participants will be issued a measuring device to measure local reactions and a digital thermometer for recording daily temperatures, and will be 
provided with instructions on their use. Maternal participants and or the field worker (as per local practice) will record (in an e-diary) a baseline assessment 
of prespecified systemic events prior to vaccination and reactogenicity events from Day 1 to Day 7 following vaccination (where Day 1 is the day of 
vaccination).  Remind maternal participants that the study staff/field worker may contact them to obtain additional information on events entered into the e-
diary.  Ask maternal participants to contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to Day 7 following 
vaccination, to determine if an unscheduled reactogenicity visit is required. Based on local rules of practice, the maternal participant may be referred to the 
appropriate healthcare facility at the discretion of a field worker if there are any concerns.
f.    Site staff will review e-diary data online at frequent intervals for the 7 days following vaccination to evaluate maternal participant compliance and as part of 
the ongoing safety review.
g.    The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected. Please see Section 8.3.1 for reporting requirements 
and timelines.
h.    A confirmed MA-RTI is defined as an expected RTI event based on the assessments detailed in the schedule of assessments in Section 1.2.3.1. These events 
will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product.
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1.2.3.1. Schedule of Activities for Maternal Participants: RTI Surveillance for Medically Attended Respiratory Tract Illness
Visits (Vaccination Until the End-of-Study Visit)
Visit Description
Assessments of  MA-RTIa
Visit Window
As Soon as Possible After Confirmed MA-RTI 
Type of Visit
Telephone
Record details of a confirmed MA-RTI 
X
Details of an acute illness visit AND a report of 1 or more of the following RTI
signs and symptoms: 

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
X
Obtain standard-of-care records, including local NAAT testing results (if 
applicable)b
X
Record nonstudy vaccine information
X
Record AEs and SAEs, as appropriatec
X
Complete the CRF with details 
X
Abbreviations: CRF = case report form; MA-RTI = medically attended respiratory tract illness; NAAT = nucleic acid amplification technology; RSV = 
respiratory syncytial virus; RTI = respiratory tract illness.
a.
Confirmed cases of MA-RTI will be collected from vaccination until the maternal participant completes the study. The assessment of the event would 
involve a telephone call, or a clinic visit if determined by the investigator to be warranted. 
b.
Site staff will review and collect data pertaining to the illness, including location of infection (upper or lower RTI) and any local NAAT testing results (RSV, 
influenza, etc), if available.
c.
The investigator and site staff/field worker will ensure the active elicitation and collection of AEs and SAEs through 28 days after vaccination.  From 
28 days after vaccination until the maternal participant completes the study, all SAEs will be collected.  Please see Section 8.3.1 for reporting requirements 
and timelines.
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1.2.4. Schedule of Activities for Infant Participants
Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month Follow-
up 
6-Month Follow-
up 
12-Month 
Follow-up 
18-Month Follow-
up
24-Month Follow-
up
Visit Window (Days)
Birth to 7 Days 
After Birth
28 to 48 Days
After Birth
180 to 210 Days 
After Birth
350 to 378 Days
After Birth
525 to 574 Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic 
Clinic 
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or 
Telephone
Assign infant participant identifier
X
Demography 
X
Collect background factorsb
X
X
X
X
X
X
Collect birth outcome information including 
infant’s birth data and appearance, pulse, 
grimace, activity, and respiration (Apgar) 
score
X
Obtain and record infant’s length, head 
circumference, and weight
X
X
X
X
(if clinic visit)
X
(if clinic visit)
Physical examination including vital signs 
X
Targeted physical examination including vital 
signs 
X
X
X
(if clinic visit)
X
(if clinic visit)
Record immune globulin, monoclonal 
antibodies (eg, Synagis), or blood products 
(eg, whole blood, packed cells)
X
X
X
X
X
X
Review eligibility
X
Cord blood sample (~10 mL) for serologic 
assessmentc
X
Record adverse events, NDCMCs, and serious 
adverse events, as appropriated
X
X
X
X
X
X
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Participants
All Infant Participants
Long-Term Follow-up for Infant 
Participants Enrolled in the First 
Year of the Studya
Visit Number
1
2
3
4
5
6
Visit Description
Birth
1-Month Follow-
up 
6-Month Follow-
up 
12-Month 
Follow-up 
18-Month Follow-
up
24-Month Follow-
up
Visit Window (Days)
Birth to 7 Days 
After Birth
28 to 48 Days
After Birth
180 to 210 Days 
After Birth
350 to 378 Days
After Birth
525 to 574 Days
After Birth
714 to 742 Days
After Birth
Type of Visit
Hospital
Clinic 
Clinic 
Clinic or 
Telephone
Clinic or 
Telephone
Clinic or 
Telephone
Surveillance reminder contact
Contact with the infant participants’ 
parent(s) or legal guardian(s)
approximately every week until Visit 3
From Visit 3, contact with the infant participant’s parent(s) or legal 
guardian(s), approximately every 28 to 35 days until the end of the study
Assessment of MA-RTIse
Assessment of MA-RTI events during 
the active RSV surveillance period as 
detailed in Section 1.2.4.1 of the 
schedule of activities
Assessment of MA-RTI events as detailed in Section 1.2.4.1 of the schedule of 
activities
Abbreviations: MA-RTI = medically attended respiratory tract illness; NDCMC = newly diagnosed chronic medical condition; RSV = respiratory syncytial virus.
a.
Applicable only for infant participants enrolled during the first year of the study.
b.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV illness. 
c.    Cord blood must be obtained on the day of birth. Cord blood is collected from the umbilical cord vein attached to the placenta after the umbilical cord has 
been clamped and cut. If cord blood is unavailable, a blood sample may be collected from the infant participant preferably within the first 24 hours but up to 
7 days after birth. The infant’s weight must be used to determine the volume of blood that can be collected.
d.    The investigator and site staff/field worker will ensure the active elicitation and collection of AEs, NDCMCs, and SAEs through 28 days after birth.  From 
29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected.  An NDCMC is defined as a disease or medical 
condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
e.    A confirmed MA-RTI is defined as an expected study event based on the assessments detailed in the schedule of assessment in Section 1.2.4.1. These events 
will not be captured as safety events, unless the investigator or an appropriate designee deems them to be related to the investigational product.
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1.2.4.1. Schedule of Activities for Infant Participants: Medically Attended Respiratory Tract Illness Assessment Visits During 
the Study 
Visit Description
MA-RTI Assessments During the Active RSV 
Surveillance Perioda
MA-RTI Assessmentsb
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed MA-RTI 
and Within 72 Hours
As Soon as Possible After Confirmed MA-RTI 
and Within 72 Hours
Type of Visit
Hospital, Home, or Clinic
Hospital, Home, Clinic, or Telephone
Surveillance reminder contact
Contact the infant participants’ parent(s) or legal 
guardian(s) approximately every week until Visit 3
From Visit 3, contact the infant participants’ parent(s) or 
legal guardian(s), approximately every 28 -35 days until the 
end of the study
Record confirmed MA-RTI as detailed in Appendix 6, as 
appropriate
X
X
Record details of the RTI, including 1 or more of the 
following RTI signs and symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid 
breathing for any duration

Cough

Inability to feed for any duration because of respiratory 
symptoms

Apnea

Any other respiratory symptom of concern 
X
X
In the event that the MA-RTI involved hospitalization, 
assess the details of hospitalizations due to RTI and assess 
whether the event meets the definition of a severe 
MA-LRTIc
X
Perform an in-person study visit and record vital signs and 
targeted physical examination results (heart rate, respiratory 
rate, SpO2, chest wall indrawing)
X
X
(for hospitalized RTIs or severe MA-LRTIs only)
Record local NAAT testing results, if performed and 
availabled
X
X
Collect nasal swab (for RT-PCR)e
X
X
(for hospitalized RTIs or severe MA-LRTIs only)
Collect background factors associated with MA-RTIf
X
X
Record immune globulins, monoclonal antibodies (eg, 
Synagis) or blood products (eg, whole blood, packed cells)
X
X
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Visit Description
MA-RTI Assessments During the Active RSV 
Surveillance Perioda
MA-RTI Assessmentsb
Assessment Period During the Study
Birth to 180 Days After Birth
181 Days After Birth to the End of the Study
Visit Window (Days)
As Soon as Possible After Confirmed MA-RTI 
and Within 72 Hours
As Soon as Possible After Confirmed MA-RTI 
and Within 72 Hours
Type of Visit
Hospital, Home, or Clinic
Hospital, Home, Clinic, or Telephone
Record concomitant medication associated with the 
treatment of the MA-RTI
X
X
Record adverse events, NDCMCs, and SAEs, as 
appropriateg
X
X
Obtain standard-of-care records and complete CRFh
X
X
Compile MA-RTI visit source documentationi
X
X
(for hospitalized RTIs or severe MA-LRTIs only)
Abbreviations: CRF = case report form; ICU = intensive care unit; IV = intravenous; MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically 
attended respiratory tract illness; NAAT = nucleic acid amplification technology; NDCMC = newly diagnosed chronic medical condition; RSV = respiratory syncytial 
virus; RTI = respiratory tract illness; RT-PCR = reverse transcription–polymerase chain reaction; SpO2 = oxygen saturation.
a.
If the infant participant is reported to be experiencing or has had an MA-RTI from birth until Visit 3, the site should arrange a study visit as soon as possible and within 
72 hours. Ideally, the MA-RTI assessment visit will be conducted at the investigational study site; however, it is possible that the visit could be conducted in another 
healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit where the infant participant is residing. 
b.
If the infant participant is reported to be experiencing or has had an RTI associated with severe LRTI criteria or been hospitalized for an RTI from Visit 3 until the end 
of study participation, the site should arrange a visit as soon as possible and within 72 hours of site awareness. Ideally, assessment of these potential endpoint events 
(hospitalization due to RTI or severe MA-LRTI) will be conducted at the investigational study site; however, it is possible that the visit could be conducted in another 
healthcare setting (for example, if the infant participant is hospitalized) or the site staff may visit where the infant participant is residing. 
Note: For nonsevere MA-RTIs, a telephone contact with the infant participants’ parent(s) or legal guardian(s) is acceptable to complete the assessment visit.
c.
Hospitalization due to an RTI and severe MA-LRTI endpoint definitions are detailed in Table 1.
d.
The site staff/field worker will review and collect data related to any local NAAT testing results, if performed and available.
e.
The site staff/field worker will collect nasal swabs for confirmed MA- RTIs, including confirmed cases of hospitalizations due to an RTI and severe MA-LRTIs, within 
72 hours after the event is reported.
f.
Background factors as detailed in Appendix 5 related to socioeconomic and health factors that may impact the incidence of RSV. This will be collected for all MA-RTI 
events reported.
g.    The investigator and site staff/field worker will ensure the active elicitation and collection of NDCMCs and SAEs through the end-of-study visit for the infant 
participant. From 29 days after birth until the infant participant completes the study, NDCMCs and SAEs will be collected. An NDCMC is defined as a disease or 
medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma). Note: A confirmed MA-RTI will not be 
captured as a safety event, unless the investigator or an appropriate designee deems it to be related to the investigational product.
h   Obtain case records, including details of hospitalization, ICU, use of oxygen, IV fluids usage, etc.
i.   Documents to be submitted upon request to the adjudication committee.
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2. INTRODUCTION
Prevention of RSV disease in young infants is a significant unmet medical need globally.  
RSV is the leading cause of bronchiolitis and viral pneumonia in infants and can lead to fatal 
respiratory distress, especially in those with risk factors including premature infants with 
underlying cardiopulmonary disease, or in the absence of effective healthcare systems.1
However, most cases of RSV disease occur in healthy, full-term infants without risk factors.2
Worldwide, RSV kills approximately 118,200 children annually, with about half of those 
deaths occurring in infants under 6 months of age, and the majority of those occurring in 
resource-limited countries.3,4 In the United States, RSV is the leading cause of infant 
hospitalization, with more than 60,000 hospitalizations of children 12 months of age and 
younger annually.5,6  There is increasing evidence that the link between severe RSV disease 
in infancy and wheezing later in childhood may be causal.7,8  Like influenza, RSV infection 
follows a seasonal pattern, causing illness primarily in the cooler months of the year in 
temperate regions and during the wet season in tropical countries with seasonal rainfall.9  
Infection is essentially universal by the time children reach 2 years of age.10
Currently, there is neither specific treatment for RSV infection nor a vaccine to protect 
against RSV disease.  Treatment consists primarily of supportive care.  A prophylactic 
humanized monoclonal antibody, palivizumab (Synagis, AstraZeneca), targeting the RSV F 
glycoprotein is available for prevention of severe RSV disease in young infants at increased 
risk.11  Limitations of its use include its high cost12 and requirement of multiple monthly 
injections,13 and so it remains recommended for use only in very premature infants and 
others at increased risk of severe illness.6,14
Nevertheless, the protective effect of Synagis provides definitive proof of principle that 
serum neutralizing antibody directed against the F protein can provide clinically meaningful 
protection against RSV lower respiratory tract disease in young infants.15  Furthermore, it is 
well known that in other disease settings, antibodies transferred from mothers to their fetuses 
across the placenta can reduce infant disease early in life,16,17,18,19,20,21 suggesting that 
maternal immunization is a reasonable approach to RSV disease prevention among young 
infants.
There are 2 antigenic variants of RSV, namely, RSV subgroup A (RSV A) and RSV 
subgroup B (RSV B).  The RSV vaccine being investigated in this study is a bivalent vaccine 
composed of stable RSV prefusion F antigens representing the 2 subgroups to help ensure the 
broadest coverage against RSV illness.
RSVpreF is a prophylactic vaccine being developed to prevent medically attended
RSV-associated LRTI in infants by active immunization of pregnant women.
2.1. Study Rationale 
There is a large unmet medical need that could be addressed by an effective RSV prophylaxis 
in infancy. Given a global burden of disease in the millions of cases each year, maternal 
immunization offers an attractive strategy for infant disease prevention.  Both preclinical 
studies in animals and interim data from a Phase 1/2 study in healthy nonpregnant adults 
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have demonstrated acceptable tolerability and safety of RSVpreF.  A robust immune 
response has also been observed in the population of the aforementioned trial, at 1 month 
after vaccination. The combined RSV A and B serum neutralization geometric mean titers 
(GMTs) have been shown to be 12 to 20 times higher than those with 100 μg/mL of
palivizumab, the concentration of the monoclonal antibody that is known to provide near to 
complete protection of high-risk infants from severe RSV disease.22,23 RSVpreF is currently 
under assessment in healthy pregnant women 18 through 49 years of age (Study C3671003, 
A Phase 2b, Randomized, Placebo-Controlled, Observer-Blinded Trial to Evaluate the 
Safety, Tolerability, and Immunogenicity of an RSV Vaccine in Pregnant Women 18 Through 
49 Years of Age and Their Infants; ClinicalTrials.gov identifier: NCT 04032093).
This randomized, double- or observer-blinded, placebo-controlled Phase 3 study is designed 
to evaluate the efficacy and safety of maternal immunization with RSVpreF against 
medically attended RSV-associated LRTI in infants.  
2.2. Background 
RSV is an important cause of morbidity and mortality worldwide, with a substantial burden 
of disease borne by young infants.  Rates of severe RSV illness are highest in infants 
6 months of age, with a peak in hospitalization between 1 and 2 months of life, though the 
highest case-fatality rates are observed in the neonatal period (<1 month).2 Infants born 
prematurely and those with underlying cardiac or pulmonary disease are at further increased 
risk of severe clinical disease due to RSV.  A 2017 retrospective case analysis that examined 
RSV mortality data from 23 countries demonstrates the global nature of the seriousness of 
RSV disease, with significant morbidity and mortality occurring in both lower- and middle-
income countries (LMICs) and high-income countries.3,4
No specific treatments for RSV exist, and available prophylactic measures (ie, RSV 
monoclonal antibody) are limited to use in only those infants at highest risk; additionally, in 
LMICs, use of available RSV prophylaxis is cost-prohibitive.  While active immunization 
against RSV in infants might be an option, multiple efforts, extending over half a century, to 
develop a safe and effective RSV vaccine to protect infants from disease have yielded little 
success.  The early peak of disease presents a further obstacle to an active vaccination 
strategy for infants.  Given these challenges, maternal immunization to protect infants early 
in life offers an attractive strategy for infant disease prevention.  
The present RSV vaccine efforts were initiated in early 2014 based on a new scientific 
discovery (determination of the RSV prefusion F crystal structure)24 and a changing 
regulatory and policy environment that today supports the development of vaccines for 
maternal immunization to protect very young infants.  The trimeric RSV F surface 
glycoprotein in a prefusion conformation is now known to be the primary target of 
neutralizing antibodies and is the basis for the engineered antigens in Pfizer’s vaccine 
candidate.   Applying structure-guided vaccine design, Pfizer has developed a stabilized RSV 
prefusion F vaccine candidate.  The core hypothesis underlying Pfizer’s RSV vaccine 
development effort for prevention of infant disease is that vaccine antigens based on RSV 
prefusion F, when administered to pregnant women in the second or third trimester of 
pregnancy, will elicit sufficiently high neutralizing antibody titers that, when the antigens are 
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actively transferred transplacentally to the fetus, will protect infants against RSV disease. 
The aim is for neutralizing antibody levels to be at sufficient levels such that infants will be 
protected from birth and possibly through their first RSV season.
2.3. Benefit/Risk Assessment
RSVpreF is being evaluated in ongoing clinical studies.  Pfizer’s maternal immunization 
approach circumvents the risk of vaccine-mediated disease enhancement that was observed 
in the 1960s following direct immunization of RSV-naive infants with a formalin-inactivated 
RSV vaccine (FI-RSV).25  FI-RSV elicited a predominantly nonneutralizing antibody 
response and a Th2-biased cell-mediated response, both of which are considered potential 
contributing factors to disease enhancement.26  During preclinical studies, in a standard 
cotton rat infectious RSV challenge model, FI-RSV showed pathological signs of causing 
disease enhancement, and the current Pfizer vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease enhancement has not been reported to occur in 
RSV-experienced individuals after immunization with any RSV vaccine candidate.  Because 
pregnant women are universally RSV-experienced, they are not at risk for a 
disease-enhancing immune response to the vaccine that could exacerbate infection in 
themselves or their infants.  A previous study of maternal immunization with a Wyeth (later 
merged with Pfizer) investigational RSV vaccine (PFP-2) showed an acceptable safety 
profile, even though this candidate contained a postfusion RSV F antigen that elicited a 
relatively weak RSV-neutralizing antibody response and a higher nonneutralizing 
RSV-binding antibody response in pregnant women.27  A recently completed Phase 3 
maternal RSV trial (Novavax) with an RSV vaccine containing F not stabilized in the 
prefusion form, given to over 4600 healthy pregnant volunteers, showed a similar safety 
profile in the RSV vaccine and placebo groups.28
Vaccination with the RSV prefusion F antigens elicits a higher ratio of neutralizing to 
nonneutralizing antibodies, more closely matching the profile in naturally exposed 
individuals.  The safety profile of RSVpreF observed to date is similar to that of prior RSV F 
subunit vaccines tested in RSV-experienced adults.
There are limited data on the global burden of maternal RSV infection, likely in part because 
of infrequent diagnostic testing. However, in one multisite study, RSV-associated disease in 
pregnancy was shown to result in prolonged hospitalization and an increased likelihood of 
preterm birth in women who tested RSV-positive.29 It is possible that vaccination may 
benefit the pregnant women who receive it. RTI in mothers who receive RSVpreF will be 
explored in this study.  The benefit of maternal vaccination is accrued to the infant by means 
of transplacental antibody transfer.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the investigator’s brochure (IB), which is the 
single reference safety document (SRSD) for this study. 
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Infant Participants
The study objectives and endpoints for infant participants employ the event definitions in 
Table 1.
Table 1.
Endpoint Events and Definitions in Infant Participants
Study Endpoints/Assessments
Study Definitions
Medically attended visit
Infant participant has been taken to or seen by a healthcare provider (eg,
outpatient or inpatient visit, emergency room, urgent care, or home visit)
MA-RTI visit for infant 
participant
A medically attended visit AND 1 or more of the following RTI signs and 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any 
duration

Cough

Inability to feed for any duration because of respiratory symptoms

Apnea

Any other respiratory symptom of concern 
RSV-positive testa

RSV RT-PCR–positive test result by Pfizer central laboratory
OR

RSV-positive test result by certified laboratory with NAAT for RSV
MA-RTI due to RSVb

An MA-RTI visit 
AND

RSV-positive test result as described in Section 8.1.1.1.
MA-LRTI due to any cause

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age], 
≥50 bpm for ≥2 months to 12 months of age, or ≥40 bpm for ≥12 months 
to 24 months of age) OR

SpO2 <95% OR

Chest wall indrawing
MA-LRTI due to RSVb

Infant with an MA-RTI visit 
AND

Fast breathing (RR ≥60 bpm for <2 months of age [<60 days of age] or 
≥50 bpm for ≥2 to 12 months of age, or ≥40 bpm for ≥12 months to 
24 months of age) OR

SpO2 <95% OR

Chest wall indrawing 
AND 

RSV-positive test result as described in Section 8.1.1.1.
Hospitalized RTI due to RSVb
An RTI due to RSV that results in hospitalization
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Table 1.
Endpoint Events and Definitions in Infant Participants
Study Endpoints/Assessments
Study Definitions
Severe MA-LRTI due to RSVb

Infant with an MA-RTI visit
AND

Fast breathing (RR ≥70 bpm for <2 months of age [<60 days of age], 
≥60 bpm for ≥2 months to 12 months of age, or ≥50 bpm for ≥12 months 
to 24 months of age) OR

SpO2 <93% OR

High-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive) OR

ICU admission for >4 hours OR

Failure to respond/unconscious 
AND

RSV-positive test result as described in Section 8.1.1.1
Protocol-defined primary 
endpoint

Any MA-LRTI or severe MA-LRTI due to RSV as determined by an 
EAC
Abbreviations: bpm = breaths per minute; EAC = endpoint adjudication committee; ICU = intensive care unit; 
MA-LRTI = medically attended lower respiratory tract illness; MA-RTI = medically attended respiratory tract 
illness; NAAT = nucleic acid amplification technology; RR = respiratory rate; RSV = respiratory syncytial 
virus; RTI = respiratory tract illness; SpO2 = oxygen saturation.
a.
RSV-positive testing is defined as a positive RSV test (see Section 8.1.1.1) conducted on a sample obtained 
during the medically attended visit or within 10 days (where Day 1 is the day after the MA-RTI visit) as 
detailed in Section 8.11.7.
b.
The EAC will determine if the endpoint criteria have been met upon review of the site source from the MA-
RTI visit data collected at the study assessment visit, including RSV testing. 
Study Objectives – Infant Participants
Primary Efficacy Objectives –
Infant Participants
Estimands
Primary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTI due to 
RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
RSV-positive MA-LRTI as confirmed by 
the EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth, if 
the analysis at 90 days meets efficacy 
criteria. 

occurring within 150 days after birth, if 
the analysis at 120 days meets efficacy 
criteria.

occurring within 180 days after birth, if 
the analysis at 150 days meets efficacy 
criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Severe MA-LRTIs due to RSV as 
confirmed by the EAC:   

occurring within 90 days after birth.

occurring within 120 days after birth, if 
the analysis at 90 days meets efficacy 
criteria.

occurring within 150 days after birth, if 
the analysis at 120 days meets efficacy 
criteria.

occurring within 180 days after birth, if 
the analysis at 150 days meets efficacy 
criteria.
Primary Safety Objective –
Infant Participants
Estimand
Primary Safety Endpoints –
Infant Participants
To describe the safety of 
RSVpreF.

In infant participants born 
to maternal participants 
receiving 1 dose of 
investigational product, 
the percentage of
participants with each 
safety endpoint in each 
vaccine group.

Specific birth outcomes.

AEs from birth to 1 month of age.

SAEs and NDCMCs:
o
from birth through 6 months of age 
(first RSV season for all infant 
participants).
o
from birth through 12 months of 
age (for all infant participants).
o
from birth through 24 months of 
age (for infant participants born to 
maternal participants enrolled 
during the first year of the study).
Secondary Efficacy Objectives –
Infant Participants
Estimands
Secondary Efficacy Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
Hospitalization due to RSV:

occurring within 90 days after birth.

occurring within 120 days after birth, if 
the analysis at 90 days meets efficacy 
criteria.

occurring within 150 days after birth, if 
the analysis at 120 days meets efficacy 
criteria.

occurring within 180 days after birth, if 
the analysis at 150 days meets efficacy 
criteria.
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To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause MA-LRTI.
VE, defined as the relative risk 
reduction of the endpoint in the 
RSV vaccine group compared 
to the placebo group, for infant 
participants born to maternal 
participants receiving 1 dose of 
investigational product and in 
compliance with the key 
protocol criteria (evaluable 
participants).
MA-LRTI due to any cause with protocol-
defined criteria:

occurring within 90 days after birth.

occurring within 120 days after birth, if 
the analysis at 90 days meets efficacy 
criteria.

occurring within 150 days after birth, if 
the analysis at 120 days meets efficacy 
criteria.

occurring within 180 days after birth, if 
the analysis at 150 days meets efficacy 
criteria.
Exploratory Objectives –
Infant Participants
Estimands
Exploratory Endpoints –
Infant Participants
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-RTI due to 
RSV.
RSV-positive MA-RTI as confirmed by the 
EAC: 

occurring within 90 days after birth.

occurring within 120 days after birth.

occurring within 150 days after birth.

occurring within 180 days after birth.

occurring 181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of hospitalization due to 
RSV.
Hospitalization due to RSV occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of severe MA-LRTI 
due to RSV in infants after 
6 months of age.
Severe MA-LRTIs due to RSV occurring 
181 to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of all-cause MA-LRTI.
MA-LRTIs due to any cause occurring 181 
to 730 days after birth.
To evaluate the efficacy of 
RSVpreF in reducing the 
incidence of MA-LRTIs due to 
RSV A and the incidence of 
MA-LRTIs due to RSV B.
RSV subgroup A– and subgroup B–specific 
MA-LRTI as confirmed by the EAC
occurring within 181 days after birth.
To describe the non-RSV 
infectious etiology of MA-RTI in 
the study population.
Positivity for non-RSV respiratory 
pathogens obtained at unplanned MA-RTI
visits occurring within 181 days after birth.
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To evaluate RSV-neutralizing 
antibody titers elicited by 
RSVpreF and transferred 
transplacentally.
RSV A– and RSV B–neutralizing antibody 
titers measured at birth.
To assess the impact of RSVpreF 
on RSV illness based on 
socioeconomic factors.
Primary and secondary efficacy by select 
demographic risk factors (eg, breastfeeding, 
maternal smoking, number of household 
members).
To assess the effect of RSVpreF 
on healthcare utilization.
Mean/median composite score summarizing 
healthcare utilization, which may include 
the following: number and type of medical 
visits, length of hospital stay, requirement 
for mechanical ventilation, requirement for 
respiratory diagnostic procedures, 
requirement for IV fluids, requirement for 
prescriptions, and antibiotic use.
3.2. Maternal Participants
The study objectives and endpoints for maternal participants employ the event definitions in 
Table 2.
Table 2.
Endpoint Events and Definitions in Maternal Participants
Study Endpoints/Assessments
Study Definitions
Maternal medically attended visit
The maternal participant reports a visit with a healthcare 
provider (outpatient or inpatient visit, emergency room, 
urgent care, or home visit)
MA-RTI visit maternal participant
A medically attended visit AND 1 or more of the following 
RTI signs and symptoms:

New or increased sore throat 

New or increased cough 

New or increased nasal congestion 

New or increased nasal discharge 

New or increased wheezing

New or increased sputum production 

New or increased shortness of breath
Abbreviations: MA-RTI = medically attended respiratory tract illness; RTI = respiratory tract illness.
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Study Objectives – Maternal Participants
Primary Safety Objective –
Maternal Participants
Estimands
Primary Safety Endpoints –
Maternal Participants
To describe the safety and 
tolerability of RSVpreF.
In maternal participants 
receiving 1 dose of 
investigational product, the 
percentage of maternal 
participants with each safety 
endpoint in each vaccine 
group.
The incidence of:

prespecified local reactions within 
7 days after vaccination.

prespecified systemic events within 
7 days after vaccination.

AEs from the time of vaccination 
through 1 month after vaccination.

SAEs throughout the study (Visit 1 
through the 6-month-postdelivery study 
visit).
Exploratory Objectives –
Maternal Participants
Estimands
Exploratory Endpoints –
Maternal Participants
To describe MA-RTI in this 
study population.
The incidence of all-cause MA-RTIs from 
vaccination up to 180 days after delivery.
To evaluate the immune 
responses elicited by 
RSVpreF.

RSV A– and RSV B–neutralizing 
antibody titers and preF IgG titers 
measured:

before vaccination.

at delivery.
3.3. Protocol-Defined Efficacy Endpoints 
All infant participants experiencing an MA-RTI will have an RTI assessment visit as detailed 
in Section 8.1.  This protocol will use an independent EAC to determine whether certain 
investigator-reported events meet the definition of disease-related efficacy endpoints, using 
predefined endpoint criteria as summarized in Table 1. Members of this EAC will be blinded 
to the vaccine assignment to allow for unbiased assessments.
Recognizing that RSV disease is a dynamic illness, sites will be instructed to submit all 
available source documentation for adjudication from the MA-RTI visit and to record data 
from the worst day of illness in the electronic case report form (eCRF).  The EAC will 
determine if the endpoint criteria have been met upon review of the site source
documentation from the MA-RTI visit, including data collected at the study visit, and all 
available RSV testing.  Further information about the EAC will be detailed in the 
adjudication charter, including specific descriptions of the scope of its responsibilities and 
the process and definitions to review and assess study endpoints.
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition and 
constitute a study endpoint will not be recorded as AEs.  For those SAEs that are handled as 
disease-related efficacy endpoints (which may include death), a data monitoring committee 
(DMC) will conduct unblinded reviews on a regular basis throughout the trial (see the Data 
Monitoring Committee section). 
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Nonendpoint events (eg, an event that is determined not to be an MA-RTI) must be evaluated 
for safety reporting as per the protocol requirements.  Any SAE that is adjudicated by the 
EAC not to meet endpoint criteria is reported back to the investigator site of incidence; the 
investigator at the site must evaluate and report that SAE to Pfizer Safety, in accordance with 
the time frames described in Appendix 2 of this protocol.  The investigator’s SAE awareness 
date in this instance is identified as the date on which the investigator site of incidence 
receives the nonendpoint SAE back from the EAC.  Handling these SAEs in this manner will 
allow Pfizer to meet its sponsor reporting obligations to regulatory authorities upon receipt of 
such SAEs.
However, when the investigator has judged the SAE to have a causal relationship with the 
investigational product, the investigator must additionally report the event to Pfizer Safety as 
described in Appendix 2, even if that event is a component of the endpoint.
Any events that remain unadjudicated at the annual safety report cutoff date will not be 
included in the safety tables of the report.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, multicenter, randomized, double- or observer-blinded, placebo-controlled 
study to assess the efficacy, safety, and immunogenicity of bivalent RSVpreF or placebo 
(1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well 
as the safety and immunogenicity in the pregnant women.  This will be a global study, 
including sites in both the northern and southern hemispheres, and it will span multiple RSV 
seasons. 
This is an event-driven study with a target of 124 adjudicated (primary-endpoint) cases of 
MA-LRTI due to RSV (meeting the case definition in the per-protocol infant population 
described in the statistical analysis (Section 9.2). There is no specific case target for the 
additional primary endpoint of severe MA-LRTI. The total enrollment number of maternal 
participants may vary depending on the incidence rate of the primary endpoint in the infant 
participants, true underlying VE, and a potential early stop for efficacy or futility. In the 
event that efficacy in the infant population is demonstrated at the interim analysis, enrollment 
of maternal participants may continue in order to obtain safety evaluations in an adequate 
number of maternal and infant participants to support vaccine registration with national 
health authorities. 
Based on these considerations, and in order to accumulate endpoint cases, vaccination of 
maternal participants will occur at a time of year such that the infant is likely to be exposed 
to seasonal RSV during the first 6 months of life.  It is anticipated that approximately 
6900 mother-infant pairs may be needed to accumulate 124 per-protocol cases.
Study-eligible pregnant women will be randomized in a 1:1 ratio to receive RSVpreF or 
placebo.  For the RSV vaccine group, a single dose and formulation of RSVpreF will be 
selected based on data from the maternal C3671003 study (A Phase 2b, Randomized, 
Placebo-Controlled, Observer-Blind Trial to Evaluate the Safety, Tolerability, and 
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Immunogenicity of a Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women 18 
Through 49 Years of Age and Their Infants. ClinicalTrials.gov identifier: NCT 04032093).  
The selected dose of RSV prefusion F antigen in RSVpreF will be 120 µg (60 µg A and 
60 µg B) or 240 µg (120 µg A and 120 µg B). The selected formulation will be with or 
without Al(OH)3. 
Once they have provided informed consent, the women will be referred to as “maternal 
participants” and will be followed from vaccination during pregnancy until 6 months after 
delivery.  Assessments will include parameters to allow descriptions of safety, tolerability, 
and immunogenicity of the vaccine in maternal participants.  
Infants born to women who receive RSVpreF or placebo in their second or third trimester
will be referred to as “infant participants”. Infant participants born to women enrolled during 
the first year of the study will have 6 scheduled study visits during their 24 months of 
participation, whereas all other infant participants will have up to 4 scheduled study visits 
during their potential 12 months of participation.  For all infant participants, data will be 
collected for any medically attended respiratory illness to assess for cases of LRTI due to 
RSV (efficacy endpoint). Additionally, throughout the study all respiratory illnesses, SAEs, 
and NDCMCs reported will be assessed in this population. For infant participants enrolled 
during the first year of the study, the extended 12-month study duration will involve 
longer-term RTI surveillance and safety oversight to address safety and the possibility of 
conferred enhanced protection (antibody persistence) during a second RSV season. 
All MA-RTIs meeting the protocol definition for a potential study endpoint will be 
adjudicated by an independent adjudication committee. In addition, this study will use an 
E-DMC to monitor vaccine safety and efficacy and study futility.  
4.1.1. Approximate Duration of Participation for Each Participant
Pregnant women will participate in the study from enrollment during their pregnancy, and for 
approximately 6 months after delivery of their infants.  The total duration will be up to 
approximately 10 months, depending on GA at the time of vaccination and when the infant is 
actually born. 
All eligible infant participants born to enrolled maternal participants during the first year of 
the study will participate in the study from the time of birth and will be followed for up to 
24 months for RSV surveillance and safety for the secondary and exploratory endpoints of 
the study. All other infants will participate from the time of birth and for at least 12 months 
after birth. 
4.1.2. Approximate Number of Participants
Healthy pregnant women will be randomly assigned to a study intervention. It is anticipated 
that approximately 6900 mother-infant pairs may be needed to accumulate 124 per-protocol 
cases as defined in Section 9.2 of the protocol.  Enrollment will be monitored to ensure that 
participants will be recruited from both the northern and southern hemispheres. Enrollment 
may vary depending on the incidence in the placebo group, the true underlying VE, the 
dropout rate, and a potential early stop for VE or futility.
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4.2. Scientific Rationale for Study Design
Refer to Section 2.1.
4.3. Justification for Dose
The final dose and formulation of RSVpreF that will be selected for use in this study will be 
based on the safety and immunogenicity data from the ongoing C3671003 maternal 
immunization study and the first-in-human (FIH) study C3671001.
The FIH study was designed to describe the safety, tolerability, and immunogenicity of 
6 RSVpreF candidates with bivalent formulations (RSV A and B) at 3 escalating dose levels 
of 60 µg (30 µg A and 30 µg B), 120 µg (60 µg A and 60 µg B), and 240 µg (120 µg A and 
120 µg B) of the RSV prefusion F antigen, with or without Al(OH)3, when administered 
alone or concomitantly with seasonal inactivated influenza vaccine.  The study utilizes a 
sentinel cohort (N=168; Phase 1) and an expanded cohort (N=1014; Phase 2).  Nonpregnant 
female and male study participants of 2 age groups, 18 through 49 years of age and 
50 through 85 years of age, were enrolled into both cohorts.  The age groups are being run in 
parallel. 
A recent interim analysis of participants 18 through 49 years of age, including safety and 
tolerability (n=533) and immunogenicity (n=513) data up to 1 month after vaccination in the 
expanded cohort and additional immunogenicity data up to 3 months after vaccination in the 
sentinel cohort, has shown the RSVpreF candidate to be immunogenic and well tolerated. 
Local reactions and systemic events were noted to be predominantly mild or moderate across 
all doses and formulations, which is consistent with the current safety profile. The safety 
results from this planned interim analysis of healthy male and nonpregnant female 
participants 18 through 49 years of age are consistent with those from the sentinel-cohort 
analysis and indicate that RSVpreF has an acceptable safety profile and is well tolerated.
The immunogenicity results showed that RSVpreF elicited neutralizing titer geometric mean 
fold rises (GMFRs) of 10 to 20, 1 month after vaccination, depending on the formulation. 
Similarly, across all dose levels, with and without Al(OH)3, RSVpreF elicited high 1-month-
postvaccination RSV A and RSV B neutralizing GMTs. Overall, RSVpreF elicited anti–
prefusion F immunoglobulin G1 (IgG1) responses that paralleled the elicited 
RSV-neutralizing responses. The ratio of RSV 50% neutralizing antibody titer GMFRs to 
prefusion RSV F binding IgG1 titer GMFRs (calculated with combined data for subgroups A 
and B) for the sentinel and expanded 18 through 49 years of age cohorts combined ranged 
from 0.62 to 0.76. The IgG1 and neutralization responses were similar in antigen-level dose
response, in equivalence of RSV A titer GMFRs to RSV B titer GMFRs, and in a lack of 
effect of Al(OH)3. 
The high ratio of RSV-neutralizing antibody titer GMFRs to prefusion F–binding titer 
GMFRs elicited by Pfizer’s RSVpreF candidate indicates that most of the elicited antibody 
can neutralize the virus. It is assumed that this reflects the ability of the antibodies to prevent 
RSV disease in immunized participants and, in the case of maternal immunization, prevent 
disease in their infants.
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The primary mechanism for protection of infants by the RSV maternal vaccine is 
neutralization of the virus by transplacentally transferred antibody, which is increased by 
immunization.  Maternal antibody decays exponentially in infants.  Therefore, it is 
anticipated that higher titers of transferred neutralizing antibodies will provide greater levels 
and durations of infant protection.  Results from the C3671001 FIH trial were used to 
determine the doses and formulations that are currently under investigation in the Phase 2b 
maternal immunization study: 120 µg or 240 µg of RSVpreF with or without Al(OH)3. 
These doses are expected to provide the greatest potential level of transplacental antibody 
transfer to infants and, therefore, the greatest potential benefit.  One-month safety, 
tolerability, and immunogenicity results from the C3671003 maternal Phase 2b trial will be 
used to select a single dose and formulation for the Phase 3 study. Availability of these data 
is expected in 2020.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last infant participant in the 
study. The study may also be terminated earlier for efficacy or futility as described in
Section 9.5.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria 
5.1.1. Inclusion Criteria – Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply 
(refer to the investigator site file [ISF] for further eligibility details):
Note: In countries/locales where study procedures used to determine eligibility criteria 
(eg, ultrasound examination, human immunodeficiency virus [HIV] testing, syphilis testing) 
are not performed as part of routine prenatal care, they must be performed as part of this 
clinical trial and reviewed by the investigator or qualified designee within 28 days prior to 
randomization.  Maternal participants must provide informed consent prior to 
performing any procedures, including those that are being done exclusively to meet 
study eligibility criteria.
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Age and Sex:
1. Healthy women 18 and 49 years of age who are between 24 0/7 and 36 0/7 weeks of 
gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, 
who are at no known increased risk for complications. 
Note: GA must be based upon 1 of the following composite criteria based on timing and 
availability of data on the last menstrual period (LMP) and an ultrasound examination 
performed in the first or second trimester.30  The earliest ultrasound data available during 
the current pregnancy should be used to establish GA:
a.
First-trimester data available (data obtained at ≤13 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a first-trimester ultrasound examination.

If there is a discrepancy of >5 days between the LMP-determined GA and an 
ultrasound result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA 
should be determined using the first-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and an 
ultrasound result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, 
then the GA should be determined using the first-trimester ultrasound result.
b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):

The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a second-trimester ultrasound result.

If there is a discrepancy of >7 days between the LMP-determined GA and the 
ultrasound result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >10 days between the LMP-determined GA and the 
ultrasound result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.

If there is a discrepancy of >14 days between the LMP-determined GA and the 
ultrasound result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, 
then the GA should be determined using the second-trimester ultrasound result.
Type of Participant and Disease Characteristics:
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Receiving prenatal standard of care based on country requirements.
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4. Had an ultrasound examination performed at ≥18 weeks of pregnancy with no significant 
fetal abnormalities observed, based on the investigator’s judgment. 
5. Determined by medical history, physical examination, and clinical judgment to be 
appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) 
surface antigen test during this pregnancy and prior to randomization (Visit 1). 
7. Intention to deliver at a hospital or birthing facility where study procedures can be 
obtained. 
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol OR
11. If the maternal participant is illiterate, a thumbprinted informed consent must be 
obtained, which must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process confirming that the maternal participant 
has been informed of all pertinent aspects of the study.
5.1.2. Inclusion Criteria – Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a 
thumbprinted informed consent must have been obtained, which must have been signed 
and dated by an impartial witness who was present throughout the entire informed 
consent process confirming that the maternal participant/parent(s)/legal guardian(s) has 
been informed of all pertinent aspects of the study for herself (maternal participant) and 
her fetus/infant prior to taking part in the study.  
Note: Informed consent will be obtained from the father of the fetus/infant if mandated 
by local requirements. 
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
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5.2. Exclusion Criteria 
5.2.1. Exclusion Criteria – Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Body mass index (BMI) of >40 kg/m2 at the time of the first obstetric visit during the 
current pregnancy.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any related 
vaccine.
4. Current pregnancy resulting from in vitro fertilization.  Participants known to have used 
clomiphene citrate and/or letrozole with or without IUI are permitted.
5. Current pregnancy complications or abnormalities at the time of consent that will 
increase the risk associated with the participation in and completion of the study, 
including but not limited to the following (refer to the ISF for further details):

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.

Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated 
hypothyroidism.  This also includes disorders of glucose intolerance (eg, diabetes 
mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if 
uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the 
investigator’s judgment, that will increase the risk associated with the participation in and 
completion of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks’ gestation.
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
Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or major congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the maternal 
participant’s participation in, and completion of, the study or could preclude the 
evaluation of the maternal participant’s response.
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other 
illness requiring chronic treatment with known immunosuppressant medications, 
including monoclonal antibodies, within the year prior to enrollment.  
9. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to 
consent and/or during study participation.
11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of 
systemic corticosteroids for >14 days within 28 days prior to study enrollment.  
Prednisone use of <20 mg/day for ≤14 days is permitted. Inhaled/nebulized, intra-
articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
12. Current alcohol abuse or illicit drug use.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before 
investigational product administration, or planned receipt through delivery, with 
1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt 
during study participation.
Diagnostic Assessments:
Not applicable.
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Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
5.2.2. Exclusion Criteria – Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
2. Receipt of investigational or approved monoclonal antibodies against RSV.
5.2.3. Temporary Vaccination Delay Criteria – Maternal Participants
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and if no other exclusion criteria are met.  
The prevaccination blood draw and vaccination should take place on the same day.

Current febrile illness (body temperature 100.4F [38C]) or other acute illness within 
48 hours before investigational product administration.

Diagnosed malaria within the last 7 days prior to investigational product administration.

Receipt of any inactivated vaccine within 14 days or any live vaccine within 28 days 
before investigational product administration. 

If systemic corticosteroids (equivalent of ≥20 mg/day of prednisone) have been 
administered short term (≤14 days) for treatment of an acute illness, investigational 
product administration should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
5.3. Lifestyle Considerations
No restrictions are required.
5.4. Screen Failures
Screen failures are defined as maternal participants who consent to participate in the clinical 
study but are not subsequently randomly assigned to investigational product. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. 
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6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
For this study, the investigational product(s) are RSVpreF and placebo (lyophile match).
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine 
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.  
There are 2 presentations of RSV drug product representing 2 dose levels of RSV antigen 
(120 µg and 240 µg).  The drug product is supplied as a lyophilized white cake in a 2-mL 
glass vial, with a 13-mm lyophilization stopper, aluminum overseal, and flip-off cap. The 
drug product is reconstituted by diluent consisting of either sterile water as diluent prefilled 
syringe (PFS) or Al(OH)3 0.4-mg/mL suspension for injection PFS. The lyophilized drug 
product contains excipients that, after reconstitution, will yield a solution as detailed in 
Table 3.
Note: Only 1 dose and formulation of RSVpreF will be selected for use in this study.
The fill volume of the drug product vial and diluent PFS are designed such that the intended 
vaccine dose is delivered in a 0.5-mL injection volume.   
Table 3.
Composition of the RSV Vaccine Intended for Clinical Evaluation After 
Reconstitution With Diluent
Formulation
120-µg Antigen Dose
240-µg Antigen Dose
Without Al(OH)3
(mg/mL)
With Al(OH)3
(mg/mL)
Without Al(OH)3
(mg/mL)
With Al(OH)3
(mg/mL)
847 A DS
0.12
0.12
0.24
0.24
847 B DS
0.12
0.12
0.24
0.24
Tromethamine base 
0.23
0.23
0.23
0.23
Tris-hydrochloride
2.07
2.07
2.07
2.07
Sucrose
22.5
22.5
22.5
22.5
Mannitol
45.0
45.0
45.0
45.0
NaCl
2.19 
5.55
2.19 
5.55
Polysorbate 80
0.15
0.15
0.15
0.15
Al(OH)3
N/A
0.4
N/A
0.4
Abbreviations:  Al(OH)3 = aluminum hydroxide; DS = drug substance; N/A = not applicable; 
NaCl = sodium chloride.
Note: A single dose and formulation of RSVpreF will be selected based on data from the maternal C3671003 
study (NCT: 04032093).
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6.1.2. Placebo
Placebo will be a lyophile match to the vaccine, which will consist of excipients matched to 
those used in the RSVpreF vaccine formulation, minus the active ingredients. 
If the final RSVpreF formulation without Al(OH)3 is selected, the physical appearance of the 
reconstituted RSVpreF and placebo will be matched and the study will be conducted in a 
double-blinded manner.
In the event that the RSVpreF formulation with Al(OH)3 is selected, the reconstituted 
placebo will not contain Al(OH)3. The physical appearance of the reconstituted RSVpreF and 
the placebo will differ, and the study will be conducted in an observer-blinded manner.
The fill volume of the placebo vial and diluent PFS is designed such that the intended 
placebo dose is delivered in a 0.5-mL injection volume.
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
6.1.3. Administration
Maternal participants will receive 1 dose of investigational product at the vaccination visit 
(Day 1) in accordance with the study’s SoA.  The investigational product will be 
administered intramuscularly by injecting the entire contents of the syringe (0.5 mL) into the 
deltoid muscle, preferably of the nondominant arm, unless medically contraindicated, in 
which case the injection may be administered in the dominant arm. Investigational product
administration will be performed by appropriately designated study staff at the investigator 
site.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance. 
Investigational product administration details will be recorded on the case report form (CRF).
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6.1.4. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluents for the RSV
vaccine or placebo, consisting of either sterile water PFS or Al(OH)3 0.4-mg/mL suspension 
for injection PFS.
Instructions for medical device use are provided in the IP manual.
Medical device incidents, including those resulting from malfunctions of the device, must be 
detected, documented, and reported by the unblinded study personnel throughout the study. 
Please refer to Section 8.3.6 for details. 
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention, as applicable for 
temperature-monitored shipments. 
2. Only maternal participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.  At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking days must indicate the minimum and maximum 
temperature since previously documented for all site storage locations upon return to 
business.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).  All study interventions will be 
accounted for using an investigational product accountability form/record.  
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the investigational product manual (IP manual).
5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
6. Study interventions should be stored in their original containers and in accordance with 
the labels.
7. See the IP manual for storage conditions of the study intervention once reconstituted.
8. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken.  The site should actively pursue 
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options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use of 
the study intervention after the temperature excursion. Use of the study intervention prior 
to Pfizer approval will be considered a protocol deviation. Specific details regarding the 
definition of an excursion and information the site should report for each excursion will 
be provided to the site in the IP manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
Additional details about accountability, storage, destruction, and excursion reporting can 
be found in the IP manual.
6.2.1. Preparation and Dispensing
Refer to the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
Investigational product and placebo will be prepared by qualified site personnel according to 
the IP manual.  The investigational product will be administered only to maternal participants 
who are blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Blinding of Study Site Personnel 
This study is a double- or observer-blinded study, as the physical appearance of RSVpreF 
and placebo may differ.
Double-Blinded Study Personnel
If this is a double-blinded study, the physical appearance of RSVpreF and placebo will be 
matched. The maternal participant, investigator, study coordinator, and all site staff will be 
blinded. 
Observer-Blinded Study Personnel
If this is an observer-blinded study, the physical appearance of RSVpreF and placebo will not 
be matched. At the study site, only the dispenser(s)/administrator(s) will be unblinded, but all 
other study personnel, including the investigator and study coordinator, and the maternal 
participant will be blinded.
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Contact between the unblinded dispenser(s)/administrator(s) and maternal participants should 
be kept to a minimum. The investigator, study coordinator, and any site staff other than the 
unblinded dispenser(s)/administrator(s) must not be allowed to know the investigational 
product assigned to any maternal participant and must not be allowed to see the 
investigational product.
Please refer to the IP manual for further details.
6.3.2. Blinding of the Sponsor
The sponsor study team members will be blinded throughout the study to the vaccine 
assignments of all participants enrolled in the study. 
Laboratory personnel performing the serology and virology assays will remain blinded to 
vaccine assigned/received throughout the study.
6.3.3. Allocation to Investigational Product
Allocation of maternal participants to vaccine groups will proceed through the use of an 
interactive response technology (IRT) system (interactive Web-based response [IWR]).  The 
site personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the maternal participant number.  The site personnel will then be 
provided with a vaccine assignment, randomization number, and dispensable unit (DU) or 
container number as investigational product is being supplied via the IRT system.  The IRT 
system will provide a confirmation report containing the maternal participant number, 
randomization number, and DU or container number assigned. The confirmation report must 
be stored in the site’s files. 
Note: Maternal participants will be randomized to a vaccine group as described above.  The 
infants of the maternal participants will be assigned an infant participant number at birth.
Investigational product will be dispensed and administered at study Visit 1 summarized in 
the SoA. 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Maternal participants will be assigned to receive investigational product according to the 
randomization scheme.  Investigators will remain blinded to the investigational product 
assigned to each maternal participant throughout the course of the study. Based on 
observer-blinded considerations for this study, an otherwise uninvolved third party will be 
responsible for the preparation and dispensing of all investigational product and will 
endeavor to ensure that there are no differences in time taken to dispense or visual 
presentation of the investigational products following randomization.
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In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
investigational product records at the site(s) to verify that randomization/dispensing has been 
done accurately.
6.3.4. Breaking the Blind 
The study will be maternal participant and investigator blinded.
At the initiation of the study, the investigator will be instructed on the method for breaking
the blind for an individual participant.  The method will be an electronic process.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the participant.  The 
investigators should make every attempt to contact a member of the sponsor’s study team 
prior to breaking the blind.  When the blinding code is broken, the reason must be fully
documented and entered on the CRF.  
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
6.5. Concomitant Therapy 
6.5.1. Prohibited Concomitant Vaccinations and Treatments – Maternal Participants

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study.

Receipt of blood/plasma products or Ig, from 60 days before investigational product 
administration, or planned receipt through delivery, with 1 exception, Rho(D) immune 
globulin (eg, RhoGAM), which can be given at any time.

Immunosuppressive therapy is prohibited during the course of the study.

Nonstudy vaccines may not be given concomitantly with the investigational product or 
within 7 days after investigational product administration (Day 1 to Day 7), except if 
medically necessary (eg, during an outbreak or pandemic situation).  
6.5.2. Permitted Concomitant Vaccinations and Treatments – Maternal Participants

Licensed vaccines (including influenza vaccine and tetanus, diphtheria, and acellular 
pertussis vaccine [Tdap]) may be given during the study starting 7 days after
investigational product administration (Day 8) as per local recommendation for 
immunization in pregnant women. If medically necessary (eg, during an outbreak or 
pandemic situation), influenza vaccine, Tdap, or other vaccines may be given at any time.
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Note: The restricted timelines around the use of Tdap may be dropped based on data from the 
C3671004 study (A Phase 2b, Placebo-Controlled, Randomized, Observer-Blind Study to 
Evaluate the Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus (RSV) 
Vaccine When Administered Concomitantly With Tetanus, Diphtheria, and Acellular 
Pertussis Vaccine (Tdap) in Healthy Nonpregnant Women 18 Through 49 Years of Age).

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. Prednisone use of <20 mg/day for ≤14 days prior to the administration of 
investigational product is permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during participant participation in the 
study.
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following vaccinations and treatments for maternal participants would require reporting 
in the CRF during the study: 

Details of any vaccinations given at any time during the pregnancy through the final 
study visit will be collected and recorded in the CRF.

Details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]), or blood products 
(eg, whole blood, packed cells) given to the maternal participant at any time during the 
pregnancy or during the study will be collected and recorded in the CRF.

Details of any intrapartum antibiotic prophylaxis (IAP) for maternal group B 
streptococcal (GBS) colonization given to the maternal participant at delivery will 
be collected and recorded in the CRF.

Any prescribed medications taken to treat medically attended respiratory illnesses from 
enrollment until the final study visit will be recorded in the CRF.
Concomitant medications not meeting the criteria above will be assessed but not documented 
on the CRF.
6.5.4. Permitted Concomitant Vaccinations and Treatments – Infant Participants

Routine treatments, routine vaccinations, and routine procedures 
(eg, circumcision) are permitted at any time according to national recommendations or 
medical standard of care or accepted practice.

Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during infant participant participation in the study.

Local anesthetic may be applied to the site of the blood draw, as appropriate.
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6.5.5. Recording Nonstudy Vaccinations and Concomitant Medications – Infant 
Participants
The following CRF reporting guidelines are applicable to treatments given to infant 
participants during the study:

Details of any Ig (including monoclonal antibodies [eg, Synagis] or immune globulin 
[eg, hepatitis B immune globulin (HBIG)]) or blood products (eg, whole blood, packed 
cells) given to the infant participant will be collected from the time of birth until the final 
study visit and recorded in the CRF.

Any prescribed medication taken to treat medically attended respiratory illnesses from 
the time of birth until the final visit.  

Details of IV fluids given during an MA-RTI will be collected and recorded in the CRF.
6.6. Dose Modification 
Dose modification is not applicable in this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Discontinuation of study intervention is not applicable in this study.
7.2. Participant Discontinuation/Withdrawal From the Study 
A maternal participant may withdraw from the study at any time at her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. An infant participant may withdraw from the study at 
any time at the request of his or her parent(s) and/or legal guardian(s) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.
The participants, or, if appropriate, their parent(s) and/or legal guardian(s), should be
questioned regarding their reason for withdrawal. The participant will be permanently
discontinued both from the study intervention and from the study at that time.
If a maternal participant withdraws from the study, she may request destruction of any 
remaining samples, but data already generated from the samples will continue to be available 
and may be used to protect the integrity of existing analyses. If an infant participant is 
withdrawn from the study, his or her parent(s) and/or legal guardian(s) may request 
destruction of any remaining samples, but data already generated from the samples will 
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continue to be available, and may be used to protect the integrity of existing analyses. The 
investigator must document any such requests in the site study records.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Clinical Trial (CT) SAE Report.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
Participants who withdraw after randomization will not be replaced.
7.3. Withdrawal of Consent 
Maternal participants and parent(s)/legal guardian(s) of infant participants born to maternal 
participants who request to withdraw consent from any further study contact or with persons 
previously authorized by the participant to provide this information should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible.  The withdrawal of consent should be explained in detail in the medical records by 
the investigator, as to whether the withdrawal is only from study procedures and/or 
postvaccination study follow-up. In the event that vital status (whether the participant is 
alive or dead) is being measured, publicly available information should be used to determine 
vital status only as appropriately directed in accordance with local law.
7.4. Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant, or parent(s) and/or legal guardian(s), and 
reschedule the missed visit as soon as possible and counsel the participant or parent(s) 
and/or legal guardian(s) on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the participant or parent(s) and/or legal guardian(s) wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods).  These contact attempts should be documented in the participant’s 
medical record.
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
Should the participant or parent(s) and/or legal guardian(s) continue to be 
unreachable, the participant will be considered to have withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is handled as part of 
Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA.  Protocol waivers or
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the maternal participant’s routine clinical 
management and obtained before signing of the ICD may be utilized for baseline 
purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA and protocol.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
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8.1. Efficacy Assessments 
8.1.1. Efficacy Assessments – Infant Participants
MA-RTIs in the infant participant will be identified from birth until the end of the infant’s 
participation in the study.  If the infant participant meets any RTI criteria listed below that 
require a visit by or a visit to a healthcare provider (outpatient or inpatient visit, emergency 
room, urgent care, or scheduled home visit), an RTI assessment visit by the study staff will 
be required (see Section 8.11.7).
The RTI criteria are if the infant experiences 1 or more of the following respiratory signs or 
symptoms:

Nasal discharge for 24 hours or more

Difficulty breathing, labored breathing, or rapid breathing for any duration

Cough

Inability to feed for any duration due to respiratory symptoms

Apnea

Any other respiratory symptom of concern 
Evaluation of these MA-RTI events will be based on predefined clinical signs and symptoms 
and testing criteria (shown in Table 1) obtained at the medically attended visit with the 
healthcare provider and/or the study visit. These events will be assessed and confirmed to be 
contributing to the study endpoints by an independent EAC as per the protocol.
8.1.1.1. Midturbinate Nasal Swab Collection and Testing Requirements for Endpoint 
Confirmation – Infant Participants
Midturbinate nasal swabs will be collected for RSV analyses from infant participants at each 
MA-RTI study visit during the RSV surveillance period from birth until Visit 3, and for all 
hospitalizations due to an RTI and severe cases of MA-LRTI during the RTI surveillance 
period from Visit 3 until the end of the study (see Section 1.2.4.1 and Table 1). The swabs
will be sent to Pfizer for centralized reverse transcription–polymerase chain reaction 
(RT-PCR) testing.
RSV testing performed locally as part of routine care will be considered valid when analyzed 
under the following conditions:  

Nucleic acid amplification technology (NAAT)-based test result positive for RSV was 
obtained using a Food and Drug Administration ( FDA)-cleared assay.
OR
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
NAAT-based test result positive for RSV was obtained using an assay that is not FDA
cleared but was conducted in a laboratory that is currently Clinical Laboratory 
Improvement Amendments (CLIA) certified. 
Note: Rapid antigen-based test results will not be considered for endpoint assessment.
Study samples should be collected as close to the medical visit as possible and preferably 
within 72 hours of the MA-RTI visit. RSV study samples will count toward the endpoint 
definition when collected for up to 10 days after the MA-RTI, where Day 1 is the day after 
the MA-RTI visit. These results will be used for MA-RTI endpoint definition and 
confirmation as detailed in Table 1.
8.1.1.2. Events for Adjudication and Submission Guidance – Infant Participants
To maintain scientific integrity, this protocol will use an EAC for the adjudication of all 
primary efficacy endpoints and death events associated with the infant participants due to any 
cause, as summarized below.  The EAC will remain blinded to the maternal participants’ 
vaccine assignments, and the EAC’s assessment of these events will represent the final 
confirmed endpoint classification of the event. 
The efficacy-related events for adjudication include all MA-RTI events. The study 
definitions for endpoint events and the MA-RTI adjudication criteria for the EAC, including 
roles and responsibilities, are specified in the endpoint adjudication committee charter 
(EACC). 
The identification of an MA-RTI will be made by the investigational site and communicated 
to Pfizer or its designee. However, these MA-RTI events may also be identified by Pfizer or 
its designee during the review of clinical data listings or by site monitors during routine 
monitoring of the infant participants’ study records. Pfizer or its designee will notify the 
investigational site of any events identified during this process.
The EAC is responsible for adjudicating whether MA-RTI events fulfill the protocol-defined 
clinical criteria as a primary endpoint, whether the event was due to RSV based on 
confirmatory testing, and the severity of the illness (eg, MA-RTI, MA-LRTI, or severe 
MA-LRTI).  The EAC will adjudicate all RSV-positive MA-RTI cases through the active 
follow-up period including all cases occurring up to 180 days after birth. The EAC will 
adjudicate severe manifestations of RSV: all RSV-associated cases of hospitalization and 
severe MA-LRTI. All deaths will be adjudicated to determine whether they are related to 
RSV during the course of the study. 
The Pfizer study team or designee will provide a listing of specific documents needed to 
support endpoint adjudication by the EAC. These documents will be detailed in the EACC
and the ISF.  Obtaining and submitting the documentation, including results of local testing 
for RSV, will be the responsibility of the investigational site. Documentation will vary based 
on the potential endpoint requiring adjudication and may include (but not be limited to) 
emergency room visit records, hospital discharge summaries, clinic and/or progress notes, 
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diagnostic tests, pathology reports, autopsy reports, and death certificate information, as 
applicable.
Pfizer may request that additional cases of interest be reported to the committee in addition to 
those listed above, including cases in which RSV testing is indeterminant or otherwise 
unclear. Cases that are determined to be RSV positive using non–NAAT-based clinical 
testing can be adjudicated, explored, and summarized descriptively.
8.1.2. Exploratory Efficacy Assessments – Maternal Participants
An MA-RTI will be identified from vaccination until the end of the study and will contribute 
to an exploratory endpoint for maternal participants.  The definition and assessment criteria 
as described in Section 8.10.6 include a visit by or to a healthcare provider (outpatient or 
inpatient visit, emergency room, urgent care, or home visit) for any symptoms in the RTI 
criteria as detailed in Table 2.
The maternal participant should contact the study staff immediately but no later than the next 
scheduled visit to report RTI signs and symptoms for which she sought medical attention. 
The procedures as detailed in Section 1.2.3.1 and Section 8.10.6 will be required to capture 
the event in the CRF.
8.1.3. Efficacy Endpoints and Safety Reporting Requirements – Maternal and Infant 
Participants
MA-RTI events that are consistent with the clinical and RSV testing endpoint definition for 
infant participants and have been adjudicated as a study endpoint (primary or secondary) by 
the EAC should not be recorded as AEs. These data will be captured as efficacy assessment 
data only, as these are expected endpoints.  
For maternal participants, MA-RTI events that are consistent with the clinical and endpoint 
definition will be captured as detailed in Section 8.1.2 and will not be recorded as AEs.  
Any SAE that the investigator has judged to have a causal relationship with the 
investigational product MUST be reported to Pfizer Safety as described in Appendix 2, 
even if that event is a component of an endpoint.
8.1.4. Immunogenicity Assessments 
8.1.4.1. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be approximately 30 mL (~15 mL/visit).  
8.1.4.2. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical 
Consideration for Clinical Trials Performed in Children.31
All infants will have a cord blood sample collected at birth. The cord blood is collected from 
the umbilical cord vein attached to the placenta after the umbilical cord has been clamped 
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and cut. Blood should be collected as soon as feasible after birth to minimize coagulation 
and maximize volume. The total volume of cord blood to be collected for antibody 
assessment in this study will be 10 mL. 
If cord blood is unavailable, a blood sample may be collected from the infant participant up 
to 7 days after birth but preferably within 24 hours after birth.  The infant’s weight must 
be used to determine the volume of blood that can be collected (see Table 4).  
A blood sample will be collected from the infant participant only if a cord sample is not
obtained. In the event that a venous sample is collected, the volume of venous blood will 
vary depending on the infant’s weight. 
The maximum volume of blood collected from the infant in the absence of cord blood will be 
no more than 5 mL.
Table 4.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not Obtained
Body Weight (in kg)
Approximate Volume of Blood (in mL) 
to Be Collected 
<1.3
No blood draw
1.3 to ≤2.4
1.0
>2.4 to ≤3.7
2.0
>3.7 to ≤4.9
3.0
>4.9 to ≤6.2
4.0
>6.2
5.0
8.1.4.3. RSV Vaccine Antibody Testing – Maternal and Infant Participants
Maternal sera and infant cord blood collected will be assayed for RSV A– and RSV B–
neutralizing titers and anti-RSV prefusion F IgG levels. Maternal sera collected may be 
tested for Ig levels against nonvaccine RSV antigens to assess natural RSV exposure.
RSV A– and RSV B–neutralizing antibody titers will be determined and reported as the 
neutralizing titer. IgG levels will be determined against both RSV A and RSV B prefusion F 
antigens in a direct-binding Luminex immunoassay (dLIA) and reported as an anti–
prefusion F IgG level.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development – Maternal and Infant Participants
Samples remaining after completion of the planned assays from blood draws or respiratory 
nasal swab specimens taken throughout the study may be used for additional vaccine and 
infectious disease related research. Samples may also be used for assay development, 
standardization, qualification, and validation.  This work is critical in the development, 
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qualification, and validation of serological assays and is required by regulatory authorities for 
their use in the licensure of a vaccine.
8.1.4.5. Respiratory Pathogens – Infant Participants
Midturbinate nasal swabs will be collected from infant participants following any MA-RTI
visit during the RSV surveillance period from birth until Visit 3, and for all hospitalizations 
due to an RTI and severe cases of MA-LRTI during the RTI surveillance period from Visit 
3 until the end of the study (see Section 1.2.4.1 and Table 1). 
Samples will be analyzed for RSV A, RSV B, and other respiratory pathogens by polymerase 
chain reaction (PCR)-based assays at a central laboratory. Additional exploratory analyses 
may also be performed.
Sample collection, processing, storage, and shipping information can be found in the ISF or 
equivalent manual.  All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.4.6. Biological Samples – Maternal and Infant Participants
Samples will be used only for scientific research.  Each sample will be labeled with a code so 
that the laboratory personnel testing the samples will not know the maternal or infant
participant’s identity.  Samples that remain after performing assays outlined in the protocol 
may be stored by Pfizer.  Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.  If allowed by the ICD, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No sequencing of the maternal or infant participant’s DNA will be performed. 
The maternal participant may request that her (or her infant’s) samples, if still identifiable, be 
destroyed at any time; however, any data already collected from those samples will still be 
used for this research.  The biological samples may be shared with other researchers as long 
as confidentiality is maintained, and no testing of the maternal and infant participant’s DNA 
is performed.
8.2. Safety Assessments 
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
Safety parameters will be assessed as described in the SoA and below for both maternal and 
infant participants.
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8.2.1. Participant Electronic Diary – Maternal Participants
All maternal participants vaccinated in the study will be observed for at least 30 minutes after 
investigational product administration for any acute reactions. For all maternal participants, 
prespecified local reactions and systemic events will be collected for 7 days after vaccination.  
Maternal participants will be required to use an electronic diary (e-diary), installed on a 
provisioned device or as an application on a personal device, and will be asked to monitor 
and record local reactions, systemic events, and temperature each evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination).  Prior 
to vaccination, a baseline assessment of prespecified systemic events will be recorded in the 
e-diary.
The e-diary allows recording of these assessments only within a fixed time window each day, 
thus providing the accurate representation of the maternal participant’s experience at that 
time.
Similarly, based on local practice in certain countries/locales, a field worker may visit 
maternal participants in their homes daily after vaccination to assess and record local 
reactions, systemic events, and temperature each day (beginning in the morning) for 6 days 
following vaccination (Day 2 through Day 7, where Day 1 is the day of vaccination).  The 
field worker will be required to record these data on a provisioned device or an application 
on a personal device, thus providing the accurate representation of the maternal participant’s 
experience at that time.  For events persisting at Day 7 and use of antipyretic medication 
continuing at Day 7, the field worker will continue to visit the participant and record 
information until resolution.
Data on local reactions, systemic events, and temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via an internet-based 
portal.  At intervals agreed to by the vendor and Pfizer, these data will be transferred 
electronically to Pfizer for analysis and reporting.  These data do not need to be recorded by 
the investigator in the CRF, except the following conditions:

If a maternal participant withdraws because of prompted events recorded in the e-diary, 
the event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF. 
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate maternal participant compliance and as part of the 
ongoing safety review. These prospectively collected occurrences of local reactions and 
systemic events are graded as described in Section 8.2.1.1 and Section 8.2.1.2.
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8.2.1.1. Local Reactions – Maternal Participants
Following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), the 
maternal participants/field worker will be asked to assess redness, swelling, and pain at the 
injection site and to record the symptoms in the e-diary or appropriate device, in the evening
or daily based on local practice.  
Redness and swelling will be measured by the maternal participant/field worker and recorded 
in measuring device units (range: 1 to 20 and 21+) and then categorized during analysis as 
mild, moderate, or severe based on the grading scale in Table 5. Measuring device units can 
be converted to centimeters according to the following scale: 1 measuring device unit = 
0.5 cm.
A maternal participant with severe redness, swelling, or pain at the injection site, necrosis, or 
exfoliative dermatitis will be prompted to contact the investigator to perform an unscheduled 
visit to assess the reaction or will be referred to the appropriate healthcare facility at the 
discretion of the field worker if there are any concerns, as appropriate.  In the event that the 
maternal participant does not call, the investigator or qualified designee will contact the 
maternal participant.
Only an investigator or a qualified designee is able to classify a maternal participant’s local 
reaction as Grade 4, after clinical evaluation of the maternal participant or documentation 
from another medically qualified source (eg, emergency room or hospital record) or, in the 
case of pain at the injection site only, contact with the maternal participant.  If a maternal 
participant experiences a Grade 4 local reaction, the investigator must immediately notify the 
sponsor.  A Grade 4 reaction will be collected as an AE on the CRF.  The event will be 
graded using the AE intensity grading scale (Section 10.2.4).
The site staff/field worker will educate the maternal participant regarding signs and 
symptoms (including necrosis at the injection site or exfoliative dermatitis) that would 
prompt site contact.  
If a local reaction persists beyond the end of the e-diary period, the maternal participant will 
be requested to report that information and/or any new AEs that develop to the investigator,
or the field worker will continue to visit the maternal participant to assess and record the 
information until resolution, as per local practice. The investigator will enter this additional 
information in the maternal participant’s source notes and CRF.
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Table 5.
Grading Scale for Local Reactions
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(>20 measuring 
device units)
Necrosis
Pain (at the 
injection site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a maternal participant’s local reaction as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the injection site only, 
contact with the maternal participant.  Grade 4 local reactions will be collected on the AE case report form 
and assessed by the investigator using the AE intensity grading scale as detailed in Section 10.2.4.
8.2.1.2. Systemic Events – Maternal Participants
Prior to vaccination on Day 1, a baseline assessment of fatigue, headache, vomiting, 
nausea, diarrhea, muscle pain, and joint pain will be recorded in the e-diary. Following 
vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination), maternal 
participants will be asked to assess fatigue, headache, vomiting, nausea, diarrhea, muscle 
pain, and joint pain and to record the symptoms in the e-diary in the evening or, based on 
local practice in certain countries/locales, a field worker will visit maternal participants daily 
after vaccination to assess the presence of systemic events each day (beginning in the 
morning) for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination).  The field worker will record the symptoms in the e-diary daily. The symptoms 
will be assessed by the maternal participant according to the grading scale in Table 6.  
Maternal participants will also be instructed to contact site staff if they visit the emergency 
room or are hospitalized for severe fatigue, headache, vomiting, nausea, diarrhea, muscle 
pain, or joint pain within 7 days after vaccination. Based on local practice in certain 
countries/locales, maternal participants will be referred to the appropriate healthcare facility 
at the discretion of the field worker if there are any concerns, as appropriate. In the event 
that the maternal participant does not call, the investigator or qualified designee will contact 
the maternal participant. The study staff/field worker may also contact the maternal 
participant to obtain additional information on events entered into the e-diary.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic 
event as Grade 4, after clinical evaluation of the maternal participant or documentation from 
another medically qualified source (eg, emergency room or hospital record) or contact with 
the maternal participant.  If a maternal participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor.  Grade 4 reactions will be collected as an 
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AE on the CRF.  The event will be graded using the AE intensity grading scale 
(Section 10.2.4).
Further, if a systemic event persists beyond the end of the e-diary period, the maternal 
participant will be requested to report that information and/or any new AEs that develop to 
the investigator, or the field worker will continue to visit the maternal participant to assess 
and record the information until resolution, as per local practice. The investigator will enter 
this additional information in the maternal participant’s source notes and CRF.
Table 6.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness in 
diaries)
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Headache
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Vomiting
1 to 2 times in 24 hours
>2 times 
in 24 hours
Requires 
intravenous 
hydration
Emergency room 
visit 
or hospitalization 
for severe vomiting
Nausea
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe nausea
Diarrhea
2 to 3 loose stools
in 24 hours
4 to 5 loose stools
in 24 hours
6 or more loose 
stools
in 24 hours
Emergency room 
visit
or hospitalization 
for severe diarrhea
Muscle pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe muscle pain
Joint pain
Does not interfere with 
activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe joint pain
a.
Only an investigator or qualified designee is able to classify a maternal participant’s systemic event as 
Grade 4, after clinical evaluation of the maternal participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the maternal participant.  Grade 4 
systemic reactions will be collected on the AE case report form and assessed by the investigator using the 
AE intensity grading scale as detailed in Section 10.2.4.
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8.2.1.3. Temperature – Maternal Participants
A digital thermometer will be given to the maternal participant with instructions on how to 
measure oral temperature at home.  Temperature will be collected in the evening for 7 days 
following vaccination (Day 1 through Day 7, where Day 1 is the day of vaccination) and at 
any time during the 7 days following vaccination that fever is suspected. Similarly, based on 
local practice in certain countries/locales, the field worker will visit maternal participants 
daily for 7 days after vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination) to collect the temperature.
Fever is defined as an oral temperature of 100.4F (38.0°C). The highest temperature for 
each day will be recorded in the e-diary, where possible. In certain countries/locales, if a 
temperature of 100.4F (38.0°C) is recorded for a maternal participant during the 
collection of diary events after vaccination, the field worker will perform a rapid test for 
malaria as per local practice.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature less than 100.4°F [38.0°C]) in order to 
collect a stop date in the CRF. 
A maternal participant with a fever >102.0F (>38.9°C) will be prompted to contact the 
investigator. Based on local practice in certain countries/locales, maternal participants will 
be referred to the appropriate healthcare facility at the discretion of the field worker if there 
are any concerns, as applicable. In the event that the maternal participant does not call, the 
investigator or qualified designee will contact the maternal participant.  The investigator or 
qualified designee will assess the fever and perform an unscheduled visit as appropriate.
Temperature will be measured and recorded to 1 decimal place and then grouped into ranges 
for the analysis according to Table 7.  Temperatures reported in degrees Fahrenheit will be 
programmatically converted to degrees Celsius for reporting.
Table 7.
Ranges for Fever
Fever
≥38.0C to 38.4C
>38.4C to 38.9C
>38.9C to 40.0C
>40.0C
8.2.2. Clinical Safety Laboratory Assessments – Maternal and Infant Participants
There are no protocol-required laboratory assessments.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 2.
AEs will be reported by the maternal participant/parent(s)/legal guardian(s).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
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and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or caused the participant to discontinue from 
the study (see Section 7). 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
Maternal Participants
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each maternal participant including her fetus begins from the time the maternal 
participant provides informed consent, which is obtained before participation in the study 
(ie, before undergoing any study-related procedure and/or receiving investigational product), 
through and including a minimum of 28 calendar days after the last administration of the 
investigational product.
In this study, the investigator and site staff will ensure the active elicitation and collection of 
safety events as detailed below:

The active collection period for nonserious AEs begins once informed consent has been 
provided and continues through a minimum of 28 calendar days after vaccination.  

The active collection period for SAEs begins once informed consent has been provided 
until the maternal participant completes the study.

In addition, AEs occurring up to 48 hours after blood draws that are related to study 
procedures must be reported in the CRF.  

Details of any MA-RTI will not be collected as AEs/SAEs from informed consent until 
the maternal participant completes the study, unless the investigator or an appropriate 
designee deems the event to be possibly related to the investigational product. 
For maternal participants who are screen failures, the active collection period ends when 
screen failure status is determined.
Infant Participants
For the infant participant, the time period for actively eliciting and collecting safety events is 
detailed below:

The active collection period for nonserious AEs begins at birth and continues through and 
including a minimum of 28 calendar days after birth. 

The active collection period for NDCMCs and SAEs begins at birth and continues 
through the last study visit.  
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o
Details of any MA-RTI will not be collected as AEs/SAEs from informed consent 
until the infant participant completes the study, unless the investigator or an 
appropriate designee deems the event to be possibly related to the 
investigational product. See Section 8.1 for the reporting procedures for 
efficacy-related endpoints. Note: Details of the MA-RTI visit should be recorded 
in the eCRF.

In addition, AEs occurring up to 48 hours after blood draws or nasal swabs that are 
related to study procedures must be reported in the CRF.  
For maternal participants, and parent(s)/legal guardian(s) of infant participants born to 
maternal participants, who withdraw from the study and withdraw consent for the collection 
of future information, the active collection period ends when consent is withdrawn. 
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form and the Exposure During Pregnancy Supplemental Form 
if applicable.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy;
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those that occur within 1 month after birth; or congenital anomaly 
[in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.  In addition, infant deaths after 
1 month of age should be reported as SAEs. 
Further follow-up may be requested by the sponsor and will be handled on a case-by-case 
basis (eg, follow-up on preterm infants to identify developmental delays). 
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety. 
The same is applied for those SAEs after the active collection period has ended, should they 
occur to the fetus.  In addition, infant deaths that occur after 12 months of age should be 
reported as SAEs when the investigator believes the death has at least a reasonable possibility 
of being related to investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
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8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All AEs/SAEs occurring in a participant during the active collection period are recorded in 
the CRF.
The investigator obtains general information on the pregnancy and its outcome for all study 
participants.  The investigator will follow the pregnancy until completion (or until pregnancy 
termination).  In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth.  In the event of a termination, the reason(s) for termination should be 
specified and, if clinically possible, the structural integrity of the terminated fetus should be 
assessed by gross visual inspection (unless preprocedure test findings are conclusive for a 
congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy;
spontaneous abortion, including miscarriage and missed abortion; intrauterine fetal demise;
neonatal death, defined as those deaths that occur within 1 month after birth; or congenital 
anomaly [in a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal 
death]), the investigator should record this information in the CRF.  In addition, infant deaths 
after 1 month of age should be recorded in the CRF as SAEs. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.4).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 2.
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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/EC, if appropriate according to local 
requirements.
Potential efficacy endpoints on this study as defined in Section 8.1 will be excluded from the 
standard SAE reporting process unless deemed possibly related to investigational product.  
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the 
Investigational Product
8.3.5.1. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure-during-breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.3.5.2. Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
investigational product, which may or may not lead to the occurrence of an AE. 
In addition, the scenarios below describe environmental exposures that could lead to an 
exposure during pregnancy (EDP): 
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
A female becomes or is found to be pregnant, having been exposed (eg, because of 
environmental exposure) to the investigational product; or the female becomes or is 
found to be pregnant after being exposed to the investigational product;

A male has been exposed (eg, because of environmental exposure) to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy. 
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form and the Exposure During Pregnancy 
Supplemental form, as applicable, regardless of whether there is an associated SAE.  In the 
event of an EDP, the information submitted should include the anticipated date of delivery.  
Since the information does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed CT SAE Report Form is 
maintained in the ISF.
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
are as follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.
8.3.6. Medical Device Incidents (Including Malfunctions)
Medical devices are being provided for use in this study for the purposes of administering the 
investigational product.  In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of incident or malfunction that occur during the study with such devices.
The definition of a medical device incident can be found in Appendix 4.
NOTE: Incidents fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 2 of the protocol.
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8.3.6.1. Time Period for Detecting Medical Device Incidents
Medical device incidents or malfunctions of the device that result in an incident will be 
detected, documented, and reported during all periods of the study in which the medical 
device is used.
If the investigator learns of any incident at any time after a participant has been discharged 
from the study, and such incident is considered reasonably related to a medical device 
provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device incidents is provided in Appendix 4.
8.3.6.2. Follow-up of Medical Device Incidents
All medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs (see Section 8.3.3).  This applies to all participants, including those who 
discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the incident.
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator.
8.3.6.3. Prompt Reporting of Medical Device Incidents to Sponsor
Medical device incidents will be reported to the sponsor within 24 hours after the investigator 
determines that the event meets the protocol definition of a medical device incident.
Refer to the IP manual for instructions on reporting medical device incidents. 
The same individual will be the contact for the receipt of medical device reports and SAEs.
8.3.6.4. Regulatory Reporting Requirements for Medical Device Incidents
The investigator will promptly report all incidents occurring with any medical device 
provided for use in the study in order for the sponsor to fulfill the legal responsibility to 
notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of incidents to the IRB/EC.
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8.3.7. Medication Errors 
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.  
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration by an incorrect route;

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
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8.4. Treatment of Overdose
For this study, any dose of investigational product greater than 0.5 mL will be considered an 
overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose in the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
No interruptions or dose modifications will be made in this study. 
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Health Economics
Health economics will be evaluated in exploratory analyses assessing vaccine impact on 
healthcare resource utilization parameters evaluated during study visits, which may include 
the following: number and type of medical visits, length of hospital stay, requirement for 
mechanical ventilation, requirement for respiratory diagnostic procedures, requirement for IV 
fluids, requirement for prescriptions, and antibiotic use. 
8.10. Procedures – Maternal Participants 
8.10.1. Screening and Vaccination Visit (Clinic; Day -28 to Day 1 – Visit 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant. Each signature on the 
ICD must be personally dated by the signatory.  
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Maternal participants who might be illiterate must thumbprint the ICD and it must be signed 
and dated by an impartial witness who was present throughout the entire informed consent 
process before performing any study-related procedures.
The investigator or his or her designee will also sign and date the ICD.  A copy of the 
signed/thumbprinted and dated ICD must be given to the maternal participant.  The source 
data must reflect that the informed consent was obtained before participation in the 
study.
If the maternal participant is found ineligible for the study based on a full assessment of 
inclusion and exclusion criteria, the investigator may advise the participant, either by 
telephone or face to face, that the participant will be excluded from further participation in 
the study, as defined in Section 5.4.  All eligible maternal participants will proceed to 
complete the vaccination visit.
Standard-of-care procedures performed prior to informed consent can be considered for use 
in the study provided they are performed in close proximity (approximately 28 days) to the 
timing of vaccination and follow guidance around the timing of procedures stipulated in the 
protocol.
In countries/locales where procedures to confirm maternal participant eligibility for
this clinical trial are not routinely performed, the procedures must be obtained and 
reviewed by the investigator or qualified designee 28 days prior to vaccination.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.
The following procedures will be performed:

Obtain written informed consent from the maternal participant before performing any 
study-specific procedures. If the maternal participant is illiterate, she must thumbprint 
the ICD and it must be signed and dated by an impartial witness who was present 
throughout the entire informed consent process.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, and ethnicity).  The date of birth will be collected to 
critically evaluate the immune response and safety profile by age.

Obtain and record current alcohol, tobacco, marijuana, or any illicit drug usage.

Obtain and record any medical, surgical, and obstetric history of clinical significance 
including history from prior and current pregnancy(ies).  Refer to the ISF for further 
details.
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
Record the LMP and estimated delivery date (EDD).

Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.

Record in the source documentation the weight and height at first obstetric visit during 
current pregnancy and date of measurements.

Perform targeted physical examination evaluating/noting any clinically significant 
abnormalities within the following body systems: general appearance; skin; head, eyes, 
ears, nose, and throat; heart; lungs; abdomen; musculoskeletal; extremities; neurological; 
and lymph nodes.  Significant medical and surgical history and abnormal observations 
from the physical examination will be documented and recorded in the CRF. 

Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement.
o
Where an obstetric ultrasound examination is not performed at 18 weeks of 
pregnancy as part of prenatal standard of care, perform an ultrasound examination.
o
Note: Physical or obstetric examinations performed as standard of care may be 
admissible if performed within 10 days prior to the vaccination visit.

Obtain details of any Ig (including monoclonal antibodies or immune globulin [Rho(D) 
immune globulin, eg, RhoGAM]) or blood products (eg, whole blood, packed cells) given 
at any time during the current pregnancy.

Obtain details of any nonstudy vaccinations given at any time during the current 
pregnancy.

Obtain details of syphilis, HIV, and HBV status.  

Note: Only participants with a documented negative syphilis test result and negative 
HIV antibody and HBV surface antigen test results obtained during the current 
pregnancy are eligible for randomization. 

If not performed as standard of care, assessment should be performed as part of the 
study, locally, and vaccination of maternal participant should be deferred until the 
results are available and confirmed to be negative within 28 days prior to study 
randomization. 

Ensure and document that all the inclusion criteria and none of the exclusion 
criteria are met.

Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.2.3.
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
Issue the maternal participant an e-diary and provide instructions on its completion.

Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures, and provide instructions on their use.

Obtain and record baseline assessment of systemic events prior to vaccination in the 
maternal participant’s source documents. Ask the maternal participant to capture the 
corresponding baseline systemic event measurements in her e-diary.

Prior to vaccination, collect a blood sample of approximately 15 mL for serologic 
assessments.

Obtain the maternal participant’s randomization number and investigational product kit 
number using the IRT system. Refer to the IRT manual for further instructions on this 
process.  

Qualified site staff member(s) will administer a single 0.5-mL dose of investigational 
product into the deltoid muscle of the (preferably) nondominant arm, unless medically 
contraindicated, in which case the injection may be administered in the dominant arm. 
Please refer to the IP manual for further instruction on this procedure.

Site staff must observe the maternal participant for any acute reactions for at least 
30 minutes after investigational product administration.  

Record any acute reactions in the maternal participant’s source documents, on the AE 
page of the CRF, and on an SAE form as applicable.

Ask the maternal participant to complete the e-diary from Day 1 to Day 7, with Day 1 
being the day of vaccination, OR explain to the maternal participant that a field worker 
will visit her every day from Day 2 to Day 7 after vaccination (where Day 1 is the day of 
vaccination) to take her temperature and record systemic events, acute local reactions, 
and use of antipyretic medication in a diary (if applicable).

Ask the maternal participant to contact the site staff or investigator immediately if she 
experiences any of the following from Day 1 to Day 7 after vaccination to determine if an 
unscheduled reactogenicity visit is required as detailed in Section 8.10.5 OR inform the 
maternal participant that if she experiences any of the following from Day 1 to Day 7 
after vaccination or is taking antipyretic medication at Day 7, then the field worker will 
continue to visit until resolution.  Furthermore, the maternal participant will be referred to 
the appropriate healthcare facility at the discretion of a field worker if there are any 
concerns as detailed in Section 8.10.5.

Fever 39.0C (102.1F).

Redness or swelling at the injection site measuring >20 measuring device units 
(greater than 10 cm).
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
Severe pain at the injection site.

Any severe systemic event.

Any blackening of the skin (necrosis) at the injection site.

Any peeling/scaling of the skin (exfoliative dermatitis). 

Inform the maternal participants that if a temperature of 100.4F (38.0°C) is recorded 
during the collection of diary data, she will be required to have a rapid test for malaria as 
per local practice and details will be recorded in the diary (if applicable, based on local 
practice).

Remind maternal participants that study staff may contact them to obtain additional 
information on events entered into the e-diary.

Remind maternal participants to inform the study staff of any AEs and SAEs that occur 
for the duration of the trial as described in Section 8.2 and Section 10.2.

Remind the maternal participant to bring the completed e-diary to the next visit
(if applicable). 

Complete the source documents.

The investigator or an authorized designee completes the CRFs and the blinded 
dispenser/administrator completes the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate participant compliance and as part of the ongoing 
safety review.  

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6. 

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit (The field worker will contact the maternal participant prior to the next 
study visit to remind her, if applicable).
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8.10.2. 1-Month Follow-up Visit (Clinic or Telephone; 28 to 42 Days After Vaccination) 
If delivery occurs before this visit, this visit will not be conducted.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.

Review the participant’s e-diary data. Collect stop dates of any e-diary events ongoing 
on the last day that the e-diary was completed and record stop dates in the CRF.

Record details of any MA-RTI, including if the MA-RTI is infectious or noninfectious, 
location details (upper or lower RTI), and prescribed medications since the last visit. 

Record details of any nonstudy vaccinations given since the last visit.

Complete the maternal participant’s source documents.

Record AEs and SAEs as described in Section 8.2 and Section 10.2. Note: Active 
elicitation and collection of AEs and SAEs through 28 days after vaccination must occur 
even if delivery occurs within 28 days after vaccination.

The investigator or an authorized designee completes the CRF.

Maternal participants will be instructed to contact the site to report any significant illness 
(new or worsening), any medically attended respiratory events (eg, doctor’s visit, 
emergency room visit), or any hospitalization that occurs during the study period as 
detailed in Section 8.10.6. 

Request the maternal participant to contact the site if she goes into labor/is admitted to 
the maternal unit (The field worker will contact the maternal participant prior to the next 
study visit to remind her, if applicable).
8.10.3. Delivery (Maternity Unit)
The delivery visit spans the time from when a participant is admitted in labor through 
discharge following delivery of her infant. Protocol-specified procedures associated with 
this delivery visit may be done at any time during this period.

Ensure that the maternal participant continues to be eligible for the study and meets none 
of the participant withdrawal criteria as described in Section 7.2.

Obtain details of any antenatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [Rho(D) immune globulin, eg, RhoGAM]) or blood products (eg, whole 
blood, packed cells) given since the last visit.
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
If available, record the maternal participant’s GBS status and if any medication was given 
for IAP.

Record details of any nonstudy vaccinations given since the last visit.

Collect a blood sample of approximately 15 mL for serologic assessments.  Note:  The 
maternal participant’s blood sample can be taken at any time during the delivery visit, 
preferably before delivery. In the event that the blood sample cannot be obtained before 
delivery, the sample should be collected as close to delivery as possible and at most 
48 hours postpartum. Refer to the ISF for blood sample collection guidelines.
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments 
must also be collected.  Cord blood is collected from the umbilical cord vein attached to 
the placenta prior to the blood clotting within the cord and after the umbilical cord has 
been clamped and cut.  This sample should be labeled with the infant’s participant ID 
number.

Record pregnancy outcome information including vital status of the infant (live, stillbirth, 
spontaneous abortion, or miscarriage), mode of delivery (vaginal delivery, cesarean 
section, etc), and the use of any assisted devices (forceps or vacuum).  

Record details of any MA-RTI associated with a medical visit, including if the MA-RTI 
is infectious or noninfectious, location details (upper or lower RTI), and prescribed 
medications since the last visit. 

Record AEs as described in Section 8.2 and Section 10.2.

Ask the maternal participants to contact the site to report any significant illness (new or 
worsening), any medically attended respiratory events (eg, doctor’s visit, emergency 
room visit), or any hospitalization that occurs during the study period as detailed in 
Section 8.10.6.

Ask the maternal participant to contact the site staff or investigator if her newborn infant 
meets the MA-RTI assessment criteria OR the field worker will contact the maternal 
participant/legal guardian(s) weekly to remind them to report any MA-RTI (if 
applicable).

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
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8.10.4. 6-Month-Postdelivery Visit (Clinic or Telephone; 180 to 210 Days After 
Delivery)

Obtain details of any postnatal steroid treatment, Ig (including monoclonal antibodies or 
immune globulin [eg, HBIG]) or Rho(D) immune globulin [eg, RhoGAM]) or blood 
products (eg, whole blood, packed cells) given since the last visit.

Record details of any nonstudy vaccinations given since the last visit.

Record details of any MA-RTI, including if the MA-RTI is infectious or noninfectious, 
location details (upper or lower RTI), and prescribed medications since the last visit.

Ask the maternal participant to contact the site staff or investigator if her infant meets the 
MA-RTI assessment criteria OR the field worker will contact the maternal 
participant/legal guardian(s) weekly to remind them to report any MA-RTI, if applicable.

Record AEs as described in Section 8.2 and Section 10.2.

Complete the maternal participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.10.5. Unscheduled Reactogenicity Visits 
If the maternal participant reports 1 or more of the following, a contact must occur as soon as 
possible between the maternal participant and the investigator, or a medically qualified 
member of the study site staff, to assess if an unscheduled reactogenicity visit is required OR
based on local practice in certain countries/locales, maternal participants will be referred to 
the appropriate healthcare facility at the discretion of the field worker if there are any 
concerns regarding reactogenicity events, including:

redness at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

swelling at the injection site on the arm in which the investigational product was 
administered measuring >20 measuring device units (>10.0 cm),

severe injection site pain on the arm that the investigational product was 
administered, 

fever 39.0C (102.1F).
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The maternal participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or
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
The participant/field worker recorded an incorrect value in the e-diary (confirmation 
of an e-diary data entry error), or

The investigator or appropriate designee determines that the visit is not required.
This contact will be recorded in the maternal participant’s source notes and in the CRF.
Any ongoing reactions must be assessed at the next scheduled visit.
The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure oral temperature.

Measure the participant’s heart rate.

Measure the participant’s blood pressure (seated).

Measure the minimum and maximum diameters of redness (if present) on the arm in 
which the investigational product was administered.

Measure the minimum and maximum diameters of swelling (if present) on the arm in 
which the investigational product was administered.

Assess if necrosis is present at the injection site on the arm in which the investigational 
product was administered.

Assess if any exfoliative dermatitis is present.

Assess any injection site pain on the arm in which the investigational product was 
administered that is present in accordance with the reactogenicity grading scale provided 
in Section 8.2.1.1.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 8.2.1.2.

Ask the participant if she attended an emergency room visit or was hospitalized.

For severe pain at the injection site resulting in an emergency room visit or 
hospitalization, severe systemic events associated with an emergency room visit or 
hospitalization, any necrosis on the arm in which the investigational product was 
administered, or exfoliative dermatitis, the investigator or qualified designee must assess 
these events in accordance with the intensity AE grading scale provided in
Section 8.2.1.1 and Section 8.2.1.2.
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
Record AEs and SAEs as described in Section 8.2 and Section 10.2.

Complete the participant’s source documents.

The investigator or an authorized designee will complete the CRFs.
The study staff/field worker may contact the participant to obtain additional information on 
events entered into the e-diary, as appropriate.
8.10.6. RTI Surveillance Procedures and Telephone Contact Criteria – Maternal 
Participants

Starting from Day 1 after vaccination (where Day 1 is the day of vaccination) until the 
end of the study, all maternal participants will be monitored for MA-RTIs as detailed in 
Section 1.2.3.1 and Section 8.1.2. Maternal participants should notify the site and/field 
worker of the occurrence of any MA-RTIs immediately but no later than the next study 
visit. Note: Site contact may be by an electronic method of communication (including 
but not limited to electronic messaging, short message service [SMS], text, email), by 
phone call, or by face-to-face contact.

The definition of maternal RTI includes 1 or more of the following signs and/or 
symptoms:
o
New or increased sore throat
o
New or increased cough
o
New or increased nasal congestion
o
New or increased nasal discharge
o
New or increased wheezing
o
New or increased sputum production
o
New or increased shortness of breath

Record the details of any MA-RTI, including the medically attended visit location 
(hospital, outpatient visit, emergency room, urgent care, or home visit), duration of 
hospitalization, intensive care unit (ICU) duration if applicable, prescribed medications 
for the MA-RTI, assessments including RSV test result (eg, NAAT, rapid antigen 
detection tests, or any other molecular diagnostic test), if available, and the final 
diagnosis.

Based on the diagnosis provided, the investigator should denote whether the medically 
attended respiratory illness was infectious or noninfectious, and comprised the upper 
and/or lower airways. 
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
Record the details of any nonstudy vaccinations.

Record AEs as described in Section 8.2 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Complete the participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11. Procedures – Infant Participants
8.11.1. Infant Participants: Visit 1 – Birth (Hospital, Birth to 7 Days After Birth)

Manually assign a single infant participant identifier using the IRT system (or 
equivalent).

Collect a cord blood sample of approximately 10 mL for immunogenicity assessments.  
Cord blood is collected from the umbilical cord vein attached to the placenta prior to the 
blood clotting within the cord and after the umbilical cord has been clamped and cut.  
This sample should be labeled with the infant’s participant ID number.

If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 24 hours, but up to 7 days after birth.  The volume of blood collected 
will be based on the weight of the infant (refer to Table 4).

Ensure and document that all the infant inclusion criteria and none of the infant exclusion 
criteria are met.

Collect demography (including complete date of birth [ie, dd-Mmm-YYYY], sex, race, 
and ethnicity).  The date of birth will be collected to critically evaluate the immune 
response.

Obtain and record the infant’s length, head circumference, and weight at birth.
Note: Birth weight must be the first birth weight and cannot be based on the 
standard-of-care examination.

Obtain and record the infant’s birth data, including GA and appearance, pulse, 
grimace, activity, and respiration (Apgar) score. 

Obtain and record background factors as described in Section 10.5.

Measure vital signs, including rectal temperature, heart rate, oxygen saturation by 
pulse oximetry, and respiratory rate.

Standard-of-care physical examination procedures can be considered for use in the 
study provided they were performed within 48 hours after birth. Note: Please 
reference the physical examination procedures below for details. 
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
Perform a physical examination, if not performed as part of standard of care, noting 
any clinically significant abnormalities within the following body systems: general 
appearance; skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; back; 
musculoskeletal; extremities; genitourinary; neurological; and lymph nodes.  
Abnormal results must be recorded on source documents as well as the physical 
examination pages of the CRF; only if the abnormal finding is deemed to be clinically 
significant should this be recorded on the AE pages of the CRF. 

Record details of any major congenital anomalies on the AE page of the CRF, and 
report as an SAE as described in Section 10.2.3.

Record any medication as described in Section 6.5.5.

Obtain details of any Ig (including monoclonal antibodies [eg, Synagis] or immune 
globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given to the 
infant participant since birth.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Review the weekly contact schedule with the parent(s)/legal guardian(s) and collect 
contact information OR remind the parent(s)/legal guardian(s) that a field worker will 
contact them weekly to remind them to report any MA-RTI (if applicable).

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI visit criteria. An MA-RTI assessment visit along with collection of a nasal swab 
must be performed for all MA-RTIs as described in Section 1.2.4.1 and Section 8.11.7.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.
8.11.2. Visit 2 – 1-Month Follow-up (Clinic, 28 to 48 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 

Measure vital signs, including temperature, heart rate, oxygen saturation by pulse 
oximetry, and respiratory rate.

Standard-of-care physical examination procedures can be considered for use at this study 
visit, if they were performed 14 days prior to this visit. Note: Please reference the 
physical examination procedures below for reporting details. 
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
Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities. Newly identified abnormal findings must 
be recorded on source documents and the physical examination page and, if considered 
clinically significant in the judgment of the investigator/examiner, on the AE page of the 
CRF.

Record details of any newly emergent major congenital anomalies on the AE page of 
the CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Ask the parent(s)/legal guardian(s) to contact the investigator or qualified designee 
immediately if any significant illness or hospitalization occurs or if the infant meets the 
MA-RTI assessment criteria.  An MA-RTI assessment visit along with collection of a 
nasal swab must be performed for all MA-RTIs as described in Section 1.2.4.1 and 
Section 8.11.7.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every 7 days 
from birth until the 6-month follow-up visit to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the RTI medical visit criteria.  
The weekly contact may be a text, email, phone call, or face-to-face contact with the site 
staff/field worker. Please refer to Section 8.11.7.1 for guidance on reported cases of MA-
RTIs in infant participants during the first 6 months after birth. 
8.11.3. Visit 3 – 6-Month Follow-up Visit (Clinic, 180 to 210 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight. 

Standard-of-care physical examination procedures can be considered for use at this study 
visit, if they were performed 14 days prior to this visit. Note: Please reference the 
physical examination procedures below for reporting details. 
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Page 84

Perform a targeted physical examination, if not performed as part of standard of care, 
noting any clinically significant abnormalities. Newly identified abnormal findings must 
be recorded on source documents and the physical examination page and, if considered 
clinically significant in the judgment of the investigator/examiner, on the AE page of the 
CRF.

Record details of any newly emergent major congenital anomalies on the AE page of 
the CRF, and report as an SAE as described in Section 10.2.3.

Record details of any NDCMCs. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI assessment
criteria.  The monthly contact may be a text, email, phone call, or face-to-face contact
with the site staff/field worker. Please refer to Section 8.11.8 for guidance on reported 
cases of MA-RTIs in infant participants. 

Ask the parent(s)/legal guardian(s) to contact the investigator immediately if any 
significant illness or hospitalization occurs or if the infant meets the MA-RTI assessment
criteria.  An MA-RTI assessment visit along with a nasal swab must be performed 
for all hospitalizations due to an RTI and severe MA-LRTIs as described in 
Section 1.2.4.1 and Section 8.11.8.
8.11.4. Visit 4 – 12-Month Follow-up (Clinic or Telephone; 350 to 378 Days After Birth)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if
a clinic visit is conducted). 

Standard-of-care physical examination procedures can be considered for use at this study 
visit, if they were performed 14 days prior to this visit. Note: Please reference the 
physical examination procedures below for details.
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Page 85

Perform a targeted physical examination, if not performed as part of routine care as 
described above, noting any clinically significant abnormalities. Newly identified 
abnormal findings must be recorded on source documents and the physical examination 
page and, if considered clinically significant in the judgment of the 
investigator/examiner, on the AE page of the CRF. Only applicable if a clinic visit is 
conducted.

Obtain and record details of any NDCMCs or newly emergent major congenital 
anomalies. 

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants except for infant participants born during the first year of the study.

The investigator or an authorized designee completes the CRF for infant participants born 
during the first year of the study. Note: An additional 12-month blinded follow-up period 
for longer-term RTI surveillance and safety oversight will be included for these 
participants.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Confirm the understanding of the infant participant’s parent(s)/legal guardian(s) 
regarding site contact for the study, which is approximately every month (28 to 35 days) 
until the end-of-study visit. Ask the parent(s)/legal guardian(s) to contact the 
investigational site/field worker promptly if the infant meets the MA-RTI assessment
criteria.  The monthly contact may be a text, email, phone call, or face-to-face contact
with the site staff/field worker. Please refer to Section 8.11.8 for guidance on reported 
cases of MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI assessment criteria.  
An MA-RTI visit along with collection of a nasal swab must be performed for all 
hospitalizations due to an RTI and severe MA-LRTIs as described in Section 1.2.4.1
and Section 8.11.8.
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8.11.5. Visit 5 – 18-Month Follow-up Visit (Telephone; 525 to 574 Days After Birth; 
Infant Participants Born During the First Year of the Study Only)

Obtain and record background factors as described in Section 10.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Obtain and record details of any NDCMCs or newly emergent major congenital 
anomalies.

Record AEs as described in Section 8.3 and Section 10.2.

Ensure the parent(s)/legal guardian(s) is comfortable with the chosen communication 
technology as described in Section 8.12.

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF.

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) until the end-of-study visit, to remind the parent(s)/legal guardian(s) to 
contact the investigational site promptly if the infant meets the MA-RTI assessment
criteria.  The monthly contact may be a text, email, phone call, or face-to-face contact
with the site staff/field worker. Please refer to Section 8.11.8 for guidance on reported 
cases of MA-RTIs in infant participants. 

Infant participants born during the first year of the study only: Ask the parent(s)/legal 
guardian(s) to contact the investigator immediately if any significant illness or 
hospitalization occurs or if the infant meets the MA-RTI assessment criteria.  
An MA-RTI assessment visit along with collection of a nasal swab must be 
performed for all hospitalizations due to an RTI and severe MA-LRTIs as described 
in Section 1.2.4.1 and Section 8.11.8.
8.11.6. Visit 6 – 24-Month Follow-up Visit (Clinic or Telephone; 714 to 742 Days After 
Birth; Infant Participants Born During the First Year of the Study)

Obtain and record background factors as described in Section 10.5.

Obtain and record the infant’s length, head circumference, and weight (only applicable if 
a clinic visit is conducted). 

Standard-of-care physical examination procedures can be considered for use at this study 
visit, if they were performed 14 days prior to this visit. Note: Please reference the 
physical examination procedures below for reporting details. 
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
Perform a targeted physical examination, if not performed as part of routine care, noting 
any clinically significant abnormalities. Newly identified abnormal findings must be 
recorded on source documents and the physical examination page and, if considered 
clinically significant in the judgment of the investigator/examiner, on the AE page of the 
CRF. Only applicable if a clinic visit is conducted.

Obtain and record details of any NDCMCs or newly emergent major congenital 
anomalies.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.

Complete the infant participant’s source documents. 

The investigator or an authorized designee completes the end-of-study CRF for all infant 
participants born during the first year of the study.
8.11.7. Active RSV Surveillance Procedures and Visit Criteria (Birth to 6 Months After 
Delivery)

This is an active surveillance period spanning from birth through 6 months after delivery 
(Visit 3).

The sponsor may alter the frequency of the weekly contacts or the duration of 
surveillance for MA-RTI based on RSV surveillance data or other operational factors.
8.11.7.1. RTI Associated With a Medical Visit – Hospital, Home, or Clinic Visit

Contact the infant participant’s parent(s)/legal guardian(s) approximately every week 
(7 to 10 days) from birth until Visit 3 (6-month follow-up visit), to remind the 
parent(s)/legal guardian(s) to contact the investigational site promptly if the infant meets 
the criteria for an RTI-associated medical visit.  The weekly contact may be via the e-
diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Table 1 regarding clinical signs 
and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an event requiring a visit to a healthcare provider, the site staff 
and/field worker should confirm, based on information provided, whether the event meets 
the criteria for an MA-RTI. Please refer to Table 1 and  Section 8.1 regarding clinical 
signs and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.
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
When an infant MA-RTI criterion is met or confirmed, the site/field worker will obtain 
records from the medically attended visit and record the healthcare information as 
detailed in Appendix 6.

When an infant MA-RTI criterion is met or confirmed, the infant participant will be 
seen as soon as possible and within 72 hours of site/field worker awareness for 
assessment by the investigational site staff or qualified designee. 

The infant participant may be seen either at the time of the MA-RTI, at home or at the 
study site (if discharged), or if the infant participant has been hospitalized or is receiving 
treatment at another medical facility, the site staff/field worker can conduct the visit at 
those facilities.  
o
If a study visit is not performed within 72 hours of site/field worker awareness, it 
should still be performed, including the collection of nasal swab specimens. 
o
Targeted assessments at an MA-RTI assessment visit include but are not limited to:
o
Respiratory signs: apnea (observed only) or lower chest wall indrawing.
o
Vital sign assessment: respiratory rate, heart rate, and oxygen saturation by pulse 
oximetry.

Nasal swab collection from the infant participant for testing at the central laboratory.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the RTI event, including office visits, urgent care, and 
emergency room or hospitalization details, including the date and time of the visit.  
Record the following in the CRF based on the site records:
o
Respiratory signs: apnea (noted to be observed only) or lower chest wall indrawing.
o
Vital sign assessment: respiratory rate, heart rate, and oxygen saturation by pulse 
oximetry.
o
Note: record the values that represent the worst day of illness.

Record any medication as described in Section 6.5.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2. Note: MA-RTIs are study 
endpoints and should not be reported as AEs.
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
Request that the parent(s)/legal guardian(s) contact the site/field worker if the infant’s 
illness worsens, or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for the event as detailed in Section 8.1.
8.11.8. Long-Term RSV and Safety Surveillance Procedures and Visit Criteria

This is a long-term surveillance procedure for all infant participants from 6 months after 
delivery (Visit 3) until the last study visit.  

Contact the infant participant’s parent(s)/legal guardian(s) approximately every month 
(28 to 35 days) from Visit 3 (6-month follow-up visit) until the end-of-study visit, to 
remind the parent(s)/legal guardian(s) to contact the investigational site promptly if the 
infant meets the criteria for an MA-RTI visit.  The monthly contact may be via the e-
diary device or study-related mobile application, text, email, phone call, or face-to-face 
contact with the site staff/field worker. Please refer to Section 8.1 regarding clinical signs 
and symptoms that meet the study definition of an MA-RTI, and Section 1.2.4.1 for 
study-required assessments.

Note: If the parent(s)/legal guardian(s) reports to the investigational site staff that the 
infant has experienced an MA-RTI, the site should obtain additional information and 
determine whether the event also meets the study definition of a severe MA-LRTI. 
o
Note: Severe MA-LRTI is defined in Table 1.

The site/field worker will obtain records from the medically attended visit and record the 
healthcare information as detailed in Appendix 6.

When an infant MA-RTI criterion is confirmed and also meets the study definition of 
hospitalization due to an RTI or a severe MA-LRTI, the infant participant will be seen 
as soon as possible and within 72 hours of site/field worker awareness for nasal swab 
collection by the investigational site staff/field worker. The staff/field worker will obtain 
the nasal swab within 72 hours of awareness with the infant participant either at home 
(if discharged) or, if the infant participant has been hospitalized or receiving treatment at 
another medical facility, the site staff/field worker will conduct the visit at those 
facilities.  
o
Note: Nasal swab collection from the infant participant is for testing at the central 
laboratory.

Targeted assessments will be required for all reported cases of hospitalization due to an 
RTI or severe MA-LRTI only, and this includes but is not limited to:
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o
Respiratory signs: apnea, lower chest wall indrawing.
o
Vital sign assessment: respiratory rate, heart rate, and oxygen saturation by pulse 
oximetry.

A targeted assessment visit is not required for an MA-RTI event not meeting the 
definition of hospitalization due to an RTI or severe MA-LRTI.

Obtain and record background factors as described in Section 10.5.

Obtain and record details of the MA-RTI event, including emergency room or 
hospitalization details with admission and discharge date (if applicable).

Record any medication as described in Section 6.5.5.

Obtain and record details of any Ig (including monoclonal antibodies [eg, Synagis] or 
immune globulin [eg, HBIG]) or blood products (eg, whole blood, packed cells) given 
since the last visit.

Record AEs as described in Section 8.3 and Section 10.2.  Note: MA-RTIs are study 
endpoints and should not be reported as AEs.

Request that the parent(s)/legal guardian(s) contact the site if the infant’s illness worsens, 
or if the infant is hospitalized. 

Complete the infant participant’s source documents.

The investigator or an authorized designee completes the CRF. 

Compile the adjudication submission package for hospitalizations due to an RTI and 
severe MA-LRTI events only as detailed in Section 8.1.
8.12. Communication and Use of Technology
In a study of this duration that is event-driven, it is vital to ensure that communication 
between the study site and the maternal participant and parent(s)/legal guardian(s) is 
maintained to ensure that endpoint events are not missed.  This study will employ various 
methods, tailored to the individual participant (maternal and/or infant participant), to ensure 
that communication is maintained and study information can be transmitted securely.  Using 
appropriate technology, a communication pathway between the maternal participant and 
parent(s)/legal guardian(s) and the study site staff will be established.  The maternal 
participant and the parent(s)/legal guardian(s) may be able to utilize their own devices to 
access this technology, or use a device provided by the sponsor.  Traditional methods of 
telephone communication will also be available. The technology solution may facilitate the 
following:
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
Contact with the investigator.

The ability of the maternal participant/parent(s)/legal guardian(s) to report MA-RTI visits
associated with the infant participant.

An alert in the event that the maternal or infant participant is hospitalized.

Visit reminders.

Messages of thanks and encouragement from the study team.

A platform for recording local reactions and systemic events (e-diary).
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Estimands and Statistical Hypotheses
The null hypothesis to be tested concerns VE for the primary endpoint. The RSV vaccine 
will be compared to placebo, testing the hypotheses H0: VE 20% vs Ha: VE >20%. For all 
secondary efficacy endpoints, the RSV vaccine will be compared to placebo, testing the 
hypotheses H0: VE 0% vs Ha: VE >0%. Hypothesis testing of the secondary endpoints is 
conditional upon rejection of the null hypothesis for at least 1 of the primary endpoints.
9.1.1. Estimands – Infant Participants
9.1.1.1. Efficacy
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with key protocol criteria (evaluable participants): 

VE, defined as the percentage relative risk reduction in the incidence of MA-LRTI due to 
RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of severe MA-LRTI 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of hospitalization 
due to RSV in the RSV vaccine group, relative to the placebo group;

VE, defined as the percentage relative risk reduction in the incidence of all-cause 
MA-LRTI in the RSV vaccine group, relative to the placebo group.
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These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  For participants who 
discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.2. Immunogenicity
In infant participants born to maternal participants receiving 1 dose of investigational product 
and in compliance with the key protocol criteria (evaluable participants):

Functional antibody levels estimated by the GMT for RSV A– and RSV B–neutralizing 
antibody titers.

Geometric mean ratio (GMR), estimated by the ratio of the GMTs for RSV A– and 
RSV B–neutralizing antibody titers of the RSV vaccine group to the placebo group.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as missing completely at random (MCAR) is assumed.  For participants 
who discontinue from the study or have major protocol violations, all postdiscontinuation or 
postviolation observations will be censored.
9.1.1.3. Safety
In infant participants born to the maternal participants receiving 1 dose of investigational 
product:

The percentage of infant participants with specific birth outcomes.  

The percentage of infant participants having AEs from birth through 1 month of age.

The percentage of infant participants having SAEs, NDCMCs, and new diagnosed 
congenital anomalies from birth through the last study visit.
Missing AE dates and missing AE intensity will be handled according to Pfizer safety rules.
9.1.2. Estimands – Maternal Participants
9.1.2.1. Immunogenicity
In maternal participants receiving 1 dose of investigational product and in compliance with 
the key protocol criteria (evaluable participants):

The immune response, estimated by the GMT for RSV A and RSV B 50% neutralizing 
antibody titers.

The immune response, estimated by the GMFR from baseline in RSV A and RSV B 50% 
neutralizing antibody titers.
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
GMR, estimated by the ratio of the GMTs for RSV A and RSV B 50% neutralizing 
antibody titers of the RSV vaccine group to the placebo group.

Geometric mean of the IgG levels against RSV prefusion F.

Geometric mean of the Ig levels to nonvaccine RSV antigens.
These estimands estimate the vaccine effect in the hypothetical setting where participants 
follow the study schedules and protocol requirements as directed.  Missing serology results 
will not be imputed, as MCAR is assumed.  For participants who discontinue from the study 
or have major protocol violations, all postdiscontinuation or postviolation observations will 
be censored.
9.1.2.2. Safety
In maternal participants receiving 1 dose of investigational product:

The percentage of maternal participants reporting AEs through 1 month after vaccination.

The percentage of maternal participants reporting obstetric complications and SAEs 
through the end of the study.

The percentage of maternal participants reporting local reactions within 7 days of 
vaccination, in the subset of participants completing e-diaries.

The percentage of maternal participants reporting systemic events within 7 days of 
vaccination, in the subset of participants completing e-diaries.
Missing e-diary data will not be imputed; missing AE dates and missing AE intensity will be 
handled according to Pfizer safety rules.
9.2. Sample Size Determination
This is a case-driven study. Sample size is determined as the number of participants to be 
randomized that is expected to accrue the required number of primary endpoint cases in the 
evaluable population. In this study there are 2 primary endpoints, and success on either 
primary endpoint is sufficient (see Section 9.1); power for the study overall is therefore at 
least as high as the power for either primary endpoint individually. In order for the study to 
have at least 90% power to reject the null hypothesis for MA-LRTI due to RSV when true 
VE is 60%, a total of 124 cases of MA-LRTI due to RSV within 90 days of birth are required 
in the evaluable population. This also accounts for potential use of a nominal alpha of 1.25% 
1-sided within the Hochberg multiplicity adjustment. There is no explicit case target for the 
endpoint of severe MA-LRTI due to RSV; depending on the assumed true VE, power for that 
individual hypothesis may be lower, but the power for the primary endpoint family will be at 
least 90%. Hypotheses about VE may be restated as hypotheses about the proportion of 
cases in the RSV vaccine group, conditional upon a fixed total number of cases. If this 
proportion is p, the null hypothesis H0: VE 20% is equivalent to H0: p ≥0.444; the 
assumption of VE = 60% corresponds to p = 0.286. Power was evaluated by the exact 
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binomial test, and the case target established as that number k for which power is guaranteed 
to be at least 90%, for all k* ≥k. The calculation accounted for the study design 
(1:1 randomization of participants to RSV vaccine : placebo), a single planned interim 
analysis of efficacy (see Section 9.5), and an overall type 1 error of 2.5% 1-sided across the 
2 primary endpoints. 
This global study is planned to be conducted in the United States and other high-income 
countries as well as LMICs. Incidence rates of the primary endpoints are expected to vary in 
different regions. Based on a recently completed Phase 3 trial of an RSV vaccine, the 
assumed incidence rate for MA-LRTI due to RSV through 90 days in low-incidence 
countries, such as the United States, is approximately 1.75%; and in other regions,
approximately 3.90%. With these assumptions, and also allowing for 60% VE and 10% of 
enrolled participants being nonevaluable, enrollment of approximately 6900 participants is 
planned for the study as a whole. The exact number of participants required to accrue the 
case target may be higher or lower than this, depending on incidence rates, observed VE, and 
the proportion of participants evaluable.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined for infant and maternal 
participants:
Population
Description
Enrolled 
All maternal participants who sign the ICD.
Randomly assigned to 
investigational product
All maternal participants who are assigned a randomization 
number in the IRT system.
Evaluable efficacy –
infant (per-protocol)
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized at least 14 days prior to delivery, have 
valid and determinate results for the proposed analysis, and have 
no major protocol violations. 
Modified intent-to-treat 
(mITT) efficacy – infant
All infant participants who are born to vaccinated maternal 
participants and have valid and determinate results for the 
proposed analysis.
Evaluable 
immunogenicity – infant
All infant participants who are eligible, are born to the maternal 
participants who received the investigational product to which 
they were randomized, have blood drawn for assay testing 
within the specified time frame, have valid and determinate 
assay results for the proposed analysis, and have no major 
protocol violations. 
Evaluable 
immunogenicity –
maternal
All maternal participants who are eligible, receive the 
investigational product to which they were randomized, have 
blood drawn for assay testing within the specified time frame, 
have valid and determinate assay results for the proposed 
analysis, and have no major protocol violations. 
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Population
Description
mITT immunogenicity –
infant
All infant participants who are born to vaccinated maternal 
participants and have at least 1 valid and determinate assay 
result for the proposed analysis.
mITT immunogenicity –
maternal
All randomized maternal participants who receive 
investigational product and have at least 1 valid and determinate 
assay result for the proposed analysis. 
Safety – infant
All infant participants who are born to vaccinated maternal 
participants.
Safety – maternal
All randomized maternal participants who receive 
investigational product.  
9.4. Statistical Analyses 
The SAP will be developed and finalized before database lock for the first planned analysis 
and will describe the participant populations to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data.  This section is a summary of the 
planned statistical analyses of the primary, secondary, and exploratory endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The analysis of efficacy will use a conditional exact test based on the 
binomial distribution of the number of disease cases in the RSV vaccine 
group, given the total number of cases in both groups. The incidence of 
MA-LRTI due to RSV and severe MA-LRTI due to RSV in infant 
participants will be evaluated in both groups up to 90 days, 120 days, 
150 days, and 180 days after birth.

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population. 

The 2 primary endpoints of MA-LRTI due to RSV and severe MA-LRTI 
due to RSV will be tested in parallel using a Hochberg multiplicity 
adjustment procedure. Success of the trial requires rejection of the null 
hypothesis (ie, a CI lower bound >20%) for either one of the 2 primary 
endpoints.

The primary endpoint of severe MA-LRTI due to RSV may be demoted 
to a secondary endpoint, if there are insufficient cases for an adequately 
powered analysis. During the trial, blinded accrual of cases will be 
monitored and prior to any unblinding, a decision rule for this change will 
be established based on the total number of cases of severe MA-LRTI due 
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to RSV. 

Testing of each of the primary endpoints will follow a fixed sequence. 
First, the hypothesis pertaining to the incidence within 90 days after birth 
will be tested, at the full nominal alpha level. If that null hypothesis 
cannot be rejected, testing for that endpoint ends. Otherwise, testing 
proceeds to the incidence within 120 days after birth, at the full nominal 
alpha level. In the same way, testing will proceed to the endpoints 
evaluated at 150 days and 180 days, conditional on rejection of the null 
hypotheses for all earlier time intervals. 

There may be a single interim analysis of the primary endpoint when 
there is an adequate number of cases (at least half the target number 
within 90 days). Based on the fraction of cases included in the interim 
analysis, a nominal alpha level will be derived based on a Lan-DeMets
implementation of the O’Brien-Fleming alpha spending function. For 
example, if there is a single interim analysis at exactly 50% of the cases, 
the appropriate nominal 1-sided significance levels are 0.0014 at the 
interim analysis and 0.0245 at the final analysis. Implementation of these 
nominal 1-sided significance levels ensures the overall type 1 error for the 
primary endpoint will be no more than 0.025. See Section 9.5 for more 
details.

At the interim analysis there will also be an assessment for futility, based 
on conditional power for the primary endpoint. If the probability of 
success at the end of the trial is low, given the interim analysis results and 
the initially assumed VE is applied to the remaining data, consideration 
will be given to stopping the study for futility.

CIs for VE will be calculated using the nominal alpha level α. If the lower 
100(1 - α)% confidence limit for VE exceeds 20%, the null hypothesis 
will be rejected.

At the end of the trial, the RSV vaccine may be deemed efficacious if 
there are 43 or fewer cases of MA-LRTI due to RSV in the RSV vaccine 
group out of the 124 total primary endpoint cases.  This corresponds to 
estimated VE = 47% with 95.1% CI = (22%, 64%). For severe MA-LRTI, 
assuming a total of 50 cases occur, the vaccine may be deemed 
efficacious if there are 14 or fewer cases in the RSV vaccine group.  This 
corresponds to estimated VE = 61% with 95.1% CI = (26%, 81%).

Kaplan-Meier curves showing accrual of primary endpoint cases over 
180 days will be presented.
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Secondary

The analysis of secondary efficacy endpoints will use the exact 
conditional binomial method, as for the primary endpoint. Secondary 
endpoints will be examined at the final analysis only. VE will be 
estimated along with 2-sided 95% CI. 

Inference for the secondary endpoints will be conditional upon 
demonstrating success for the primary efficacy endpoint. The secondary 
endpoints of hospitalizations due to RSV and all-cause MA-LRTI will be 
tested in parallel so as to preserve the overall type 1 error across primary 
and secondary endpoint families at no more than 2.5% 1-sided. 
Multiplicity correction strategies will be defined in the SAP. VE for each 
secondary endpoint will be evaluated sequentially at 90 days, 120 days, 
150 days, and 180 days, as for the primary endpoint. Testing will only 
proceed to later time points conditional on success of all previous time
points. 

The infant evaluable efficacy population will be the primary population 
for efficacy analyses. The analysis will be repeated on the infant mITT 
efficacy population.
Exploratory

The incidence in infant participants of MA-RTIs due to RSV with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized.

The incidence in infant participants of MA-RTIs due to any cause with 
protocol-defined criteria occurring within 730 days after birth will be 
summarized. All MA-RTIs and severe MA-LRTIs will be summarized 
separately.

The primary endpoint through 181 days after birth will be summarized 
separately as cases associated with RSV subgroup A or RSV subgroup B 
infection.

The primary endpoint through 181 days after birth will be summarized by 
interval from vaccination to delivery and by GA at the time of 
vaccination.

The incidence of MA-RTI due to any cause in maternal participants from 
vaccination through 180 days after delivery will be summarized. 
Outcomes to be summarized will include all-cause MA-RTI, all-cause 
medically attended upper RTI, and all-cause MA-LRTI.

Variations on the primary and secondary endpoint definitions to include 
RSV positives from non–NAAT-based testing will be explored and 
summarized descriptively.
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9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

A 3-tier approach will be used to summarize AEs. For both Tier 1 and 
Tier 2 events, the 95% CIs for the difference in the percentage of 
participants reporting the events between the RSV vaccine group and the 
placebo group will be calculated using the test statistic proposed by 
Miettinen and Nurminen; in addition, for Tier 1 events, the asymptotic 
p-values will also be presented for the difference in the percentage of 
participants reporting the events, based on the same test statistic and under 
the assumption that the test statistic is asymptotically normally distributed.  
A Medical Dictionary for Regulatory Activities (MedDRA) preferred term 
is defined as a Tier 2 event if there are 1% or more participants in at least 
1 vaccine group reporting the event.

The safety analyses are based on the safety population. Participants will be 
summarized by the vaccine group corresponding to the vaccine they (for 
maternal participants) or their mothers (for infant participants) actually 
received. Missing e-diary data will not be imputed; missing AE dates and 
missing AE intensity will be addressed using the Pfizer safety rules.
Secondary

The point estimate and exact 2-sided 95% CI will be calculated using the 
Clopper-Pearson method for the percentage of participants reporting each 
event for each vaccine group.

The safety analyses are based on the safety population. Participants will be 
summarized by the vaccine group corresponding to the vaccine they (for 
maternal participants) or their mothers (for infant participants) actually 
received. Missing e-diary data will not be imputed; missing AE dates and 
missing AE intensity will be addressed using the Pfizer safety rules.
Exploratory

These analyses will be described in the SAP, finalized before first database 
lock.
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9.4.3. Other Analyses 
9.4.3.1. Immunogenicity Analyses
Immunogenicity endpoints are exploratory in the study.  The analyses of immunogenicity 
endpoints will be based on the evaluable populations.  An additional analysis will be 
performed based on the mITT populations if there is enough difference between the mITT
populations and the evaluable populations.  Immunogenicity data for maternal participants 
and infant participants will be summarized separately, with the exception of maternal-to-
infant placental transfer analysis.  Participants will be summarized according to the vaccine 
group to which they (for maternal participants) or their mothers (for infant participants) were 
randomized.
The secondary and exploratory immunogenicity endpoints will be described by the following 
summaries and the 95% CIs:

GMT of the RSV A– and RSV B–neutralizing antibody titers at each available time point 
by vaccine group (maternal participants and infant participants, separately).

GMT of the combined RSV A/B–neutralizing antibody titer, defined as the geometric 
mean of the RSV A– and RSV B–neutralizing antibody titers, at each available time point 
by vaccine group (maternal participants and infant participants, separately).

GMFR for RSV A– and RSV B–neutralizing antibody titers from before vaccination to 
each available time point after vaccination by vaccine group (maternal participants only).

GMFR of the combined RSV A/B–neutralizing antibody titer, defined as the geometric 
mean of the RSV A– and RSV B–neutralizing antibody titers, from before vaccination to 
each available time point after vaccination by vaccine group (maternal participants only).

GMR of the RSV vaccine group to the placebo group for the RSV A– and 
RSV B–neutralizing antibody titers at each available time point after vaccination 
(maternal participants and infant participants, separately).

GMR of the RSV vaccine group to the placebo group for the combined RSV A/B–
neutralizing antibody titers at each available time point after vaccination (maternal 
participants and infant participants, separately).

Geometric mean of the IgG levels against RSV prefusion F and Ig levels to nonvaccine 
RSV antigens at each available time point by vaccine group (maternal participants and 
infant participants, separately).

Geometric mean of IgG subclass levels (minimally IgG1) against RSV prefusion F at 
each available time point by vaccine group (maternal participants only).
Empirical reverse cumulative distribution curves (RCDCs) for combinations of time points 
and vaccine groups will be presented for RSV A– and RSV B–neutralizing antibody titers.
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A sensitivity analysis will be performed to exclude immunogenicity data from mothers and 
their infants following onset of RSV infection between vaccination and delivery (based on 
evidence from the nonvaccine antigen assay). 
Subgroup analyses of the secondary and exploratory immunogenicity endpoints will be 
performed, including an analysis based on GA at the time of vaccination, time from 
vaccination to delivery, and by country subcategories. All subgroup analyses will be defined 
in the SAP.
In addition, the maternal-to-infant placental transfer ratio (infant/mother) of RSV A– and 
RSV B–neutralizing antibody titers and associated 95% CI will be summarized.
9.4.3.2. Healthcare Utilization Analyses
Healthcare utilization endpoints are exploratory in the study; these analyses will be described 
in the SAP and finalized before first database lock. For these analyses, details of healthcare 
resource utilization for all infants will be assessed at each MA-RTI visit from birth through 
the last study visit (730 days after birth). Details of healthcare resource utilization will be 
summarized into a mean/median composite score, which may include the following: number 
and type (eg, respiratory, reactive airway disease [RAD]/asthma/wheezing) of medical visits 
(eg, outpatient, urgent care, emergency room, hospitalization, ICU), length of hospital stay, 
requirement for mechanical ventilation (yes/no, total number of episodes, total number of 
hours/days on treatment), requirement for IV fluids, requirement for respiratory diagnostic 
procedures (eg, chest radiograph, supplemental oxygen, pulse oximetry), requirement for 
prescriptions (eg, total number of prescriptions, selected respiratory medications [eg,
bronchodilators, corticosteroid therapy, racemic epinephrine]), and antibiotic use (eg, total 
number of prescriptions, number of use days).
9.5. Interim Analyses
An interim analysis may be performed to assess efficacy and safety after at least 50% of the 
planned number of cases of MA-LRTI due to RSV have occurred. Because of the relatively 
low number of cases of severe MA-LRTI due to RSV expected, the interim analysis will not 
consider that endpoint. Interim analysis results may be used for internal business decisions 
regarding future study planning, stopping for futility, stopping for early success, conducting a 
sample size reestimation, or adapting the study after the interim analysis.  
The order of cases included in the interim analysis will be determined by the adjudication 
committee as those first confirmed as meeting the protocol-defined criteria. When the target 
number of cases for the interim analysis is reached, it is possible that additional potential 
cases will be under adjudication. These additional cases will be included in the interim 
analysis only if confirmed as cases by the EAC on the same day that the last per-protocol 
case is confirmed.
The analysis of efficacy will utilize an O’Brien-Fleming alpha spending rule based on the 
fraction of cases of MA-LRTI due to RSV available. For example, to control the overall 
type 1 error for the primary endpoint at 2.5% 1-sided, an interim analysis at 50% of the target 
number of cases would use a nominal 1-sided significance level of 0.14%. The final analysis 
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at the target number of cases would use a nominal 1-sided significance level of 2.45%. The 
nominal alpha levels used at interim and final analyses will depend on the exact fraction of 
cases available at the interim analysis.
Testing of the primary endpoint at the interim analysis will follow the sequence of 
interval-specific tests as described in Section 9.4.1.  However, consideration will be given to 
stopping the study for efficacy only if all time intervals through 180 days indicate statistically 
significant efficacy. Secondary endpoints will not be tested at the interim analysis.
Futility will also be assessed using conditional power. Full details will be defined in the SAP. 
For example, if there are 62 cases available for the interim analysis, Table 8 indicates case 
splits for which stopping the study will be considered. The actual number of cases available 
may be slightly higher or lower than 62, and the decision rules amended accordingly.
Table 8.
Example of Estimated Vaccine Efficacy and Confidence Intervals at an 
Interim Analysis
Total Cases
RSV Vaccine 
Group Cases
Placebo Group 
Cases
VE (CI)a
Notes
62
29
33
12% (-49%, 49%)
Conditional power 
<20%b; possible 
futility declaration
62
15
47
68% (24%, 88%)
Maximum number 
of RSV cases 
permitted to 
declare VE >20%
Abbreviation: VE = vaccine efficacy.
a. 99.7% confidence level for efficacy declaration; 95% confidence level for futility.
b. Other conditional power levels may be considered as a trigger for a futility decision.
Before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan, and method of maintaining the study blind as per Pfizer’s standard 
operating procedures (SOPs) will be documented and approved in the DMC charter.  In 
addition, the analysis details must be documented and approved in an interim analysis SAP 
or final SAP.
9.5.1. Data Monitoring Committee 
This study will use an E-DMC.  Refer to the E-DMC charter for further details.
The E-DMC will review safety data at defined intervals as specified in the charter.  The 
E-DMC may conduct additional meetings to review safety data at other time points during 
the study, at its discretion, or at the request of the sponsor.
The E-DMC may review unblinded data during closed meeting sessions; however, the 
sponsor will remain blinded and will not be permitted access to the randomization 
assignments until the database is locked and unblinded.
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After each meeting, the E-DMC will make recommendations that may include continuing the 
study with or without modification or pausing or stopping vaccination for safety or other 
reasons.
The E-DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data that are not endpoints, to regulatory authorities, as appropriate.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, IB, and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and
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of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities.  Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the maternal 
participant and answer all questions regarding the study.
Maternal participants must be informed that their participation is voluntary.  Maternal 
participants will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability 
and Accountability Act (HIPAA) requirements, where applicable, and the IRB/EC or study 
center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the maternal participant.
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Before any study-specific activity is performed, the investigator, or a person designated by 
the investigator, will obtain written informed consent from each maternal participant.  This 
will include written informed consent for the mother and the fetus during the pregnancy, and 
the infant’s continuation in the study after delivery.  Informed consent will be obtained from 
the father of the fetus/infant if mandated by local requirements.
Participants who are rescreened may be required to sign a new ICD as per IRB, local 
regulations, etc.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.  
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred.  All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code.  The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity.  In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
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product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (clinical study report [CSR] synopses in which any 
data that could be used to identify individual participants have been removed) on 
www.pfizer.com for Pfizer-sponsored interventional studies at the same time the US Basic 
Results document is posted to www.clinicaltrials.gov.
Documents Within Marketing Authorization Packages/Submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class.  Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses.  Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
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10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data).  The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan/contracts.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during 
the retention period without the written approval of the sponsor.  No records may be 
transferred to another location or party without written notification to the sponsor.  The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
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The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the site Source Data Agreement 
Plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon 
study completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
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10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study (or 
study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
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number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
For maternal immunization clinical studies conducted in pregnant women, data on the EDP 
as well as pregnancy outcome are collected and analyzed in the clinical database.  For these 
studies, in general, EDP cases are not reportable unless associated with SAEs/nonserious 
AEs.
The term “participant” in this section refers to (1) the maternal participant and her fetus; and 
after delivery (2) the maternal participant and (3) the infant participant.
10.2.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.2.2. Newly Diagnosed Chronic Medical Conditions (NDCMCs)
An NDCMC is defined as a disease or medical condition, not previously identified, that is 
expected to be persistent or otherwise long-lasting in its effects (eg, asthma).
10.2.3. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or treatment 
that would not have been appropriate in the physician’s office or outpatient setting.  
Complications that occur during hospitalization are AEs.  If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious.  When in doubt as to 
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whether “hospitalization” occurred or was necessary, the AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition.  These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization, or development of drug dependency or drug abuse.
10.2.4. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the CT SAE Report Form to Pfizer Safety.  These requirements are 
delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and (3) occupational 
exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
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Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study via 
occupational exposure
None
Occupational exposure 
(regardless of whether 
associated with an AE)  

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the CT SAE Report Form/AE/SAE CRF 
page.

There may be instances when copies of medical records for certain cases are requested by 
Pfizer Safety.  In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to Pfizer 
Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories: 
GRADE If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING to 
describe the maximum intensity of the AE. For purposes of consistency, 
these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
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3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent intervention 
indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the sponsor.  However, it is very important 
that the investigator always make an assessment of causality for every event before 
the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused the 
event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the sponsor.  In addition, if the investigator determines that an 
SAE is associated with study procedures, the investigator must record this causal 
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relationship in the source documents and CRF, and report such an assessment in the 
dedicated section of the CT SAE Report Form and in accordance with the SAE reporting 
requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor to 
elucidate the nature and/or causality of the AE or SAE as fully as possible.  This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any anonymized 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.2.5. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic data 
collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data become 
available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
off-line, then the site can report this information on a paper SAE form (see next section) 
or to Pfizer Safety by telephone.
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SAE Reporting to Pfizer Safety via CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is the preferred method to transmit 
this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or courier 
service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting time 
frames.
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10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI). Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a 
participant presents with clinical signs/symptoms, such LFT results should be managed and 
followed as described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
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
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.4. Appendix 4: Medical Device Incidents: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Incident
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.4) for the list of sponsor 
medical devices.
Medical Device Incident Definition
a.
A medical device incident is any malfunction or deterioration in the characteristics and/or 
performance of a device as well as any inadequacy in the labeling or the instructions for 
use which, directly or indirectly, might lead to or might have led to the death of a 
participant/user/other person or to a serious deterioration in his/her state of health.
b. Not all incidents lead to death or serious deterioration in health.  The nonoccurrence of 
such a result might have been due to other fortunate circumstances or to the intervention 
of healthcare personnel.
It is sufficient that:

An incident associated with a device happened.
AND

The incident was such that, if it occurred again, might lead to death or a serious 
deterioration in health.
A serious deterioration in state of health can include any of the following:

Life-threatening illness;

Permanent impairment of body function or permanent damage to body structure;

Condition necessitating medical or surgical intervention to prevent one of the above;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
Examples of Incidents
a.
A participant, user, caregiver, or healthcare professional is injured as a result of a medical 
device failure or its misuse.
b. A participant’s study intervention is interrupted or compromised by a medical device 
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failure.
c.
A misdiagnosis due to medical device failure leads to inappropriate treatment.
d. A participant’s health deteriorates due to medical device failure.
Documenting Medical Device Incidents
Medical Device Incident Documentation
a.
Any medical device incident occurring during the study will be documented in the 
participant’s medical records, in accordance with the investigator’s normal clinical 
practice, and on the appropriate form of the CRF.
b. For incidents fulfilling the definition of an AE or an SAE, the appropriate AE/SAE CRF 
page will be completed as described in Appendix 2.
c.
The CRF will be completed as thoroughly as possible and signed by the investigator 
before transmittal to the sponsor or designee.
d. It is very important that the investigator provides his/her assessment of causality 
(relationship to the medical device provided by the sponsor) at the time of the initial AE
or SAE report and describes any corrective or remedial actions taken to prevent 
recurrence of the incident.
e.
A remedial action is any action other than routine maintenance or servicing of a medical 
device where such action is necessary to prevent recurrence of an incident.  This includes 
any amendment to the device design to prevent recurrence.
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10.5. Appendix 5: Background Factors
1. Information on the following will be collected at Visit 1 for all infant participants:

Educational level of parent(s) or legal guardian(s)

Exposure to smoke (including tobacco smoke)

Number of persons in the household

Number of children in the household and if they attend school

Number of children in the household under 5 years of age (under 60 months)

Number of children in the household 5 years of age (60 months)
2. Information on the following will be collected at each postbirth visit, and at each 
MA-RTI visit:

Childcare framework (for infant participants)

Breastfeeding information (including whether or not breastfeeding is exclusive)

Number of missed days of work for parent(s) or legal guardian(s) due to the infant 
participant’s illness
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10.6. Appendix 6: Healthcare Provider Assessment and Treatment Criteria Checklist 
for MA-RTI Visit – Infant Participants
When an infant RTI medical visit criterion is met or confirmed, the site will obtain records 
from the medical visit and capture the healthcare information as detailed below in the eCRF. 
This information is based on respiratory-related assessments including examination findings, 
clinical findings, and any pathogen-related assessments/findings. 
Medical Visit - visit details and assessment requirements
Note: This should not be linked to a study visit but may overlap with the MA-RTI 
assessment visit. The following fields and clinical assessment details should be obtained 
from relevant records for the medically attended event prior to each study-related MA-RTI 
assessment visit to support the assessment of the RTI event.

Reason for visit including date/time, eg,
o
Nasal discharge for 24 hours or more.
o
Difficulty breathing, labored breathing, or rapid breathing for any duration.
o
Cough.
o
Inability to feed for any duration due to respiratory symptoms.
o
Any other respiratory symptom of concern (eg, apnea).

Location of medical visit (inpatient clinic, outpatient clinic, emergency department, 
urgent care, hospitalization, home visit, other). Note: study visits should NOT be 
recorded here.
o
If hospital visit, was this triggered by RTI or an SAE? (include details if associated 
with prolongation of hospitalization at birth). Provision of admission and discharge 
information and records, including ICU details.

Clinical findings pertaining to respiratory symptoms and/or RTI, as detailed below but 
not limited to:
o
Presence or absence of respiratory examination findings, eg, chest wall indrawing, 
intercostal retractions, apnea (documented as per chart), failure to 
respond/unconsciousness. 
o
Respiratory rate from highest/worst value of visit.
o
Oxygen saturation (SpO2) from lowest/worst value of visit.
o
Altitude (select >1800 m OR ≤1800 m).
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o
Oxygen supplementation (assisted ventilation, including type of respiratory assistance 
[respirator, “state-of-the-art” occlusive nasal prongs, face tent, etc]).

Days of supplementary oxygen.

Use of nasal cannula.

Use of high-flow nasal cannula or mechanical ventilation (ie, invasive or 
noninvasive).
o
Heart rate from worst value of visit when performed consistently.
o
Additional clinical or respiratory related assessments including chest x-ray 

Local test results for RSV as part of routine clinical care:
o
Testing platform used (clinical list of all platforms and validated by research).
o
Result (list: positive, negative, indeterminate, other).

Obtain details of all prescribed medications including IV fluid usage.

Obtain details of all AEs/SAEs in line with study requirements. Note: MA-RTIs are not 
AEs/SAEs.
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10.7. Appendix 7: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
Apgar
appearance, pulse, grimace, activity, and respiration
AST
aspartate aminotransferase
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLIA
Clinical Laboratory Improvement Amendments
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EAC
endpoint adjudication committee
EACC
endpoint adjudication committee charter
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine 
GA
gestational age
GBS
group B streptococcal
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
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Abbreviation
Term
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBIG
hepatitis B immune globulin
HBV
hepatitis B virus
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
IAP
intrapartum antibiotic prophylaxis
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
Ig
immunoglobulin
IgG
immunoglobulin G
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IRT
interactive response technology
ISF
investigator site file
IUI
intrauterine insemination
IV
intravenous
IWR
interactive Web-based response
LFT
liver function test
LMIC
lower- and middle-income country
LMP
last menstrual period
LRTI
lower respiratory tract illness
MA-LRTI
medically attended lower respiratory tract illness
MA-RTI
medically attended respiratory tract illness
MCAR
missing completely at random
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NAAT
nucleic acid amplification technology
NDCMC
newly diagnosed chronic medical condition
PCD
primary completion date
PCR
polymerase chain reaction
PFS
prefilled syringe
PT
prothrombin time
RAD
reactive airway disease
RCDC
reverse cumulative distribution curve
RSV
respiratory syncytial virus
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Abbreviation
Term
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RTI
respiratory tract illness
RT-PCR
reverse transcription–polymerase chain reaction
SAE
serious adverse event
SAP
statistical analysis plan
SMS
short message service
SoA
schedule of activities
SOP
standard operating procedure 
SpO2
oxygen saturation
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Tdap
tetanus, diphtheria, and acellular pertussis vaccine
ULN
upper limit of normal
US
United States
VE
vaccine efficacy
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11. REFERENCES
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27
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World_Vaccine_Congress/2019.04.16-World_Vaccine_Congress.pdf. Accessed: 25 Nov 
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29     Regen AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization 
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30     Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: case definition & guidelines for 
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European Commission. Ethical considerations for clinical trials on medicinal products 
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