A PHASE 2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A SARS-COV-2 RNA VACCINE CANDIDATE (BNT162b2) AGAINST COVID-19 IN HEALTHY PREGNANT WOMEN 18 YEARS OF AGE AND OLDER
Phase: PHASE2
Conditions: SARS-CoV-2 Infection, COVID-19, Maternal Immunization
Sponsor: BioNTech SE

PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591015
Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
Page 1
A PHASE 2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND 
STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND 
IMMUNOGENICITY OF A SARS-COV-2 RNA VACCINE CANDIDATE 
(BNT162b2) AGAINST COVID-19 IN HEALTHY PREGNANT WOMEN 18 YEARS 
OF AGE AND OLDER
Study Sponsor:
Study Conducted By: 
Study Intervention Number:
BioNTech
Pfizer
PF-07302048
Study Intervention Name:
RNA-Based COVID-19 Vaccines
US IND Number:
19736
EudraCT Number:
2020-005444-35
Protocol Number:
C4591015
Phase:
Phase 2/3
Short Title: A Phase 2/3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of 
SARS-CoV-2 RNA Vaccine Candidate (BNT162b2) Against COVID-19 in Healthy 
Pregnant Women 18 Years of Age and Older
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-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591015
Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Protocol amendment 5
08 March 2022
•
Enrollment of study participants was 
terminated with fewer study participants 
enrolled than originally planned due to 
enrollment challenges into a 
placebo-controlled trial as a result of 
universal recommendations for 
COVID-19 vaccination of pregnant 
women and the increased global 
availability of COVID-19 vaccines.
•
Modified the primary immunogenicity 
objectives and estimands from 
hypothesis testing analysis to descriptive 
analysis as a result of the significantly 
reduced final number of study 
participants enrolled than originally 
planned.
•
Modified an exploratory 
immunogenicity estimand by removing 
the calculation of incidence rate after 
1 month after delivery for crossover 
participants because there is no 
COVID-19 surveillance for these 
participants after 1 month after delivery.
•
Modified appropriate statistical sections 
due to updates to the primary 
immunogenicity objectives and 
estimands.
•
Updated Sections 2.2.1 and 2.3 to reflect 
current recommendations and to provide 
details of the recent safety and efficacy 
analysis results for study C4591001.
Protocol amendment 4
06 August 2021
•
Added procedures in Section 8.14 to 
capture data pertaining to myocarditis 
and pericarditis in response to 
commitments made to CBER.
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591015
Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
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Document History
Document
Version Date
Summary and Rationale for Changes
•
Added myocarditis and pericarditis in 
Sections 8.14 and 2.3.1 in response to 
commitments made to CBER.
•
Added a procedure to any visit that 
occurs sooner than 1 month after any 
vaccination in Sections 8.11 and 8.17 in 
response to commitments made to 
CBER.
•
Added myocarditis and pericarditis as 
AESIs in Section 8.3.8.
•
Added a statement on diversity in 
Section 5.
•
Added clarification to the infant SoA 
(Section 1.3.3) to collect the e-diary or 
assist the maternal participant to delete 
the application at Visit 3.
•
Administrative update in 
Section 8.11.1.7 to add collection of the 
e-diary or assist the participant to delete 
the application.
•
Corrected typographical errors 
throughout.
Protocol amendment 3
14 May 2021
•
Reduced the study sample size based on 
regulatory feedback and evolving global 
availability of COVID-19 vaccines for 
pregnant women.
•
Modified the study objectives to align 
with the reduced sample size.
•
Removed the hypothesis-based efficacy 
objective, estimands, and endpoints.
•
Modified the statistical analysis timing 
to align with the reduced sample size 
and changes in the objectives.
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
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Document History
Document
Version Date
Summary and Rationale for Changes
•
Updated a typographical error in the 
SoA regarding the need to collect AE 
information during the 1-week 
postdelivery follow-up call.
•
Clarified that, if pregnancy outcome 
information was not obtained at the time 
of delivery, updated information should 
be provided at Visit 6.
•
Added a modifier to inclusion 
criterion 8 regarding the need for a 
telephone as method of contact in 
Mozambique, so that the population is 
reachable based on location despite lack 
of routine access to telephones.
•
Removed the collection of CD4 count 
and HIV viral load at Visit 101 in 
Sections 1.3.2 and 8.17.1 since this is 
duplicate information and will already 
be collected at Visit 7 in Section 1.3.1.
•
Added “chills” to the definition of 
confirmed COVID-19 in maternal 
participants in Section 8.1.1.
Protocol amendment 2
02 March 2021
•
Sections 1.3.1 and 1.3.2: expanded the 
1-month postdelivery visit window by 
1 week to allow for potential earlier 
vaccination of BNT162b2 to 
participants originally randomized to 
receive placebo.
•
Section 1.3.3: removed “equivalent visit 
number for maternal participants” from 
the Infant SoA since this will differ for 
maternal participants originally 
randomized to placebo who will go on 
to receive BNT162b2 at 1 month after 
delivery and follow a different SoA.
•
Section 2.3: added a sentence to clarify 
that the protocol is a PASS.
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
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Document History
Document
Version Date
Summary and Rationale for Changes
•
Section 5.1.1: corrected the calculation 
of GA in the third trimester, 
replacing “second trimester” with 
“third trimester,” and updated the 
discrepancy of days between the 
LMP-determined GA from >10 to >21 
days.
•
Removed references to 
thumbprinting the ICD, since 
illiterate participants will not be 
enrolled from certain regions.
•
Clarified in Section 8.2.2 that field 
workers would be used in the case of 
poor network connection for e-diary 
completion.
•
Sections 5.1.1, 8.17.3, and 10.4: added 
criteria for inclusion of maternal 
participants with stable HIV, 
hepatitis B, or hepatitis C in Phase 3.
•
Updated the Objectives, Estimands, and 
Endpoints to add a safety objective for 
the first 600 randomized maternal 
participants to support interim 
analysis/submission report.
•
Per CBER feedback, updated the 
term “NI” to “immunobridging” to
describe the immunogenicity 
comparison between nonrandomized 
populations in the protocol.
•
Added a footnote to clarify that 
HIV-infected participants will not be 
included in analyses of the 
objectives. Analyses among 
HIV-infected women and their 
infants will be summarized 
separately.
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Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
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•
Sections 8.1.1 and 8.13.1: added a 
second definition of symptoms of severe 
COVID-19 disease per the CDC 
definition.
•
Section 8.2.3: clarified that stopping 
rules are in place during Phase 2 only, 
with no overlap into Phase 3.
•
Clarified that a study pause may not 
prevent administration of Dose 2 for 
enrolled participants.
•
Modified stopping rule 7 to include 
a trigger of preterm premature 
rupture of membranes.
•
Stopping rule 4: removed 
assessment of laboratory 
abnormalities, as these data are not 
collected in this study.
•
Section 8.11.1, Visit 1: removed the 
requirement of a repeat fetal scan 
to clarify that an earlier scan done 
at ≥18 weeks瀠GA can be used to 
confirm singleton pregnancy and rule 
out fetal anomalies.
•
Section 8.16: clarified that exclusion 
criterion 2 is not met if the participant 
meets the criteria for confirmed 
COVID-19 with or without symptoms 
and can receive Vaccination 2.
•
Section 8.17: to align with current 
recommendations, investigators may 
exercise judgment on review of 
inclusion and exclusion criteria ahead of 
vaccination with BNT162b2 for 
participants who originally received 
placebo.
•
Sections 8.3.1 and 8.3.7: inserted 
language to clarify that potential 
COVID-19/MIS-C illnesses and their 
sequelae that are consistent with the 
clinical endpoint definition should not 
be recorded as AEs.
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Document History
Document
Version Date
Summary and Rationale for Changes
•
Appendix 3: removed an erroneous 
partially completed sentence from the 
second paragraph.
Protocol amendment 1
28 January 2021
•
Based on availability of BNT162b2 in 
high-risk pregnant women and evidence 
of safety in the real-world setting, the 
sentinel cohort of N=50 in Phase 2 was 
removed.
•
Based on feedback from an external 
advisory board, inclusion criterion 10 
was updated to allow enrollment of 
participants with a prepregnancy BMI 
of ≤40 kg/m2.
•
Clarified language in inclusion 
criterion 1 that GA dating for maternal 
participants who underwent assisted 
reproduction technology can be 
referenced in the SRM.
•
Corrected the list of prohibited 
medications under Section 6.5.1.
•
Clarified language in the Objectives, 
Estimands, and Endpoints table for 
consistency.
•
Added exploratory objectives to 
evaluate incidence rates of COVID-19 
and asymptomatic SARS-CoV-2 
infection through the entire follow-up 
among the maternal participants 
receiving BNT162b2.
•
Updated the VE assessment to reflect 
the reduced accrual of time following 
the unblinding of participants at 1 month 
after delivery.
•
Clarified the unblinding at 1 month after 
delivery for participants originally 
randomized to placebo who go on to 
receive BNT162b2.
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
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Document History
Document
Version Date
Summary and Rationale for Changes
•
Updated Section 2.3, Benefit-Risk 
Assessment, to include data from the 
DART studies.
•
In line with current recommendations, 
removed the requirement to discontinue 
study intervention because of a 
diagnosis of COVID-19 during the 
study.
•
Added the requirement to record 
antipyretic medication in the e-diary 
during the 7-day vaccination period, as 
this was omitted in error.
•
Added editorial changes in the 
document to clarify where field 
workers/site staff may be required to 
call/visit maternal participants at home 
(applicable to regions where illiterate 
participants may be enrolled).
•
Clarified that participants originally 
randomized to placebo who go on to 
receive BNT162b2 at 1 month after 
delivery will not participate in 
COVID-19 surveillance.
•
Clarified that AEs will be collected from 
the signing of the ICD to 1 month after 
Vaccination 4 (Visit 103) for those 
maternal participants who originally 
received placebo and who go on to 
receive BNT162b2 at 1 month after 
delivery.
Original protocol
21 December 2020
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs.
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Final Protocol Amendment 5, 08 March 2022
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................15
1. PROTOCOL SUMMARY...................................................................................................16
1.1. Synopsis ..................................................................................................................16
1.2. Schema ....................................................................................................................22
1.3. Schedule of Activities .............................................................................................23
1.3.1. Schedule of Activities for Maternal Participants........................................23
1.3.2. Schedule of Activities for Maternal Participants Who Were 
Originally Assigned to Placebo .......................................................................28
1.3.3. Schedule of Activities for Infant Participants.............................................29
2. INTRODUCTION ...............................................................................................................30
2.1. Study Rationale .......................................................................................................30
2.2. Background .............................................................................................................30
2.2.1. Clinical Overview.......................................................................................31
2.3. Benefit/Risk Assessment.........................................................................................34
2.3.1. Risk Assessment.........................................................................................36
2.3.2. Benefit Assessment.....................................................................................39
2.3.3. Overall Benefit/Risk Conclusion................................................................39
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................39
4. STUDY DESIGN.................................................................................................................43
4.1. Overall Design.........................................................................................................43
4.2. Scientific Rationale for Study Design.....................................................................44
4.3. Justification for Dose ..............................................................................................44
4.4. End of Study Definition ..........................................................................................45
5. STUDY POPULATION......................................................................................................45
5.1. Inclusion Criteria.....................................................................................................45
5.1.1. Maternal Participants..................................................................................45
5.1.2. Infant Participants.......................................................................................47
5.2. Exclusion Criteria....................................................................................................48
5.2.1. Maternal Participants..................................................................................48
5.2.2. Infant Participants.......................................................................................50
5.3. Lifestyle Considerations..........................................................................................50
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5.4. Screen Failures ........................................................................................................50
5.5. Criteria for Temporarily Delaying Randomization/Study Intervention 
Administration...........................................................................................................50
6. STUDY INTERVENTION..................................................................................................51
6.1. Study Intervention(s) Administered........................................................................52
6.1.1. Administration............................................................................................52
6.2. Preparation/Handling/Storage/Accountability ........................................................53
6.2.1. Preparation and Dispensing........................................................................54
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................54
6.3.1. Allocation to Study Intervention ................................................................54
6.3.2. Blinding of Site Personnel Until the 1-Month Postdelivery Visit ..............55
6.3.3. Blinding of Site Personnel Prior to the 1-Month Postdelivery Visit ..........55
6.3.4. Blinding of the Sponsor..............................................................................56
6.3.5. Breaking the Blind......................................................................................57
6.4. Study Intervention Compliance...............................................................................57
6.5. Concomitant Therapy..............................................................................................57
6.5.1. Prohibited During the Study – Maternal Participants.................................57
6.5.2. Permitted During the Study – Maternal Participants..................................58
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications –
Maternal Participants .......................................................................................58
6.5.4. Prohibited During the Study – Infant Participants......................................58
6.5.5. Permitted During the Study – Infant Participants.......................................58
6.5.6. Recording Concomitant Medications – Infant Participants........................59
6.6. Dose Modification...................................................................................................59
6.7. Intervention After the End of the Study..................................................................59
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................59
7.1. Discontinuation of Study Intervention ....................................................................59
7.2. Participant Discontinuation/Withdrawal From the Study.......................................60
7.2.1. Withdrawal of Consent...............................................................................61
7.3. Lost to Follow-up....................................................................................................61
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................61
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8.1. Efficacy and/or Immunogenicity Assessments .......................................................63
8.1.1. Maternal Participants..................................................................................63
8.1.2. Infant Participants.......................................................................................65
8.1.3. Immunogenicity..........................................................................................67
8.1.4. Total Volume of Blood Collected – Maternal Participants ........................68
8.1.5. Total Volume of Blood Collected – Infant Participants .............................68
8.1.6. Biological Samples.....................................................................................68
8.2. Safety Assessments .................................................................................................69
8.2.1. Clinical Safety Laboratory Assessments ....................................................69
8.2.2. Electronic Diary..........................................................................................69
8.2.2.1. Grading Scales...........................................................................70
8.2.2.2. Local Reactions.........................................................................70
8.2.2.3. Systemic Events ........................................................................71
8.2.2.4. Fever..........................................................................................73
8.2.2.5. Antipyretic Medication .............................................................74
8.2.3. Stopping Rules............................................................................................74
8.2.4. Surveillance of Events That Could Represent Enhanced COVID-19 ........75
8.2.5. Clinical Safety Laboratory Assessments ....................................................75
8.3. Adverse Events and Serious Adverse Events..........................................................75
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......76
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................77
8.3.1.2. Recording Nonserious AEs and SAEs in the CRF....................78
8.3.2. Method of Detecting AEs and SAEs ..........................................................78
8.3.3. Follow-up of AEs and SAEs.......................................................................78
8.3.4. Regulatory Reporting Requirements for SAEs...........................................79
8.3.5. Additional Exposure Scenarios That May Result From the Exposure 
to the Study Intervention..................................................................................79
8.3.5.1. Environmental Exposure During Pregnancy.............................79
8.3.5.2. Exposure During Breastfeeding ................................................81
8.3.5.3. Occupational Exposure .............................................................81
8.3.6. Cardiovascular and Death Events...............................................................81
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8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................81
8.3.8. Adverse Events of Special Interest.............................................................82
8.3.8.1. Lack of Efficacy........................................................................82
8.3.9. Medical Device Deficiencies......................................................................83
8.3.10. Medication Errors.....................................................................................83
8.4. Treatment of Overdose............................................................................................84
8.5. Pharmacokinetics ....................................................................................................84
8.6. Pharmacodynamics..................................................................................................84
8.7. Genetics...................................................................................................................84
8.8. Biomarkers ..............................................................................................................84
8.9. Immunogenicity Assessments.................................................................................84
8.10. Health Economics .................................................................................................84
8.11. Study Procedures – Maternal Participants ............................................................85
8.11.1. Visit 1: Screening (-28 Days to Vaccination 1)........................................85
8.11.1.1. Visit 2 – Vaccination 2 (Clinic: 19-23 Days After 
Vaccination 1) ...................................................................................88
8.11.1.2. Visit 3 – 2-Week Postvaccination Follow-up (Clinic)............90
8.11.1.3. Visit 4 – 1-Month Postvaccination Follow-up Visit 
(Clinic: 28-35 Days After Visit 2).....................................................90
8.11.1.4. Visit 5 – Delivery....................................................................91
8.11.1.5. Visit 6 – 1-Week Postdelivery Follow-up (Telephone 
Call: 7-10 Days After Delivery)........................................................92
8.11.1.6. Visit 7 – 1-Month Postdelivery Follow-up (Clinic: 21 to 
35 Days After Delivery) ....................................................................93
8.11.1.7. Visit 8 – 6-Month Postdelivery Follow-up (Clinic: 
160-200 Days After Delivery)...........................................................93
8.12. Unscheduled Visit for Reactogenicity Events.......................................................94
8.13. COVID-19 Surveillance (All Maternal Participants)............................................95
8.13.1. Potential Maternal COVID-19 Illness Visit (Optimally Within 
3 Days After Potential COVID-19 Illness Onset)............................................96
8.13.2. Potential Maternal COVID-19 Convalescent Visit (28 to 35 Days 
After Potential  COVID-19 Illness Visit) ........................................................98
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8.14. Additional Procedures for Monitoring of Potential Myocarditis or 
Pericarditis.................................................................................................................98
8.15. Communication and Use of Technology...............................................................99
8.16. SARS-CoV-2 NAAT Results From Visits 1 and 2 and Potential COVID-19 
Illness Visits ..............................................................................................................99
8.17. Procedures for Administration of BNT162b2 to Those Originally Assigned 
to Placebo ................................................................................................................100
8.17.1. Visit 101 – Vaccination 3 – 1-Month Postdelivery Follow-up
(Clinic: 21 to 35 Days After Delivery) ..........................................................100
8.17.2. Visit 102 – Vaccination 4 (19 to 23 Days After Visit 101)....................101
8.17.3. Visit 103 – 1-Month Follow-up Telephone Contact (After 
Vaccination 4) (28 to 35 Days After Visit 102).............................................102
8.18. Study Procedures – Infant Participants ...............................................................103
8.18.1. Infant Participants: Visit 1 – Delivery....................................................103
8.18.2. Visit 2 – 1-Week Postdelivery Follow-up (Telephone Call: 
7-10 Days After Visit 1) ................................................................................104
8.18.3. Visit 3 – 6-Months-of-Age Follow-up (Clinic: 160-200 Days After 
Visit 1) ...........................................................................................................104
8.19. COVID-19 Surveillance (All Infant Participants)...............................................105
8.19.1. Potential Infant COVID-19/MIS-C Illness Visit (Optimally Within 
3 Days After Potential COVID-19 Illness Onset)..........................................105
8.19.2. Potential Infant COVID-19 Convalescent Visit (28 to 35 Days 
After Potential COVID-19 Illness Visit) .......................................................107
9. STATISTICAL CONSIDERATIONS ..............................................................................108
9.1. Estimands and Statistical Hypotheses...................................................................108
9.1.1. Estimands..................................................................................................108
9.1.2. Statistical Hypotheses...............................................................................108
9.2. Sample Size Determination...................................................................................108
9.3. Analysis Sets .........................................................................................................109
9.4. Statistical Analyses ...............................................................................................110
9.4.1. General Considerations.............................................................................110
9.4.1.1. Analyses for Binary Data ........................................................110
9.4.1.2. Analyses for Continuous Data.................................................111
9.4.2. Primary Endpoint(s)..................................................................................111
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9.4.3. Secondary Endpoint(s)..............................................................................112
9.4.4. Exploratory Endpoint(s) ...........................................................................113
9.5. Interim Analyses ...................................................................................................114
9.5.1. Analysis Timing........................................................................................114
9.6. Data Monitoring Committee or Other Independent Oversight Committee...........115
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................116
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............116
10.1.1. Regulatory and Ethical Considerations ..................................................116
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................116
10.1.2. Financial Disclosure ...............................................................................117
10.1.3. Informed Consent Process ......................................................................117
10.1.4. Data Protection .......................................................................................118
10.1.5. Dissemination of Clinical Study Data ....................................................118
10.1.6. Data Quality Assurance ..........................................................................120
10.1.7. Source Documents..................................................................................121
10.1.8. Study and Site Start and Closure ............................................................121
10.1.9. Publication Policy...................................................................................122
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................123
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................124
10.2.1. Definition of AE .....................................................................................124
10.2.2. Definition of SAE...................................................................................125
10.2.3. Recording/Reporting and Follow-up of AEs and/or SAEs.....................127
10.2.4. Reporting of SAEs..................................................................................129
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-up Assessments ......131
10.4. Appendix 4: Criteria for Allowing Inclusion of Participants With Chronic 
Stable HIV, HCV, or HBV Infection ......................................................................133
10.5. Appendix 5: Abbreviations .................................................................................134
11. REFERENCES ................................................................................................................138
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LIST OF TABLES
Table 1.
Guideline for Infant Blood Draw, if Cord Blood Sample Was Not 
Obtained....................................................................................................68
Table 2.
Local Reaction Grading Scale ..................................................................71
Table 3.
Systemic Event Grading Scale..................................................................72
Table 4.
Scale for Fever..........................................................................................73
Table 5.
Probability of Observing at Least 1 AE by Assumed True Event 
Rates With Different Sample Sizes ........................................................109
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1. PROTOCOL SUMMARY
1.1. Synopsis
Short Title: A Phase 2/3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 
SARS-CoV-2 RNA Vaccine Candidate (BNT162b2) Against COVID-19 in Healthy 
Pregnant Women 18 Years of Age and Older
Rationale
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China.  
In January 2020, it became clear that a novel coronavirus (2019-nCoV) was the underlying 
cause.  Later in January, the genetic sequence of the 2019-nCoV became available to the 
WHO and public (MN908947.3), and the virus was categorized in the Betacoronavirus
subfamily.  By sequence analysis, the phylogenetic tree revealed a closer relationship to 
SARS virus isolates than to another coronavirus infecting humans, the MERS virus. 
SARS-CoV-2 infections and the resulting disease, COVID-19, have spread globally, 
affecting a growing number of countries.
On 11 March 2020, the WHO characterized the COVID-19 outbreak as a pandemic.  Global 
case rates and deaths have continued to increase, with the United States reporting the most
cases and deaths of any other country.  At the time of this communication, the number of 
confirmed cases continues to rise globally.  There are currently no licensed vaccines or 
effective antiviral drugs to prevent SARS-CoV-2 infections or the disease it causes, 
COVID-19.
Pregnant women are at risk for acquiring SARS-CoV-2 infection and COVID-19. Pregnancy 
may confer increased risk of severe COVID-19 because of physiological changes during 
pregnancy that can increase susceptibility to respiratory infections and subsequent rapid 
progression to respiratory failure. Additionally, pregnant women with COVID-19 have been 
reported to have higher rates of preterm birth, cesarean delivery, fetal distress, and infants 
requiring neonatal intensive care. Prevention of SARS-CoV-2 infection and COVID-19 is 
critically important in pregnant women.
Given the rapid transmission of COVID-19 and incidence of disease in the United States and 
elsewhere, the rapid development of an effective vaccine is of utmost importance.
BNT162b2 is a SARS-CoV-2–RNA-LNP vaccine based on a platform of modRNA with 
blunted innate immune sensor–activating capacity and augmented expression encoding the
P2 S.
This study will describe the safety of BNT162b2 in pregnant women and their infants. It will 
also assess the immunogenicity of BNT162b2 in pregnant women, the transfer of antibody to 
their infants, and the kinetics of antibody transfer in the infant.
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Objectives, Estimands, and Endpoints
Objectivesa
Estimands
Endpoints
Primary Safety
Primary Safety
Primary Safety
To describe the safety and 
tolerability of prophylactic 
BNT162b2 when 
administered to maternal 
participants 18 years of age 
or older vaccinated at 24 to 
34 weeks’ gestation.
In maternal participants receiving 
at least 1 dose of study 
intervention from each vaccine 
group, the percentage of maternal 
participants reporting:
•
Local reactions for up to 
7 days following each dose
•
Systemic events for up to 
7 days following each dose
•
AEs from Dose 1 through
1 month after Dose 2
•
SAEs from Dose 1 through
1 month after delivery
•
Prompted local reactions (redness, 
swelling, and pain at the injection 
site)
•
Prompted systemic events (fever, 
fatigue, headache, chills, vomiting, 
diarrhea, new or worsened muscle 
pain, and new or worsened joint 
pain)
•
AEs
•
SAEs
Primary Immunogenicity
Primary Immunogenicity
Primary Immunogenicity
To describe the immune 
response to prophylactic 
BNT162b2 in maternal 
participants 18 years of age 
or older vaccinated at 24 to 
34 weeks’ gestation and
reference to the immune 
response in nonpregnant 
women 18 years of age or 
older from the C4591001 
study without evidence of 
past SARS-CoV-2 infection.
In female participants complying 
with the key protocol criteria 
(evaluable participants) and no 
serological or virological
evidence (up to 1 month after 
receipt of the second dose) of 
past SARS-CoV-2 infection:
•
GMR, estimated by the ratio 
of the geometric mean of 
SARS-CoV-2 neutralizing 
titers in pregnant women to 
those in nonpregnant women 
1 month after Dose 2
•
SARS-CoV-2 neutralizing titers
To describe the immune 
response to prophylactic 
BNT162b2 in maternal 
participants 18 years of age 
or older vaccinated at 24 to 
34 weeks’ gestation and
reference to the immune 
response in nonpregnant 
women 18 years of age or 
older from the C4591001 
study with and without 
evidence of prior 
SARS-CoV-2 infection.
In female participants complying 
with the key protocol criteria 
(evaluable participants):
•
GMR, estimated by the ratio 
of the geometric mean of 
SARS-CoV-2 neutralizing 
titers in pregnant women to 
those in nonpregnant female 
participants 1 month after 
Dose 2
•
SARS-CoV-2 neutralizing titers
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Objectivesa
Estimands
Endpoints
Secondary 
Secondary 
Secondary
To describe the efficacy of 
prophylactic BNT162b2 
against confirmed COVID19
occurring from 7 days after 
Dose 2 through 1 month after 
delivery in maternal
participants 18 years of age 
or older vaccinated at 24 to 
34 weeks’ gestation without 
evidence of prior 
SARS-CoV-2 infection.
In maternal participants 
complying with the key protocol 
criteria (evaluable participants) 
and no serological or virological
evidence (prior to 7 days after 
receipt of Dose 2) of past
SARS-CoV-2 infection:
•
100 × (1 – IRR) [ratio of 
active vaccine to placebo]
•
COVID-19 incidence per 
1000 person-years of blinded 
follow-up based on central laboratory 
or locally confirmed NAAT
To describe the efficacy of 
prophylactic BNT162b2 
against confirmed 
COVID-19 occurring from 
7 days after Dose 2 through 
1 month after delivery in 
maternal participants
18 years of age or older 
vaccinated at 24 to 34 weeks’ 
gestation with and without 
evidence of prior 
SARS-CoV-2 infection.
In maternal participants 
complying with the key protocol 
criteria (evaluable participants):
•
100 × (1 – IRR) [ratio of 
active vaccine to placebo]
•
COVID-19 incidence per 
1000 person-years of blinded follow-
up based on central laboratory or 
locally confirmed NAAT
To describe the efficacy of 
prophylactic BNT162b2 
against asymptomatic
SARS-CoV-2 infection 
through 1 month after 
delivery in maternal 
participants 18 years of age 
or older vaccinated at 24 to 
34 weeks’ gestation without
evidence of prior 
SARS-CoV-2 infection.
In evaluable maternal participants 
without serological or virological
evidence of prior SARS-CoV-2 
infection:
•
100 × (1 – IRR) [ratio of 
active vaccine to placebo]
•
Incidence of asymptomatic infection 
of SARS-CoV-2 based on N-binding 
antibody seroconversion
To describe the immune 
response over time and 
persistence of prophylactic 
BNT162b2 when 
administered to maternal 
participants 18 years of age 
or older vaccinated at 24 to 
34 weeks’ gestation.
In maternal participants 
complying with the key protocol 
criteria (evaluable maternal 
participants) from each vaccine 
group:
•
GMCs/GMTs, at baseline 
(before Dose 1), 2 weeks 
after Dose 2, 1 month after 
Dose 2, at delivery, and 
6 months after delivery
•
GMFRs from baseline 
through 2 weeks after 
Dose 2, 1 month after 
Dose 2, at delivery, and 
6 months after delivery
•
Full-length S-binding IgG levels
•
SARS-CoV-2 neutralizing titers
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Final Protocol Amendment 5, 08 March 2022
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Objectivesa
Estimands
Endpoints
To assess the safety of 
maternal immunization in 
infants born to maternal 
participants 18 years of age 
or older who were vaccinated 
with BNT162b2 during
pregnancy.
In infants born to maternal 
participants receiving at least 
1 dose of study intervention from 
each vaccine group, the
percentage of infants with:
•
Specific birth outcomes
•
AEs from birth through
1 month of age
•
SAEs and AESIs (major 
congenital anomalies, 
developmental delay) 
through 6 months of age
•
Specific birth outcomes
•
AEs from birth through 1 month of 
age
•
SAEs and AESIs (major congenital 
anomalies, developmental delay) 
through 6 months of age
To describe the immune 
response in infants born to 
maternal participants 
vaccinated with prophylactic 
BNT162b2 during 
pregnancy.
In infants born to evaluable 
maternal participants from each 
vaccine group:
•
GMCs and GMFRs, at birth
and 6 months after delivery
•
Full-length S-binding IgG levels
Exploratory
Exploratory
Exploratory
To describe the incidence of 
confirmed COVID-19 among 
maternal participants who
were vaccinated with 
BNT162b2.
In maternal participants who 
received BNT162b2 at initial 
randomization:
•
Incidence per 
1000 person-years of 
follow-up
•
COVID-19 incidence per 
1000 person-years of follow-up 
based on central laboratory or locally 
confirmed NAAT
To describe the incidence of 
asymptomatic SARS-CoV-2 
infection through 6 months 
after delivery in maternal 
participants 18 years of age 
or older vaccinated at 24 to 
34 weeks’ gestation with 
BNT162b2 at initial 
randomization and without
evidence of prior 
SARS-CoV-2 infection.
In maternal participants who 
received BNT162b2 at initial 
randomization and without
evidence of prior SARS-CoV-2 
infection:
•
Incidence per 
1000 person-years of 
follow-up
•
Incidence of asymptomatic 
SARS-CoV-2 infection per 
1000 person-years of follow-up 
based on N-binding antibody 
seroconversion
To describe the serological 
responses among maternal 
participants to the 
BNT162b2 vaccine candidate 
in cases of:
•
Confirmed COVID-19
•
Confirmed severe 
COVID-19
•
SARS-CoV-2 infection 
without confirmed 
COVID-19
In each subset of evaluable 
maternal participants from each 
vaccine group with: 
•
Confirmed COVID-19
•
Confirmed severe 
COVID-19 
•
SARS-CoV-2 infection but 
no confirmed COVID-19
•
GMCs/GMTs and GMFRs at 
baseline, 1 month after 
Dose 2, at delivery, and 
6 months after delivery
•
Full-length S-binding IgG levels
•
SARS-CoV-2 neutralizing titers
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591015
Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
Page 20
Objectivesa
Estimands
Endpoints
To describe the immune 
response to prophylactic 
BNT162b2 between Dose 1 
and Dose 2 when 
administered to maternal 
participants 18 years of age 
or older vaccinated at 27 to 
34 weeks’ gestation in the 
Phase 2 portion of the study.
In evaluable maternal 
participants:
•
GMCs/GMTs at baseline and 
before Dose 2 
•
GMFRs from baseline to 
before Dose 2
•
Full-length S-binding IgG levels
•
SARS-CoV-2 neutralizing titers
To describe the immune 
response in infants born to 
breastfeeding maternal 
participants vaccinated with 
prophylactic BNT162b2
during pregnancy.
In infants born to maternal 
participants from each vaccine 
group, based on the breastfeeding 
status:
•
GMCs and GMFRs, at birth 
and 6 months after delivery
•
Full-length S-binding IgG levels
To describe the safety of 
maternal immunization in 
infants born to breastfeeding 
maternal participants 
vaccinated with prophylactic 
BNT162b2 during
pregnancy.
In infants born to maternal 
participants receiving at least 
1 dose of study intervention from 
each vaccine group, based on the 
breastfeeding status, the 
percentage of infants with:
•
AEs from birth through
1 month of age
•
SAEs and AESIs (major 
congenital anomalies, 
developmental delay) 
through 6 months of age
•
AEs from birth through 1 month of 
age
•
SAEs and AESIs (major congenital 
anomalies, developmental delay) 
through 6 months of age
To describe the incidence of 
confirmed COVID-19 in 
infants born to maternal 
participants who were 
vaccinated with BNT162b2 
during pregnancy.
In infants born to maternal 
participants from each vaccine 
group:
•
Incidence rate of infant 
participants with confirmed 
COVID-19 
•
COVID-19 incidence per 
1000 person-years of follow-up 
based on central laboratory or locally 
confirmed NAAT
To describe MIS-C cases in 
infants born to maternal 
participants who were 
vaccinated with BNT162b2 
during pregnancy.
In infants born to maternal 
participants from each vaccine 
group:
•
Incidence rate of MIS-C 
•
MIS-C incidence per 
1000 person-years of follow-up
a.
HIV-infected participants will not be included in analyses of the objectives, but in separate exploratory 
analyses.  Analyses among HIV-infected women and their infants will be summarized separately.
Overall Design
This will be a global Phase 2/3, randomized, placebo-controlled, observer-blind study 
evaluating the safety, tolerability, and immunogenicity of 30 μg of BNT162b2 or placebo 
administered in 2 doses, 21 days apart, in approximately 350 healthy pregnant women 
18 years of age or older vaccinated at 24 to 34 weeks’ gestation. Participants will be 
randomized 1:1 to receive BNT162b2 or placebo (saline).
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Final Protocol Amendment 5, 08 March 2022
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The Phase 2 portion of the study will include approximately 200 pregnant women
randomized 1:1 to receive BNT162b2 or placebo (saline) at 27 to 34 weeks’ gestation. The 
IRC will review safety data through 7 days after the second dose for all Phase 2 participants.
The Phase 3 portion of this study will assess the safety, tolerability, and immunogenicity of 
BNT162b2 among pregnant women enrolled at 24 to 34 weeks’ gestation. Phase 3 will 
proceed after the first 200 maternal participants have been enrolled in Phase 2.
Maternal participants who originally received placebo will receive BNT162b2 at defined 
time points as part of the study.
Number of Participants
Approximately 200 healthy pregnant women will be enrolled in the Phase 2 portion of the 
study. Approximately 150 healthy pregnant women will be enrolled in the Phase 3 portion.
Intervention Groups and Duration
This study will evaluate a 2-dose (separated by 21 days) schedule of 30 μg of the 
investigational BNT162b2 RNA vaccine candidate (BNT162 RNA-LNP vaccine utilizing 
modRNA and encoding the P2 S) for active immunization against COVID-19.
Healthy pregnant women will be randomized in a 1:1 ratio to receive a 2-dose schedule of 
either:
•
BNT162b2 (BNT162 RNA-LNP vaccine utilizing modRNA and encoding the P2 S) at a 
dose of 30 μg OR
•
Normal saline solution for injection (0.9% NaCl injection).
Each maternal participant will participate in the study for approximately up to 10 months 
depending on the vaccine group to which she was randomized. Her infant will participate in 
the study for approximately 6 months. The study duration will be approximately 14 months.
Data Monitoring Committee or Other Independent Oversight Committee
The study will utilize an IRC, an internal Pfizer committee that will be used during the 
Phase 2 portion of the study to closely monitor safety.
The study will include stopping rules, which may result in a pause to study vaccination 
followed by a review and recommendation by the IRC.
The study will use an external DMC to monitor vaccine safety throughout the study.
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Final Protocol Amendment 5, 08 March 2022
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Statistical Methods
The primary safety objective will be evaluated by descriptive summary statistics for local 
reactions, systemic events, AEs, and SAEs, for each vaccine group.  Descriptive summary 
statistics will include counts and percentages of participants with the indicated endpoint and 
the associated Clopper-Pearson 95% CIs. A 3-tier approach will be used to summarize AEs.
The AEs, including SAEs, reported in the open-label follow-up period will be summarized 
separately from those reported during the blinded follow-up period for maternal participants. 
The safety objective related to infants born to maternal participants, including birth 
outcomes, AEs, SAEs, and AESIs, will be evaluated in a similar way.
There are 2 primary immunogenicity objectives, one for participants without evidence of 
SARS-CoV-2 infection up to 1 month after Dose 2, and the other for participants with and 
without evidence of prior SARS-CoV-2 infection; each will be evaluated by describing 
SARS-CoV-2 neutralizing titers induced by BNT162b2 at 1 month after Dose 2 in maternal 
participants and in a group of randomly selected nonpregnant women within the same age 
group from the C4591001 study. GMRs will be provided along with associated 2-sided 
95% CIs.
Other immunogenicity objectives will be evaluated descriptively by GMTs/GMCs and 
GMFRs of full-length S-binding IgG levels and/or SARS-CoV-2 neutralizing titers and 
associated 2-sided 95% CIs.
The secondary efficacy objectives are to describe VE against the confirmed COVID-19 
illness during the blinded follow-up period, which is defined as VE = 100 × (1 – IRR). IRR 
is calculated as the ratio of first confirmed COVID-19 illness rate in the vaccine group to the 
corresponding illness rate in the placebo group.
VE against asymptomatic infection will be evaluated descriptively, in a similar way.
The incidence rates of confirmed COVID-19 and asymptomatic infection per 
1000 person-years of follow-up in maternal participants after their receipt of BNT162b2 
throughout the study will be provided with the associated 2-sided 95% CIs.
The incidence rate of confirmed COVID-19 and incidence rate of confirmed MIS-C in infant
participants, and associated 2-sided 95% CIs, will also be provided according to the vaccine 
group to which the maternal participants were randomized.
1.2. Schema
Not applicable.
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Final Protocol Amendment 5, 08 March 2022
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1.3. Schedule of Activities 
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.
An unplanned potential COVID-19 illness visit and unplanned potential COVID-19 convalescent visit are required at any time 
between Visit 1 (Vaccination 1) and Visit 8 (6-month postdelivery visit, the final study visit) that potential COVID-19 symptoms are 
reported, including MIS C.
1.3.1. Schedule of Activities for Maternal Participants
Visit Number (Maternal 
Participants)
1
2
3
4
5
6
7
8
Unplanned
Unplanned
Visit Description
Screening:
-28 Days to 
Vaccination
1
Vaccination 
2
2-Week
Post–
Vaccination 
2 Follow-
upa
1-Month 
Post–
Vaccination 
2 
Follow-upa
Delivery
1-Week 
Postdelivery 
Follow-up Call
1-Month 
Postdelivery 
Follow-upb
6-Month 
Postdelivery 
Follow-up
For 
Participants 
Originally 
Randomized 
to Receive 
BNT162b2
Potential 
COVID-19 
Illness Visitc
Potential 
COVID-19 
Convalescent 
Visit
Visit Window (Days)
Day 1
Visit 1
19 to 23
Days After 
Visit 1
11 to 17 
Days After 
Visit 2
28 to 35
Days After 
Visit 2
Varies
7 to 10 Days 
After Delivery
21 to 35 
Days After 
Delivery
160 to 
200 Days 
After 
Delivery
Optimally 
Within 3 
Days After 
Potential 
COVID-19 
Illness 
Onset
28 to 35 
Days After 
Potential 
COVID-19 
Illness Visit
Type of Visit
Clinic
Clinic
Clinic
Clinic
Hospital
Phone Call
Clinic
Clinic
Obtain informed consent
X
Assign single participant identifier 
X
Obtain demography
X
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Final Protocol Amendment 5, 08 March 2022
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Visit Number (Maternal 
Participants)
1
2
3
4
5
6
7
8
Unplanned
Unplanned
Visit Description
Screening:
-28 Days to 
Vaccination
1
Vaccination 
2
2-Week
Post–
Vaccination 
2 Follow-
upa
1-Month 
Post–
Vaccination 
2 
Follow-upa
Delivery
1-Week 
Postdelivery 
Follow-up Call
1-Month 
Postdelivery 
Follow-upb
6-Month 
Postdelivery 
Follow-up
For 
Participants 
Originally 
Randomized 
to Receive 
BNT162b2
Potential 
COVID-19 
Illness Visitc
Potential 
COVID-19 
Convalescent 
Visit
Visit Window (Days)
Day 1
Visit 1
19 to 23
Days After 
Visit 1
11 to 17 
Days After 
Visit 2
28 to 35
Days After 
Visit 2
Varies
7 to 10 Days 
After Delivery
21 to 35 
Days After 
Delivery
160 to 
200 Days 
After 
Delivery
Optimally 
Within 3 
Days After 
Potential 
COVID-19 
Illness 
Onset
28 to 35 
Days After 
Potential 
COVID-19 
Illness Visit
Type of Visit
Clinic
Clinic
Clinic
Clinic
Hospital
Phone Call
Clinic
Clinic
Record current alcohol and tobacco 
usage
X
Obtain medical history, including 
obstetric and gestational history
X
Phase 3 only: For participants who 
are HIV-positive, record latest
CD4 count and HIV viral load
X
X
X
X
X
X
Record LMP and EDD
X
Measure vital signs
X
X
X
Perform physical examination
X
Perform targeted physical 
examination
X
X
Perform obstetric examination
X
X
X
Perform obstetric ultrasound
X
Record nonstudy vaccine information
X
X
X
X
X
X
X
X
Record concomitant medication 
associated with an adverse event or 
serious adverse event
X
X
X
X
X
X
X
Xd
Record prohibited medications
X
X
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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
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Final Protocol Amendment 5, 08 March 2022
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Visit Number (Maternal 
Participants)
1
2
3
4
5
6
7
8
Unplanned
Unplanned
Visit Description
Screening:
-28 Days to 
Vaccination
1
Vaccination 
2
2-Week
Post–
Vaccination 
2 Follow-
upa
1-Month 
Post–
Vaccination 
2 
Follow-upa
Delivery
1-Week 
Postdelivery 
Follow-up Call
1-Month 
Postdelivery 
Follow-upb
6-Month 
Postdelivery 
Follow-up
For 
Participants 
Originally 
Randomized 
to Receive 
BNT162b2
Potential 
COVID-19 
Illness Visitc
Potential 
COVID-19 
Convalescent 
Visit
Visit Window (Days)
Day 1
Visit 1
19 to 23
Days After 
Visit 1
11 to 17 
Days After 
Visit 2
28 to 35
Days After 
Visit 2
Varies
7 to 10 Days 
After Delivery
21 to 35 
Days After 
Delivery
160 to 
200 Days 
After 
Delivery
Optimally 
Within 3 
Days After 
Potential 
COVID-19 
Illness 
Onset
28 to 35 
Days After 
Potential 
COVID-19 
Illness Visit
Type of Visit
Clinic
Clinic
Clinic
Clinic
Hospital
Phone Call
Clinic
Clinic
Review eligibility criteria
X
X
Review temporary delay criteria
X
X
Review continued eligibility
X
X
X
X
X
X
Explain/review participant 
communication methods (including 
for e-diary completion), assist the 
participant with downloading the 
app, or issue provisioned device, if 
required
X
Record systemic events at baseline in 
the e-diary
X
Assign participant randomization and 
container number
X
Collect blood sample for 
immunogenicity assessment (~20 mL 
per blood sample) 
X
Xe
X
X
X
X
X
Obtain nasal (midturbinate swab)
X
X
Xd
Administer study intervention
X
X
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Final Protocol Amendment 5, 08 March 2022
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Visit Number (Maternal 
Participants)
1
2
3
4
5
6
7
8
Unplanned
Unplanned
Visit Description
Screening:
-28 Days to 
Vaccination
1
Vaccination 
2
2-Week
Post–
Vaccination 
2 Follow-
upa
1-Month 
Post–
Vaccination 
2 
Follow-upa
Delivery
1-Week 
Postdelivery 
Follow-up Call
1-Month 
Postdelivery 
Follow-upb
6-Month 
Postdelivery 
Follow-up
For 
Participants 
Originally 
Randomized 
to Receive 
BNT162b2
Potential 
COVID-19 
Illness Visitc
Potential 
COVID-19 
Convalescent 
Visit
Visit Window (Days)
Day 1
Visit 1
19 to 23
Days After 
Visit 1
11 to 17 
Days After 
Visit 2
28 to 35
Days After 
Visit 2
Varies
7 to 10 Days 
After Delivery
21 to 35 
Days After 
Delivery
160 to 
200 Days 
After 
Delivery
Optimally 
Within 3 
Days After 
Potential 
COVID-19 
Illness 
Onset
28 to 35 
Days After 
Potential 
COVID-19 
Illness Visit
Type of Visit
Clinic
Clinic
Clinic
Clinic
Hospital
Phone Call
Clinic
Clinic
Assess acute reactions for at least 
30 minutes after study intervention 
administration
X
X
Provide/ensure participant has a 
thermometer and measuring device
X
X
Review reactogenicity e-diary data 
(daily review is optimal during the 
active diary period of 7 days 
following study intervention 
administration)
Review ongoing reactogenicity 
e-diary symptoms with participant 
and obtain stop dates
X
X
Record pregnancy outcome 
information
X
X
Record AEs and SAEs as 
appropriatef
X
X
X
X
Xd
X
Xd
Xd
Xd
Xd
Collect e-diary or assist the 
participant to delete application
X
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Final Protocol Amendment 5, 08 March 2022
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Visit Number (Maternal 
Participants)
1
2
3
4
5
6
7
8
Unplanned
Unplanned
Visit Description
Screening:
-28 Days to 
Vaccination
1
Vaccination 
2
2-Week
Post–
Vaccination 
2 Follow-
upa
1-Month 
Post–
Vaccination 
2 
Follow-upa
Delivery
1-Week 
Postdelivery 
Follow-up Call
1-Month 
Postdelivery 
Follow-upb
6-Month 
Postdelivery 
Follow-up
For 
Participants 
Originally 
Randomized 
to Receive 
BNT162b2
Potential 
COVID-19 
Illness Visitc
Potential 
COVID-19 
Convalescent 
Visit
Visit Window (Days)
Day 1
Visit 1
19 to 23
Days After 
Visit 1
11 to 17 
Days After 
Visit 2
28 to 35
Days After 
Visit 2
Varies
7 to 10 Days 
After Delivery
21 to 35 
Days After 
Delivery
160 to 
200 Days 
After 
Delivery
Optimally 
Within 3 
Days After 
Potential 
COVID-19 
Illness 
Onset
28 to 35 
Days After 
Potential 
COVID-19 
Illness Visit
Type of Visit
Clinic
Clinic
Clinic
Clinic
Hospital
Phone Call
Clinic
Clinic
Collection of COVID-19–related 
clinical and laboratory information 
(including local diagnosis)
X
X
Abbreviations: EDD = estimated delivery date; HIV = human immunodeficiency virus; LMP = last menstrual period.
a.
The 2-week postvaccination follow-up and 1-month postvaccination follow-up visits will not be performed if delivery occurs before the visits. If delivery 
occurs before Vaccination 2, the second dose should be given as soon as possible after delivery. Once delivery occurs, the visit windows are calculated 
based on the delivery date.
b.
All maternal participants will be unblinded. Placebo recipients will be given BNT162b2 and move to follow the procedures in Section 1.3.2.
c.
The COVID-19 illness visit may be conducted as an in-person or telehealth visit.
d.
Only AEs occurring up to 48 hours after each blood draw and nasal midturbinate swab collection must be recorded.
e.
Prevaccination blood samples for immunogenicity will be drawn from maternal participants in Phase 2 only.
f.
The investigator and site staff will ensure the active elicitation and collection of AEs and SAEs through 1 month after Vaccination 2.  From 1 month after 
Vaccination 2 until the 6-month postdelivery follow-up, SAEs will be collected.
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1.3.2. Schedule of Activities for Maternal Participants Who Were Originally Assigned to Placebo
Visit Number (Maternal Participants)
101
102
103
Visit Description
1-Month Postdelivery Follow-up
Vaccination 3
Vaccination 4
1-Month
Telephone Contact 
Follow-up
Visit Window (Days)
21 to 35 Days After Delivery
19 to 23 Days After Visit 
101
28 to 35 Days After Visit 
102
Type of Visit
Clinic
Clinic
Phone Call
Confirm the participant originally received only placebo at 
Vaccination 1/2.  Secondary confirmation by another site staff member 
is required
X
Collect prohibited medication use
X
X
X
For participants who are HIV-positive, record latest
CD4 count and HIV viral load
X
Review and consider eligibility
X
X
Review temporary delay criteria
X
X
Collect blood sample for immunogenicity assessment
~20 mL
Obtain nasal (midturbinate) swab
X
X
Obtain vaccine vial allocation via IRT
X
X
Administer BNT162b2
X
X
Assess acute reactions for at least 30 minutes after study intervention 
administration
X
X
Collect AEs and SAEs as appropriate
X
X
X
Contact the participant by telephone
X
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1.3.3. Schedule of Activities for Infant Participants
Visit Number (Infant Participants)
1
2
3
Unplanned
Unplanned
Visit Description
Delivery
1-Week 
Postdelivery 
Follow-up
6-Months-of-Age 
Follow-up
Potential 
COVID-19 
Illness Visit
Potential 
COVID-19 
Convalescent 
Visit
Visit Window (Days)
Varies
7 to 10 Days After 
Delivery
160 to 200 Days 
After Delivery
Optimally 
Within 3 Days 
After Potential 
COVID-19 
Illness Onset
28 to 35 Days 
After Potential 
COVID-19 
Illness Visit
Type of Visit
Hospital
Phone Call
Clinic
Assign single participant identifier
X
Record demography and available birth information 
X
Measure vital signs
X
Perform physical examination
X
Record concomitant medication associated with an adverse event/serious 
adverse event
X
X
X
Review eligibility
X
Review continued eligibility
X
X
Record breastfeeding information
X
X
Collect blood sample for immunogenicity assessment (up to ~5 mL per 
blood sample depending on weight)
X
X
Cord blood sample (~10 mL) for immunogenicity assessment
Xa
Record adverse events
X
Xb
Xb
X
X
Record serious adverse events and adverse events of special interest
X
X
X
X
X
Collect prohibited medication use
X
X
Obtain nasal swab
X
Collection of COVID-19–related clinical and laboratory information 
(including local diagnosis)
X
X
Collect e-diary or assist the maternal participant to delete application
X
Abbreviations: HIV = human immunodeficiency virus; IRT = interactive response technology.
a.
If cord blood is unavailable, a blood sample may be collected from the infant participant up to 72 hours after birth but preferably within 24 hours after birth.
b.
Active AE collection through 1 month of age.
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2. INTRODUCTION
The BNT162b2 RNA-based COVID-19 vaccine is currently being investigated for 
prevention of COVID-19 in healthy pregnant women.
2.1. Study Rationale
The purpose of the study is to describe the safety, tolerability, and immunogenicity of 
BNT162b2 RNA-based COVID-19 vaccine against COVID-19 in healthy pregnant women.  
There are currently no licensed vaccines to prevent infection with SARS-CoV-2 or 
COVID-19.  Pregnant women are at risk of acquiring SARS-CoV-2 infection, developing 
COVID-19 and COVID-19–associated complications. Given the global crisis of COVID-19 
and fast expansion of the disease globally, the rapid development of an effective vaccine for 
use in this population is of utmost importance.
2.2. Background
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China.  
In January 2020, it became clear that a novel coronavirus (2019-nCoV) was the underlying 
cause.  Later in January, the genetic sequence of the 2019-nCoV became available to the 
WHO and public (MN908947.3), and the virus was categorized in the Betacoronavirus
subfamily.  By sequence analysis, the phylogenetic tree revealed a closer relationship to 
SARS virus isolates than to another coronavirus infecting humans, the MERS virus.1,2
SARS-CoV-2 infections and the resulting disease, COVID-19, have spread globally, 
affecting a growing number of countries, and on 11 March 2020, the WHO characterized the 
COVID-19 outbreak as a pandemic.3  On 16 December 2020, The Center for Systems 
Science and Engineering at Johns Hopkins University reported more than 73 million cases 
globally, with over 1.6 million deaths from 191 countries. Global case rates and deaths have 
continued to increase, with the United States reporting the most cases and deaths of any other 
country.  There are currently no vaccines broadly available to prevent SARS-CoV-2 
infections or the disease it causes, COVID-19.4
Pregnant women are at risk for acquiring SARS-CoV-2 infection and COVID-19.5,6,7
Pregnancy may confer increased risk of severe COVID-19 because of physiological changes 
during pregnancy that can increase susceptibility to respiratory infections and subsequent 
rapid progression to respiratory failure.8 Additionally, pregnant women with COVID-19 
have been reported to have higher rates of preterm birth, cesarean delivery, fetal distress, and 
infants requiring neonatal intensive care.8,9,10,11 While COVID-19 in children is reported less 
commonly than in adults, infants <1 year of age, if infected with SARS-CoV-2, may be at
increased risk of severe disease, and younger age groups have increasing rates of 
COVID-19–associated hospitalization.12,13 Prevention of SARS-CoV-2 infection and 
COVID-19 is critically important in pregnant women, and maternal immunization may 
confer some protection to their infants.
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Given the rapid transmission of COVID-19 and incidence of disease in the United States and 
elsewhere, the rapid development of an effective vaccine is of utmost importance.
A prophylactic, RNA-based SARS-CoV-2 vaccine provides one of the most flexible and 
fastest approaches available to immunize against the emerging virus.14,15 The development 
of an RNA-based vaccine encoding a viral antigen, which is then expressed by the vaccine 
recipient as a protein capable of eliciting protective immune responses, provides significant 
advantages over more traditional vaccine approaches.  Unlike live attenuated vaccines, RNA 
vaccines do not carry the risks associated with infection and may be given to people who 
cannot be administered live virus (eg, pregnant women and immunocompromised persons).  
RNA-based vaccines are manufactured via a cell-free in vitro transcription process, which 
allows an easy and rapid production and the prospect of producing high numbers of 
vaccination doses within a shorter time period than achieved with traditional vaccine 
approaches.  This capability is pivotal to enable the most effective response in outbreak 
scenarios.14,15
There are no ongoing randomized controlled COVID-19 vaccine studies including pregnant
women. Vaccination of pregnant women has been used globally to protect both women and 
their infants against influenza and as a mechanism to protect infants against pertussis.
Several studies have demonstrated that maternal immunization is safe for both mother and 
infant and an important strategy to protect pregnant women and their infants against 
infectious diseases.  Currently maternal immunization studies are being conducted as part of 
the development of novel RSV and GBS vaccines.16,17
BNT162b2 is a SARS-CoV-2–RNA-LNP vaccine based on a platform of modRNA with 
blunted innate immune sensor–activating capacity and augmented expression encoding the 
P2 S.
This study will describe the safety of BNT162b2 in pregnant women and their infants. It will 
also assess the immunogenicity of BNT162b2 in pregnant women, the transfer of antibody to 
their infants, and the kinetics of antibody transfer in the infant.
2.2.1. Clinical Overview
Prior to this study, clinical data from BNT162b2 established a favorable safety profile 
characterized by mild, localized, and transient effects. Study C4591001 (NCT04368728) is 
an ongoing Phase 1/2/3 trial in ~46,000 participants designed to generate safety, tolerability, 
immunogenicity, and efficacy data from a novel RNA-based vaccine candidate.18  The trial is 
being conducted in a heterogeneous study population: eligible healthy participants ≥12 years 
of age, including those participants with stable chronic medical conditions, including HIV-, 
HCV-, and HBV-positive participants.  The study consists of 2 parts: Phase 1: to identify the 
preferred vaccine candidate (BNT162b1 or BNT162b2) and dose level (10 μg, 20 μg, 30 μg, 
or 100 μg [for BNT162b1]); Phase 2/3: an expanded-cohort and efficacy part for the selected 
vaccine candidate (BNT162b2).
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The available immunogenicity data from Phase 1 participants show that BNT162b2 induced 
a robust IgG-binding response to S1 and a SARS-CoV-2–neutralizing response.  
Immunogenicity substantially increased following the second dose of vaccine.  BNT162b2 
induces a strong antigen-specific Th1-skewed CD4+ response and a strong antigen-specific 
CD8+ response.  BNT162b2 was selected from the Phase 1 part of the study based on the
overall safety, tolerability, and immunogenicity.  In a mid-November 2020 analysis of 
36,621 participants randomized 1:1 to vaccine or placebo, who were included in the 
per-protocol efficacy analysis population of participants without evidence of SARS-CoV-2 
infection prior to 7 days after completion of the vaccination schedule, the efficacy in 
preventing confirmed COVID-19 occurring at least 7 days after the second dose of vaccine 
was 95.0%, with 8 COVID-19 cases in the active vaccine group and 162 COVID-19 cases in 
the placebo group.  Subgroup analyses of the primary efficacy endpoint showed similar 
efficacy point estimates across age groups, sexes, racial and ethnic groups, and participants 
with medical comorbidities associated with high risk of severe COVID-19.  Secondary 
efficacy analyses suggested benefit of the vaccine in preventing severe COVID-19, in 
preventing COVID-19 following the first dose, and in preventing COVID-19 in individuals 
with prior SARS-CoV-2 infection, although available data for these outcomes did not allow 
for firm conclusions.19
In a subsequent analysis of 927 confirmed symptomatic cases of COVID-19, an efficacy rate 
of 91.3% was observed for BNT162b2 in preventing such cases occurring between 7 days to 
6 months after the second dose.20 Furthermore, from the same analysis, BNT162b2 was 
shown to have an efficacy of:
•
100% in preventing severe disease as defined by the CDC.
•
95.3% in preventing severe disease as defined by the FDA.
•
100% in preventing COVID-19 cases in South Africa, where the B.1.351 lineage is 
prevalent.
Safety data from approximately 38,000 participants at least 16 years of age randomized 1:1
to vaccine or placebo with a median of 2 months of follow-up after the second dose 
demonstrated a favorable safety profile.  Available safety data from all participants enrolled 
through the 14 November 2020 data cutoff (N = 43,252, which includes late enrollment of 
additional adolescent and adult participants) were consistent with the safety profile for the 
approximately 38,000 participants with a median follow-up of 2 months and also did not 
raise specific safety concerns.19
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The most common solicited adverse reactions were injection site reactions (84.1%), 
fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), 
and fever (14.2%); severe adverse reactions occurred in 0.0% to 4.6% of participants, were 
more frequent after Dose 2 than after Dose 1, and were generally less frequent in 
participants ≥55 years of age (≤2.8%) as compared to younger participants (≤4.6%).  The 
frequency of SAEs was low (<0.5%), without meaningful imbalances between study arms. 
Lymphadenopathy was observed in 0.3% of vaccine recipients as compared to <0.1% of 
those who received placebo.  Otherwise, there were no notable patterns or numerical 
imbalances between vaccine groups for specific categories of nonserious AEs (including 
other neurologic, neuroinflammatory, and thrombotic events) that would suggest a causal 
relationship to BNT162b2.  With the exception of more frequent, generally mild to moderate 
reactogenicity in participants <55 years of age, the safety profile of BNT162b2 was generally 
similar across age groups, sexes, ethnic and racial groups, participants with or without 
medical comorbidities, and participants with or without evidence of prior SARS-CoV-2 
infection at enrollment.19
Numerous COVID-19 vaccines are currently in development globally, and several candidate 
COVID-19 vaccines (eg, mRNA vaccines and adenovirus-vectored vaccines expressing the 
S protein) have been shown to be efficacious in the prevention of COVID-19 in clinical 
studies and are now available under temporary or emergency authorizations.21 BNT162b2, 
an RNA-based COVID-19 vaccine given as a 2-dose series administered 21 days apart, was 
shown to be safe and effective in a Phase 1/2/3 study and has received authorizations for 
temporary or emergency use or marketing authorizations in multiple countries and has been 
fully licensed for use in individuals 16 years of age and above in the US as of
23 August 2021.22,23
On 22 September 2021, based on safety and immunogenicity data from approximately 
300 immunocompetent adult booster-dose recipients from Study C4591001, the FDA issued 
the EUA for a single booster dose of BNT162b2 30 μg for 1) individuals 65 years of age and 
older; 2) individuals 18 through 64 years of age at high risk of severe COVID-19; and 
3) individuals 18 through 64 years of age whose frequent institutional or occupational 
exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19, 
including severe COVID-19.24  On 19 November 2021, the FDA amended the EUA, 
authorizing use of a single booster dose for all individuals 18 years of age and older after 
completion of primary vaccination with an FDA-approved COVID-19 vaccine.25 On 
09 December 2021, the FDA again amended the EUA to authorize the use of a single booster 
dose for administration to individuals 16 and 17 years of age at least 6 months after 
completion of primary vaccination with BNT162b2.26  In addition, a booster dose of the 
vaccine is authorized in the EU and other countries, with recommendations for populations 
varying based on local health authority guidance.27,28
The currently available safety and immunogenicity data are presented in the BNT162 IB.
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2.3. Benefit/Risk Assessment
There is an ongoing global pandemic of COVID-19, however, numerous COVID-19 
vaccines are currently in development globally, and several candidate COVID-19 vaccines 
(eg, mRNA vaccines and adenovirus-vectored vaccines expressing the S protein) have been 
shown to be efficacious in the prevention of COVID-19 in clinical studies and are now 
available under temporary or emergency authorizations or have licenses or conditional 
marketing authorizations. While there were no data available from clinical trials on the use 
of BNT162 vaccines in pregnant women, preliminary data are available from the ongoing
Phase 1/2/3 clinical trial evaluating the use of BNT162b2 30-μg doses administered 21 days 
apart in nonpregnant adults.
In the C4591001 study, BNT162b2 has been shown to elicit increased local and systemic 
adverse reactions as compared to those in the placebo arm, usually lasting a few days.  
The most common solicited adverse reactions were injection site reactions (84.1%), 
fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), 
and fever (14.2%).19 Adverse reactions characterized as reactogenicity were generally mild 
to moderate.  The number of participants reporting hypersensitivity-related AEs was 
numerically higher in the vaccine group compared with the placebo group (137 [0.63%] vs 
111 [0.51%]).  Severe adverse reactions occurred in 0.0% to 4.6% of participants, were more 
frequent after Dose 2 than after Dose 1, and were generally less frequent in older adults 
(>55 years of age) (≤2.8%) as compared to younger participants (≤4.6%).  Among reported 
unsolicited AEs, lymphadenopathy occurred much more frequently in the active vaccine 
group than the placebo group and is plausibly related to vaccination.  SAEs, while 
uncommon (<1.0%), represented medical events that occur in the general population at 
similar frequency as observed in the study.19
No specific safety concerns were identified in subgroup analyses by age, race, ethnicity, 
medical comorbidities, or prior SARS-CoV-2 infection.  The risks are based on the observed 
safety profile to date, which shows mostly mild reactogenicity, low incidence of severe or 
serious events, and no clinically concerning safety observations.  The preponderance of 
severe cases of COVID-19 in the placebo group relative to the BNT162b2 group (9 of 10) 
suggests no evidence of VAED.19
In the latest analysis from C4591001, vaccine safety has been evaluated in more than 
44,000 participants ≥16 years of age, with more than 12,000 vaccinated participants having at 
least 6 months follow-up after their second dose.  No serious safety concerns have been 
observed in this timeframe.  Side effects observed in this analysis were generally consistent 
with previously reported results.20
Continued clinical investigation is justified, given:
•
the threat posed by the increasing number of globally distributed outbreaks of 
SARS-CoV-2 infection.
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•
the potential of the BioNTech platform of RNA-based vaccines to deliver high numbers 
of vaccine doses rapidly in a single production campaign.
•
the threat posed by the SARS-CoV-2 variants emerging worldwide.
•
the potential need for enhancing immunoresponses to overcome waning immunity.
These data suggest a favorable risk/benefit profile in pregnant women.  Anticipated AEs after 
vaccination in maternal participants are expected to be manageable using routine 
symptom-driven standard of care as determined by the investigators. As a result, the profile 
of these vaccine candidates supported initiation of this PASS clinical study. This 
interventional study is designated as a PASS, identified as Category 3 in the EU RMP, and is 
conducted as a conditional marketing approval commitment to the EMA and Swissmedic and 
an emergency use authorization commitment to the US FDA and numerous other health 
authorities under respective national emergency use legislation.
DART studies have been completed. In summary, administration of BNT162b2 to female 
rats twice before the start of mating and twice during gestation at the human clinical dose 
was associated with nonadverse effects (body weight, food consumption, and effects 
localized to the injection site) after each dose administration. However, there were no effects 
of BNT162b2 administration on mating performance, fertility, or any ovarian or uterine 
parameters in the female rats or on embryo-fetal or postnatal survival, growth, or 
development in the offspring. An immune response was confirmed in female rats following 
administration of each vaccine candidate and these responses were also detectable in the 
offspring (fetuses and pups). Additional details are included in the IB.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of BNT162b2 may be found in the IB, which is the SRSD for this study.
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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention: BNT162 RNA-Based COVID-19 Vaccine
Potential for local reactions (injection site redness,  
injection site swelling, and injection site pain) and 
systemic events (fever, fatigue, headache, chills, 
vomiting, diarrhea, muscle pain, and joint pain) 
following vaccination.
These are common adverse reactions seen with 
other vaccines, as noted in the FDA CBER 
guidelines on toxicity grading scales for healthy 
adult volunteers enrolled in preventive vaccine 
clinical trials.29
•
Phase 1 data from the C4591001 study 
demonstrated that the 30-μg dose had a 
tolerable reactogenicity profile.30
•
This study employs the use of a reactogenicity 
e-diary to monitor local reactions and systemic 
events in real time.
•
All participants will be observed for at least 
30 minutes after vaccination.
•
In addition, the study will enroll a smaller 
subset of pregnant women in Phase 2 (N=200) 
and have a review of 7-day safety data by an 
IRC.
Unknown AEs with a novel vaccine.
There are limited data available because of the 
ongoing C4591001 study (Phase 1 completed, 
Phase 2/3 ongoing). To date, the safety and 
tolerability profile of BNT162b2 is consistent
with what has been expected from nonclinical 
studies and clinical studies in other RNA-based 
compounds.31,32
•
An IRC (in Phase 2) will review safety. 
Stopping rules will be in place for Phase 2,
which may result in a pause to study 
vaccination followed by a review and
recommendation by the IRC.
•
A DMC will be used throughout the study to 
review all safety data.
•
All participants will be observed for at least 
30 minutes after vaccination.
•
AE and SAE reports will be collected from the 
signing of the ICD through 1 month after the 
second dose of vaccine.
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
•
In maternal participants who receive 
BNT162b2 1 month after delivery, AEs will be 
collected from the signing of the ICD to 
1 month after Vaccination 4 (Visit 103) for 
those maternal participants who originally 
received placebo and go on to receive 
BNT162b2.
Potential for COVID-19 enhancement.
Disease enhancement has been seen following 
vaccination with RSV, feline coronavirus, and 
Dengue virus vaccines.
•
Eligibility criteria will exclude any pregnant 
participants who have had a previous clinical 
(signs/symptoms only) or microbiological 
(signs/symptoms and positive SARS-CoV-2 
NAAT result) diagnosis of COVID-19.
•
Monitoring for cases of COVID-19 developing 
during the study will be reported.
Potential for adverse obstetric and/or neonatal 
outcomes following vaccination.
There are no ongoing COVID-19 vaccine studies 
including pregnant women and, therefore, the 
potential for adverse obstetric and/or neonatal 
outcomes following vaccination while pregnant is 
unknown.
•
Stopping rules for obstetric and neonatal AEs 
occurring after study vaccination and/or 
possibly deemed related to study vaccination in 
the Phase 2 portion of the trial. If a stopping 
rule is triggered, a pause of study vaccination
will be put in place until there is a review of all 
relevant safety events and evaluation by the 
IRC.
Very rare cases of anaphylaxis, myocarditis, and 
pericarditis have been reported after authorization in 
recipients of BNT162b2.
Anaphylaxis: The estimated rate is 5.0 per million 
doses administered.
Myocarditis and pericarditis: Very rare cases 
of myocarditis and pericarditis have been 
reported following vaccination with mRNA 
COVID-19 vaccines. Typically, the cases 
have occurred more often in younger men and 
after the second dose of the vaccine and within 
14 days after vaccination. These are generally 
mild cases, and individuals tend to recover within 
a short time following standard treatment and rest.  
•
Specific reference to these risks is made within 
the ICD, with instruction to contact a 
healthcare professional if a case is suspected.
•
For anaphylaxis, there is an on-site 30-minute 
observation period after vaccination.
•
Instructions for handling suspected cases of 
myocarditis and pericarditis are found in 
Section 8.1.4.
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Healthcare professionals should be alert to the 
signs and symptoms of myocarditis and 
pericarditis in vaccine recipients.
Study Procedures
Participants will be required to attend healthcare 
facilities during the global SARS-CoV-2 pandemic.
Without appropriate social distancing and PPE, 
there is a potential for increased exposure to 
SARS-CoV-2.
•
Pfizer will work with sites to ensure an 
appropriate COVID-19 prevention strategy.
•
Potential COVID-19 illness visits can be 
conducted via telehealth, without the need for 
an in-person visit, if required, with the 
maternal participant performing a self-swab or 
obtaining a swab from her infant.
Venipuncture will be performed during the study.
There is the risk of bleeding, bruising, hematoma 
formation, and infection at the venipuncture site.
•
Only appropriately qualified personnel will
obtain the blood draw.
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2.3.2. Benefit Assessment
Benefits to individual maternal participants may include:
•
Receipt of a potentially efficacious COVID-19 vaccine during a global pandemic.
•
Access to COVID-19 diagnostic and antibody testing.
•
Contributing to research to help others in a time of global pandemic.
•
Potential antibody protection for infants born to mothers who were vaccinated with 
COVID-19 vaccine.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks identified in association with BNT162 RNA-based COVID-19 
vaccine are justified by the anticipated benefits that may be afforded to healthy participants.
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectivesa
Estimands
Endpoints
Primary Safety
Primary Safety
Primary Safety
To describe the safety and 
tolerability of prophylactic 
BNT162b2 when administered to 
maternal participants 18 years of 
age or older vaccinated at 24 to 
34 weeks’ gestation.
In maternal participants 
receiving at least 1 dose of 
study intervention from each 
vaccine group, the percentage of 
maternal participants reporting:
•
Local reactions for up to 
7 days following each dose
•
Systemic events for up to 
7 days following each dose
•
AEs from Dose 1 through
1 month after Dose 2
•
SAEs from Dose 1 through
1 month after delivery
•
Prompted local reactions 
(redness, swelling, and pain at 
the injection site)
•
Prompted systemic events 
(fever, fatigue, headache, chills, 
vomiting, diarrhea, new or 
worsened muscle pain, and new 
or worsened joint pain)
•
AEs
•
SAEs
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Objectivesa
Estimands
Endpoints
Primary Immunogenicity
Primary Immunogenicity 
Primary Immunogenicity
To describe the immune response 
to prophylactic BNT162b2 in
maternal participants 18 years of 
age or older vaccinated at 24 to 
34 weeks’ gestation and reference 
to the immune response in 
nonpregnant women 18 years of 
age or older from the C4591001 
study without evidence of past 
SARS-CoV-2 infection.
In female participants 
complying with the key 
protocol criteria (evaluable 
participants) and no serological 
or virological evidence (up to 
1 month after receipt of the 
second dose) of past 
SARS-CoV-2 infection:
•
GMR, estimated by the 
ratio of the geometric mean 
of SARS-CoV-2 
neutralizing titers in 
pregnant women to those in 
nonpregnant women
1 month after Dose 2
•
SARS-CoV-2 neutralizing titers
To describe the immune response 
to prophylactic BNT162b2 in
maternal participants 18 years of 
age or older vaccinated at 24 to 
34 weeks’ gestation and reference 
to the immune response in 
nonpregnant women 18 years of 
age or older from the C4591001 
study with and without evidence of 
prior SARS-CoV-2 infection.
In female participants 
complying with the key 
protocol criteria (evaluable 
participants):
•
GMR, estimated by the 
ratio of the geometric mean 
of SARS-CoV-2 
neutralizing titers in 
pregnant women to those in 
nonpregnant female 
participants 1 month after 
Dose 2
•
SARS-CoV-2 neutralizing titers
Secondary 
Secondary
Secondary 
To describe the efficacy of 
prophylactic BNT162b2 against 
confirmed COVID-19 occurring 
from 7 days after Dose 2 through 
1 month after delivery in maternal 
participants 18 years of age or 
older vaccinated at 24 to 
34 weeks’ gestation without 
evidence of prior SARS-CoV-2 
infection.
In maternal participants 
complying with the key 
protocol criteria (evaluable 
participants) and no serological 
or virological evidence (prior to 
7 days after receipt of Dose 2) 
of past SARS-CoV-2 infection:
•
100 × (1 – IRR) [ratio of 
active vaccine to placebo]
•
COVID-19 incidence per 
1000 person-years of blinded
follow-up based on central 
laboratory or locally confirmed 
NAAT 
To describe the efficacy of 
prophylactic BNT162b2 against 
confirmed COVID-19 occurring 
from 7 days after Dose 2 through 
1 month after delivery in maternal 
participants 18 years of age or 
older vaccinated at 24 to 34 
weeks’ gestation with and without 
evidence of prior SARS-CoV-2 
infection.
In maternal participants 
complying with the key 
protocol criteria (evaluable 
participants):
•
100 × (1 – IRR) [ratio of 
active vaccine to placebo]
•
COVID-19 incidence per 
1000 person-years of blinded 
follow-up based on central 
laboratory or locally confirmed 
NAAT
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Objectivesa
Estimands
Endpoints
To describe the efficacy of 
prophylactic BNT162b2 against 
asymptomatic SARS-CoV-2 
infection through 1 month after 
delivery in maternal participants 
18 years of age or older vaccinated 
at 24 to 34 weeks’ gestation
without evidence of prior 
SARS-CoV-2 infection.
In evaluable maternal 
participants without serological 
or virological evidence of prior 
SARS-CoV-2 infection:
•
100 × (1 – IRR) [ratio of 
active vaccine to placebo]
•
Incidence of asymptomatic 
infection of SARS-CoV-2 based 
on N-binding antibody
seroconversion
To describe the immune response 
over time and persistence of 
prophylactic BNT162b2 when 
administered to maternal 
participants 18 years of age or 
older vaccinated at 24 to 
34 weeks’ gestation.
In maternal participants 
complying with the key 
protocol criteria (evaluable 
maternal participants) from each 
vaccine group:
•
GMCs/GMTs, at baseline 
(before Dose 1), 2 weeks 
after Dose 2, 1 month after 
Dose 2, at delivery, and 
6 months after delivery
•
GMFRs from baseline 
through 2 weeks after 
Dose 2, 1 month after 
Dose 2, at delivery, and 
6 months after delivery
•
Full-length S-binding IgG levels
•
SARS-CoV-2 neutralizing titers
To assess the safety of maternal 
immunization in infants born to 
maternal participants 18 years of 
age or older who were vaccinated 
with BNT162b2 during pregnancy.
In infants born to maternal 
participants receiving at least 
1 dose of study intervention 
from each vaccine group, the 
percentage of infants with:
•
Specific birth outcomes
•
AEs from birth through
1 month of age
•
SAEs and AESIs (major 
congenital anomalies, 
developmental delay) 
through 6 months of age
•
Specific birth outcomes
•
AEs from birth through 1 month 
of age
•
SAEs and AESIs (major 
congenital anomalies, 
developmental delay) through 
6 months of age
To describe the immune response 
in infants born to maternal 
participants vaccinated with 
prophylactic BNT162b2 during 
pregnancy.
In infants born to evaluable 
maternal participants from each 
vaccine group:
•
GMCs and GMFRs, at birth
and 6 months after delivery
•
Full-length S-binding IgG levels
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Objectivesa
Estimands
Endpoints
Exploratory
Exploratory
Exploratory
To describe the incidence of 
confirmed COVID-19 among 
maternal participants who were 
vaccinated with BNT162b2.
In maternal participants who 
received BNT162b2 at initial 
randomization:
•
Incidence per 
1000 person-years of 
follow-up
•
COVID-19 incidence per 
1000 person-years of follow-up 
based on central laboratory or 
locally confirmed NAAT
To describe the incidence of 
asymptomatic SARS-CoV-2 
infection through 6 months after 
delivery in maternal participants
18 years of age or older vaccinated 
at 24 to 34 weeks’ gestation with 
BNT162b2 at initial randomization 
and without evidence of prior 
SARS-CoV-2 infection.
In maternal participants who 
received BNT162b2 at initial 
randomization and without 
evidence of prior SARS-CoV-2 
infection:
•
Incidence per 1000 
person-years of follow-up
•
Incidence of asymptomatic 
SARS-CoV-2 infection per 1000 
person-years of follow-up based 
on N-binding antibody 
seroconversion
To describe the serological 
responses among maternal 
participants to the BNT162b2 
vaccine candidate in cases of:
•
Confirmed COVID-19
•
Confirmed severe COVID-19
•
SARS-CoV-2 infection 
without confirmed COVID-19
In each subset of evaluable 
maternal participants from each 
vaccine group with: 
•
Confirmed COVID-19
•
Confirmed severe 
COVID-19 
•
SARS-CoV-2 infection but 
no confirmed COVID-19
•
GMCs/GMTs and GMFRs 
at baseline, 1 month after 
Dose 2, at delivery, and 
6 months after delivery
•
Full-length S-binding IgG levels 
•
SARS-CoV-2 neutralizing titers
To describe the immune response 
to prophylactic BNT162b2 
between Dose 1 and Dose 2 when 
administered to maternal 
participants 18 years of age or 
older vaccinated at 27 to 34 
weeks’ gestation in the Phase 2
portion of the study.
In evaluable maternal 
participants: 
•
GMCs/GMTs at baseline 
and before Dose 2 
•
GMFRs from baseline to 
before Dose 2
•
Full-length S-binding IgG levels 
•
SARS-CoV-2 neutralizing titers
To describe the immune response 
in infants born to breastfeeding 
maternal participants vaccinated 
with prophylactic BNT162b2 
during pregnancy.
In infants born to maternal 
participants from each vaccine 
group, based on the 
breastfeeding status:
•
GMCs and GMFRs, at birth 
and 6 months after delivery
•
Full-length S-binding IgG levels
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Objectivesa
Estimands
Endpoints
To describe the safety of maternal 
immunization in infants born to 
breastfeeding maternal participants 
vaccinated with prophylactic 
BNT162b2 during pregnancy.
In infants born to maternal 
participants receiving at least 
1 dose of study intervention 
from each vaccine group, based 
on the breastfeeding status, the 
percentage of infants with:
•
AEs from birth through
1 month of age
•
SAEs and AESIs (major 
congenital anomalies, 
developmental delay) 
through 6 months of age
•
AEs from birth through 1 month 
of age
•
SAEs and AESIs (major 
congenital anomalies, 
developmental delay) through 
6 months of age
To describe the incidence of 
confirmed COVID-19 in infants 
born to maternal participants who 
were vaccinated with BNT162b2
during pregnancy.
In infants born to maternal 
participants from each vaccine 
group:
•
Incidence rate of infant 
participants with confirmed
COVID-19
•
COVID-19 incidence per 
1000 person-years of follow-up 
based on central laboratory or 
locally confirmed NAAT
To describe MIS-C cases in infants 
born to maternal participants who 
were vaccinated with BNT162b2 
during pregnancy.
In infants born to maternal 
participants from each vaccine 
group:
•
Incidence rate of MIS-C
•
MIS-C incidence per 
1000 person-years of follow-up
a.
HIV-infected participants will not be included in analyses of the objectives, but in separate exploratory 
analyses.  Analyses among HIV-infected women and their infants will be summarized separately.
4. STUDY DESIGN
4.1. Overall Design
This will be a global Phase 2/3, randomized, placebo-controlled, observer-blind study in 
approximately 350 healthy pregnant women 18 years of age or older vaccinated during 
their 24 to 34 weeks’ gestation. This study will evaluate the safety, tolerability, and 
immunogenicity of 2 doses of BNT162b2 or placebo administered 21 days apart.  The 
Phase 2 portion of the study will include approximately 200 pregnant women randomized 1:1 
to receive BNT162b2 or placebo (saline) during their 27 to 34 weeks’ gestation. Safety data
through 7 days after the second dose (where Day 1 is the day of vaccination) for all Phase 2 
participants will be reviewed by the Pfizer IRC. The Phase 3 portion of this study will assess 
the safety, tolerability, and immunogenicity of BNT162b2 in approximately 150 pregnant 
women enrolled during their 24 to 34 weeks’ gestation who will be randomized in a 1:1 ratio
to receive BNT162b2 or placebo (saline).  Phase 3 will proceed after the first 200 maternal
participants have been enrolled in Phase 2. Maternal participants who originally received 
placebo will receive BNT162b2 at defined time points as part of the study.
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Enrollment in this study was terminated on 25 Oct 2021 with approximately 350 participants 
enrolled.  Enrollment was terminated due to enrollment challenges into a placebo-controlled 
study as a result of universal recommendations for COVID-19 vaccination of pregnant 
women and the increased global availability of COVID-19 vaccines. Enrollment numbers 
within this protocol have been modified accordingly.
The study is observer-blinded, as the physical appearance of the investigational vaccine and 
the placebo may differ. The participant, investigator, study coordinator, and other site staff 
will be blinded through the 1-month postdelivery visit for each maternal participant.  At the 
study site, only the dispenser(s)/administrator(s) are unblinded.
Each maternal participant will participate in the study for approximately up to 10 months
depending on the vaccine group to which she was randomized. Her infant will participate in 
the study for approximately 6 months. The study duration will be approximately 14 months.
For each placebo recipient who will go on to receive BNT162b2 and follow a new visit 
schedule (Section 1.3.2), she will participate in the study for up to 7 months, and her infant 
will participate in the study for approximately 6 months.
The study will use an external DMC throughout study conduct. A Pfizer IRC will be used 
during the Phase 2 portion of the study to closely monitor safety.
The study will include stopping rules, which may result in a pause to study vaccination 
followed by a review and recommendation by the IRC.
4.2. Scientific Rationale for Study Design
There are currently no licensed vaccines to prevent infection with SARS-CoV-2 or 
COVID-19.  Pregnant women are at risk of acquiring SARS-CoV-2 infection, developing 
COVID-19 and COVID-19–associated complications. Given the global crisis of COVID-19 
and fast expansion of the disease globally, the rapid development of an effective vaccine for 
use in this population is of utmost importance.
This study is being conducted as a standard maternal immunization safety and 
immunogenicity clinical trial; however, additional surveillance for COVID-19 has been 
included as part of the study to assess efficacy (based on a minimal number of cases) as well 
as to monitor the potential risk of disease enhancement and severe disease in pregnant 
women and their infants with COVID-19.  If a participant experiences symptoms, as detailed 
in Section 8.13, a COVID-19 illness and subsequent convalescent visit will occur.  As part of 
these visits, samples (nasal swab and blood) will be taken for antigen and antibody 
assessment as well as recording of COVID-19–related clinical and laboratory information 
(including local diagnosis).
4.3. Justification for Dose
Based on data from the Phase 1 component of clinical trial C4591001, the BNT162b2 
vaccine candidate was selected at a dose of 30 μg for Phase 2/3 evaluation in C4591001.
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4.4. End of Study Definition
A participant and her infant are considered to have completed the study if they have
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 participant in the study.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. Use of a 
prescreener for study recruitment purposes will include collection of information that reflects 
the enrollment of a diverse participant population including, where permitted under local 
regulations, age, sex, race, and ethnicity.  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
Participants are eligible to be included in the study only if all of the following criteria apply.
NOTE: 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.
Maternal participants must provide informed consent prior to performing any procedures, 
including those that are being done exclusively to meet study eligibility criteria.
5.1.1. Maternal Participants
Age and Sex:
1. Healthy women ≥18 years of age who are between 24 0/7 and 34 0/7 weeks’ gestation on 
the day of planned first vaccination, with an uncomplicated, singleton pregnancy, who 
are at no known increased risk for complications.
a.
Phase 2 participants will include healthy women ≥18 years of age who are between 
27 0/7 and 34 0/7 weeks’ gestation on the day of planned vaccination, with an 
uncomplicated, singleton pregnancy, who are at no known increased risk for 
complications.
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GA will be documented based on one of the following composite criteria based on timing 
and availability of data on the LMP, ultrasound examination, and physical examination, for 
natural pregnancies. Please refer to the SRM for GA dating among women who underwent 
assisted reproduction technology. 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.
•
If there is a discrepancy of >7 days between the LMP-determined GA and a 
first-trimester ultrasound OR the LMP is uncertain/unknown, then the GA should be 
determined using the first-trimester ultrasound.
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 or a physical examination including 
fundal height.
•
If there is a discrepancy of >10 days between the LMP-determined GA and the 
second-trimester ultrasound OR if the LMP is uncertain/unknown, then the GA 
should be determined using the second-trimester ultrasound.
c.
Third-Trimester Data Available (data obtained at ≥28 weeks):
•
The date of the first day of the reported LMP may be used to establish the GA if 
corroborated by a third-trimester ultrasound or a physical examination including 
fundal height.
•
If there is a discrepancy of >21 days between the LMP-determined GA and the 
third-trimester ultrasound OR if the LMP is uncertain/unknown, then the GA should 
be determined using the third-trimester ultrasound.
Type of Participant and Disease Characteristics:
2. Participants who are 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.
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5. Healthy participants who are determined by medical history, physical examination, and 
clinical judgment to be appropriate for inclusion in the study. Note: Participants with 
preexisting stable disease, defined as disease not requiring significant change in therapy 
or hospitalization for worsening disease during the 6 weeks before enrollment, can be 
included. Specific criteria for Phase 3 participants with known stable infection with HIV, 
HCV, or HBV can be found in Section 10.4.
6. Documented negative HIV antibody test (Phase 2 only), syphilis test, and 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 
conducted.
8. Expected to be available for the duration of the study and can be contacted by telephone 
during study participation. Country-specific modification for Mozambique: Participants 
are expected to be available for the duration of the study and to reside in the Manhiça 
study area.
9. Participant is willing to give informed consent for her infant to participate in the study.
Weight:
10. Prepregnancy 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.
Informed Consent:
11. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the ICD and in this protocol.
5.1.2. Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s).
•
The maternal participant must sign an ICD for herself and her fetus/infant before
taking part in the study.  The father of the fetus/infant must sign an ICD if required by 
local requirements.
2. Parent(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
Participants are excluded from the study if any of the following criteria apply:
5.2.1. Maternal Participants
Medical Conditions:
1. Other medical or psychiatric condition including recent (within the past year) or active 
suicidal ideation/behavior or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the
study.
2. Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT 
result was not available) or microbiological (based on COVID-19 symptoms/signs and a 
positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study intervention or any related 
vaccine.
4. Participants with known or suspected immunodeficiency.
5. Bleeding diathesis or condition associated with prolonged bleeding that would in the 
opinion of the investigator contraindicate intramuscular injection.
6. Phase 2 only: A prior or current major illness of the mother or conditions of the fetus 
that, in the investigator’s judgment, will substantially increase the risk associated with the 
participant’s participation in, and completion of, the study or could preclude the 
evaluation of the participant’s response, including but not limited to the following:
•
Gestational hypertension or preeclampsia-eclampsia
•
Placental abnormality
•
Polyhydramnios or oligohydramnios
•
Significant bleeding or blood clotting disorder
•
Gestational diabetes 
•
Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth
•
Prior stillbirth or neonatal death, prior low birth weight or preterm delivery, prior 
history of at least 3 miscarriages, prior pregnancies numbering greater than 5, or 
previous infant with a known genetic disorder or major congenital anomaly
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7. For Phase 2 only: Maternal participants with a history of stable chronic diseases that 
are known to be associated with increased risk of obstetrical or neonatal complications 
(as defined above in exclusion criterion 6) should not be included.
8. Phase 3: Current major illness of the mother or conditions of the fetus that, in the 
investigator’s judgment, will substantially increase the risk associated with the 
participant’s participation in, and completion of, the study or could preclude the 
evaluation of the participant’s response, including but not limited to the following:
•
Uncontrolled gestational hypertension
•
Preeclampsia-eclampsia
•
Placental abnormality
•
Polyhydramnios or oligohydramnios
•
Significant bleeding or blood clotting disorder
•
Uncontrolled gestational diabetes 
•
Any signs of premature labor with the current pregnancy or having ongoing 
intervention (medical/surgical) in the current pregnancy to prevent preterm birth
•
Prior stillbirth or neonatal death, preterm delivery (≤34 weeks), or previous infant 
with a known genetic disorder or major congenital anomaly.
Prior/Concomitant Therapy:
9. Previous vaccination with any coronavirus vaccine.
10. Receipt of medications intended to prevent COVID-19.
11. Receipt of blood/plasma products or immunoglobulin, from 60 days before 
administration of study intervention, or planned receipt through delivery, with 
1 exception, anti-D immunoglobulin (eg, RhoGAM), which can be given at any time.
12. Current alcohol abuse or illicit drug use.
13. Participants who receive treatment with immunosuppressive therapy, including cytotoxic 
agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned 
receipt through the postvaccination blood draw.
Prior/Concurrent Clinical Study Experience:
14. Participation in other studies involving study intervention within 28 days prior to study 
entry and/or during study participation.
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15. Previous participation in other studies involving study intervention containing LNPs.
Diagnostic Assessments:
16. Not applicable.
Other Exclusions:
17. Investigator site staff or Pfizer employees directly involved in the conduct of the study, 
site staff otherwise supervised by the investigator, and their respective family members.
18. Participants whose unborn baby has been fathered by investigational site staff members 
directly involved in the conduct of the study or their family members, site staff members 
otherwise supervised by the investigator, or Pfizer employees directly involved in the 
conduct of the study.
5.2.2. Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
5.3. Lifestyle Considerations
No restrictions 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 study intervention. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the CONSORT publishing requirements and to respond to queries from 
regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any SAE.
Maternal participants who do not meet the criteria for participation in this study (screen 
failure) may be rescreened.
5.5. Criteria for Temporarily Delaying Randomization/Study Intervention 
Administration 
The following conditions are temporary or self-limiting and a maternal participant may be 
vaccinated once the condition(s) has/have resolved and no other exclusion criteria are met.
1. Current febrile illness (temperature 38.0°C [100.4°F]) or other acute illness within 
48 hours before study intervention administration. This includes current symptoms that 
could represent a potential COVID-19 illness:
•
New or increased cough;
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•
New or increased shortness of breath;
•
Chills; 
•
New or increased muscle pain;
•
New loss of taste/smell;
•
Sore throat;
•
Diarrhea;
•
Vomiting.
2. Receipt of any seasonal or pandemic influenza vaccine in the previous 14 days.
3. Anticipated receipt of any seasonal or pandemic influenza vaccine in the 7 days after 
study intervention administration.
4. Receipt of a tetanus-, diphtheria-, and/or pertussis-containing vaccine in the previous 
14 days.
5. Anticipated receipt of a tetanus-, diphtheria-, and/or pertussis-containing vaccine in the 
7 days after study intervention administration.
6. Receipt of short-term (<14 days) systemic corticosteroids.  Study intervention 
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.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
The study will evaluate 2 doses of BNT162b2 or placebo administered 21 days apart for 
active immunization against COVID-19 in healthy pregnant women 18 years of age or older 
vaccinated during their 24 to 34 weeks’ gestation. The Phase 2 portion of the study will 
include a subset (N=200) of pregnant women during their 27 to 34 weeks’ gestation.
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The investigational RNA vaccine candidate or saline placebo are the 2 potential study 
interventions that may be administered to pregnant maternal participants (randomized 1:1):
•
BNT162b2 (BNT162 RNA-LNP vaccine utilizing modRNA and encoding the P2 S): 
30 μg
•
Normal saline (0.9% NaCl solution for injection)
6.1. Study Intervention(s) Administered
Intervention Name
BNT162b2 
(BNT162 RNA-LNP Vaccine 
Utilizing modRNA)
Saline Placebo
Type
Vaccine
Placebo
Dose Formulation
modRNA
Normal saline (0.9% NaCl solution 
for injection)
Unit Dose Strength(s)
250 μg/0.5 mL
N/A
Dosage Level(s)
30-μg
N/A
Route of Administration
Intramuscular injection
Intramuscular injection
Use
Experimental
Placebo
IMP or NIMP
IMP
IMP
Sourcing
Provided centrally by the sponsor
Provided centrally by the sponsor
Packaging and Labeling
Study intervention will be provided in 
a glass vial as open-label supply.
Each vial will be labeled as required 
per country requirement.
Study intervention will be provided 
in a glass or plastic vial as open-label 
supply. Each vial will be labeled as 
required per country requirement.
6.1.1. Administration
Maternal participants will receive 1 dose of study intervention as randomized at each 
vaccination visit (Visits 1 and 2) in accordance with the study’s SoA (Section 1.3.1).  Full 
details are described in the IP manual.
At 1 month after delivery, maternal participants who originally received placebo will receive 
1 dose of BNT162b2 at each additional vaccination visit (Visits 101 and 102) in accordance 
with the SoA in Section 1.3.2.
Study intervention should be administered intramuscularly into the deltoid muscle, preferably 
of the nondominant arm, by an unblinded administrator.
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 study interventions should be performed by an appropriately qualified, 
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.
Study intervention administration details will be recorded on the CRF.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm that 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.
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 
temperatures since previously documented for all site storage locations upon return to 
business.
3. 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.  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.
4. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the label.
5. Study interventions should be stored in their original containers.
6. See the IP manual for storage conditions of the study intervention.
7. 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), such as the IPAL or 
sponsor-approved equivalent. All study interventions will be accounted for using a study 
intervention accountability form/record.
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8. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual.  All destruction must be adequately documented.  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.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual.
6.2.1. Preparation and Dispensing
See the IP manual for instructions on how to prepare the study intervention for 
administration.  Study intervention 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.  A second staff member will verify the dispensing.
Study intervention and placebo will be prepared by qualified unblinded site personnel 
according to the IP manual.  The study intervention will be administered in such a way as to 
ensure that the maternal participants remain blinded.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Maternal participants will be allocated (randomized) to a vaccine group as described below. 
The infants of the maternal participants will be assigned a participant number at birth.
Allocation of maternal participants to vaccine groups will proceed through the use of an IRT 
system (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 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 DU or container number 
when study intervention 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.
Study intervention will be dispensed at the study visits 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 study intervention according to 
randomization scheme.  Investigators will remain blinded to each maternal participant’s 
assigned study intervention until 1 month after delivery.
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6.3.2. Blinding of Site Personnel Until the 1-Month Postdelivery Visit
In this observer-blinded study, the study staff receiving, storing, dispensing, preparing, and 
administering the study interventions will be unblinded.  All other study and site personnel, 
including the investigator, investigator staff, and maternal participants, will be blinded to 
study intervention assignments.  In particular, the individuals who evaluate maternal 
participant safety will be blinded.  Because the BNT162 RNA-based COVID-19 vaccine 
candidate and placebo are different in physical appearance, the study intervention syringes 
will be administered in a manner that prevents the maternal study participants from 
identifying the study intervention type based on its appearance.
The responsibility of the unblinded dispenser and administrator must be assigned to an 
individual or individuals who will not participate in the evaluation of any maternal study 
participants.  Contact between the unblinded dispenser and maternal study participants and 
unblinded administrator and maternal study participants should be kept to a minimum.  The 
remaining site personnel must not know study intervention assignments.
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the site(s) to verify that randomization/dispensing has been done 
accurately.
To allow administration of BNT162b2 to maternal participants who originally received 
placebo, site staff will be unblinded to individual participants’ original study intervention 
allocation at the 1-month postdelivery visit.
6.3.3. Blinding of Site Personnel Prior to the 1-Month Postdelivery Visit
To allow administration of BNT162b2 to maternal participants who originally received 
placebo, site staff will be unblinded to individual participants’ original study intervention 
allocation at the 1-month postdelivery visit.  Prior to unblinding maternal participants at the 
1-month postdelivery visit, this is an observer-blinded study. The study staff receiving, 
storing, dispensing, preparing, and administering the study interventions will be unblinded.  
All other study and site personnel, including the investigator, investigator staff, and maternal 
participants, will be blinded to study intervention assignments until the 1-month postdelivery
visit for each participant.  In particular, the individuals who evaluate maternal participant 
safety prior to unblinding maternal participants at the 1-month postdelivery visit will be 
blinded.
Because the BNT162 RNA-based COVID-19 vaccine candidate and placebo are different in 
physical appearance, the study intervention syringes will be administered in a manner that 
prevents the maternal study participants from identifying the study intervention type based on 
its appearance during the blinded portion of the study.
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The responsibility of the unblinded dispenser and administrator must be assigned to an 
individual or individuals who will not participate in the evaluation of any maternal study 
participants prior to the maternal participant being unblinded.  Contact between the 
unblinded dispenser and blinded maternal study participants and unblinded administrator and 
blinded maternal study participants should be kept to a minimum.  The remaining site 
personnel must not know study intervention assignments until the maternal participant is 
unblinded at the 1-month postdelivery visit.
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the site(s) to verify that randomization/dispensing has been done 
accurately.
6.3.4. Blinding of the Sponsor
The study team will be unblinded to the participant’s study intervention allocation when 
maternal participants complete the 1-month postdelivery visit. Prior to unblinding the 
maternal participants at the 1-month postdelivery visit the majority of sponsor staff will be 
blinded to study intervention allocation.  All laboratory testing personnel performing 
serology assays will remain blinded to study intervention assigned/received.  The following 
sponsor staff, who will have no part in the blinded conduct of the study, will be unblinded 
(further details will be provided in a data blinding plan):
•
Those study team members who are involved in ensuring that protocol requirements for 
study intervention preparation, handling, allocation, and administration are fulfilled at the 
site will be unblinded for the duration of the study (eg, unblinded study manager, 
unblinded clinical research associate).
•
Unblinded clinician(s) who are not direct members of the study team and will not 
participate in any other study-related activities will review unblinded protocol deviations.
•
An unblinded team supporting interactions with, and analyses for, the DMC 
(see Section 9.6).  This will comprise a statistician, programmer(s), and a medical 
monitor and/or a clinical scientist who will review cases of severe COVID-19 as they are 
received, and will review AEs at least weekly for additional potential cases of severe 
COVID-19 (see Section 8.2.4).
•
An unblinded submissions team will be responsible for preparing unblinded analyses and 
documents to support regulatory activities that may be required while the study is 
ongoing.  This team will only be unblinded at the group level and not have access to 
individual participant assignments.  The programs that produce the summary tables will 
be developed and validated by the blinded study team, and these programs will be run by 
the unblinded DMC team.
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6.3.5. Breaking the Blind
The IRT will be programmed with blind-breaking instructions.  In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a maternal
participant’s vaccine assignment is warranted. Participant safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the sponsor prior to 
unblinding a maternal participant’s vaccine assignment unless this could delay further 
management of the participant.
If a maternal participant’s vaccine assignment is unblinded, the sponsor must be notified 
within 24 hours after breaking the blind. The date and reason that the blind was broken must 
be recorded in the source documentation and 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.
Instructions on how to unblind participants ahead of administration of BNT162b2 to placebo 
recipients will be provided separately: this unblinding will NOT be performed in the IRT.
6.4. Study Intervention Compliance
When maternal participants are dosed at the site, they will receive study intervention directly 
from the investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF.  
The dose of study intervention and maternal study participant identification will be 
confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention.
6.5. Concomitant Therapy
6.5.1. Prohibited During the Study – Maternal Participants
Receipt of the following vaccines and medications during the time periods listed below may 
exclude a maternal participant from the per-protocol analysis from that point onwards, and 
may require vaccinations to be discontinued in that participant; however, it is anticipated that 
the maternal participant would not be withdrawn from the study (see Section 7).  Medications
should not be withheld if required for a maternal participant’s medical care.
•
Unless considered medically necessary, no vaccines other than study intervention should 
be administered within 14 days before and 7 days after each study vaccination, including 
seasonal and pandemic influenza vaccines.
•
Receipt of chronic systemic treatment with known immunosuppressant medications 
within 60 days before enrollment through conclusion of the study.
•
Receipt of systemic corticosteroids (≥20 mg/day of prednisone or equivalent) 
for ≥14 days is prohibited from 28 days prior to enrollment through Visit 3.
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•
Receipt of blood/plasma products or immunoglobulins within 60 days before enrollment 
through conclusion of the study.
•
Receipt of any other (nonstudy) coronavirus vaccine at any time prior to or during study 
participation is prohibited.
•
Prophylactic antipyretics and other pain medication to prevent symptoms associated with 
study intervention administration are not permitted.  However, if a maternal participant is 
taking a medication for another condition, even if it may have antipyretic or 
pain-relieving properties, it should not be withheld prior to study vaccination.
6.5.2. Permitted During the Study – Maternal Participants
•
The use of antipyretics and other pain medication to treat symptoms associated with 
study intervention administration or ongoing conditions is permitted.
•
Medication other than that described as prohibited in Section 6.5.1 required for treatment 
of preexisting stable conditions is permitted.
•
Inhaled, topical, or localized injections of corticosteroids (eg, intra-articular or intrabursal 
administration) are permitted.
6.5.3. Recording Nonstudy Vaccinations and Concomitant Medications – Maternal 
Participants
The following concomitant medications and vaccinations will be recorded in the CRF:
•
All vaccinations received from 14 days prior to study enrollment until the 6-month 
follow-up visit for participants originally randomized to receive BNT162b2.
•
Any medication taken to treat AEs from the signing of the ICD through the final study 
visit be recorded in the CRF.
•
Prohibited medications listed in Section 6.5.1 will be recorded in the CRF, to include 
start and stop dates, name of the medication, dose, unit, route, and frequency from the 
signing of the ICD through the final study visit.
6.5.4. Prohibited During the Study – Infant Participants
•
Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study.
6.5.5. Permitted During the Study – 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.
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•
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 Concomitant Medications – Infant Participants
The following concomitant medications will be recorded in the CRF:
•
Any medications taken to treat AEs and/or SAEs from Visit 1 through the final study 
visit.
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 maternal or infant study participants at the end of the 
study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following: AEs; participant request; investigator request; protocol 
deviation (including no longer meeting all the inclusion criteria, or meeting 1 or more 
exclusion criteria). In general, unless the investigator considers it unsafe to administer the 
second dose, or the maternal participant does not wish to receive it, it is preferred that the 
second dose be administered. Note: following Vaccination 1, a positive SARS-CoV-2 
NAAT result without symptoms or a COVID-19 diagnosis (signs/symptoms only or 
signs/symptoms and a positive SARS-CoV-2 NAAT result) should not result in 
discontinuation from the study intervention.
Note that discontinuation of study intervention does not represent withdrawal from the study.  
Per the study estimands if study intervention is definitively discontinued, the participant will 
remain in the study to be evaluated for safety, tolerability, and immunogenicity. See the SoA
for data to be collected at the time of discontinuation of study intervention and follow-up for 
any further evaluations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, postvaccination study follow-up, 
and/or future collection of additional information.
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7.2. Participant Discontinuation/Withdrawal From the Study
A maternal participant may withdraw from the study at any time at her own request or the 
infant participant may be withdrawn at any time at the request of his/her parent(s).  Reasons 
for discontinuation from the study include the following:
•
Refused further follow-up;
•
Lost to follow-up;
•
Death;
•
Study terminated by sponsor;
•
AEs;
•
Maternal participant request; 
•
Investigator request;
•
Protocol deviation.
If a participant does not return for a scheduled visit, every effort should be made to contact 
the participant.  All attempts to contact the participant and information received during 
contact attempts must be documented in the participant’s source document.  In any 
circumstance, every effort should be made to document participant outcome, if possible.
The investigator or his or her designee should capture the reason for withdrawal in the CRF 
for all participants.
If a participant withdraws from the study, she may request destruction of any remaining 
samples taken and not tested, and 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 Section 7.2.1) 
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.
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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7.2.1. Withdrawal of Consent
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with her.  Participants 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 further receipt of study intervention or also from study procedures and/or 
postvaccination study follow-up, and entered on the appropriate CRF page.  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.
7.3. Lost to Follow-up
A maternal participant will be considered lost to follow-up if 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 for scheduled visits and is 
unable to be contacted by the study site:
•
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant 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 continue to be unreachable, she will be considered to have 
withdrawn from the study.
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.
The full date of birth will be collected to critically evaluate the immune response and safety 
profile by age.
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Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether 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 maternal 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all maternal 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 and/or screening purposes 
provided the procedures met the protocol-specified criteria and were performed within the 
time frame defined in the SoA.
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.
The total blood sampling volume in this study is dependent on when a maternal participant is 
enrolled and which vaccine she is given while pregnant. It is expected that most maternal 
participants will have to give up to 6 blood samples (20 mL each).
Additionally, 20 mL of blood for maternal participants will be taken at an unplanned 
convalescent visit at any time a maternal participant develops respiratory symptoms 
indicating a potential COVID-19 infection. Maternal participants would therefore have a 
total blood sampling volume of approximately up to 140 mL during the study period.  
Additional blood samples may be taken for safety assessments at times specified by Pfizer, 
provided the total volume taken during the study does not exceed 550 mL during any period 
of 60 consecutive days.  Approximately 10 mL of cord blood will be taken from each infant 
participant; if cord blood is unavailable, a blood sample of up to 5 mL (based on weight) will 
be collected. A 5-mL blood sample will be collected from each infant at the 6-month 
postdelivery visit; in addition, a blood sample of up to 5 mL will be collected at each 
convalescent illness visit.
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8.1. Efficacy and/or Immunogenicity Assessments
Surveillance for potential cases of COVID-19 will occur throughout a maternal and infant 
participant’s involvement in the study.  If, at any time, a maternal or infant participant 
develops acute respiratory illness (see Section 8.13), for the purposes of the study he or she
will be considered to potentially have a COVID-19 illness.  In this circumstance, the 
maternal participant should contact the site, an in-person or telehealth visit should occur, and 
assessments should be conducted as specified in the SoA.  The assessments will include 
collection of a nasal swab, which will be tested at a central laboratory using an RT-PCR test 
(Cepheid; FDA approved under EUA), or other equivalent nucleic acid amplification–based 
test (ie, NAAT), to detect SARS-CoV-2.  In addition, clinical information and results from 
local standard-of-care tests (as detailed in Section 8.13) will be assessed.  The central 
laboratory NAAT result will be used for the case definition, unless no result is available from 
the central laboratory, in which case a local NAAT result may be used if it was obtained 
using 1 of the following assays:
•
Cepheid Xpert Xpress SARS-CoV-2
•
Roche cobas SARS-CoV-2 real-time RT-PCR test (EUA200009/A001)
•
Abbott Molecular/RealTime SARS-CoV-2 assay (EUA200023/A001)
8.1.1. Maternal Participants
Two definitions of SARS-CoV-2–related cases, and SARS-CoV-2–related severe cases, will 
be considered (for both, the onset date of the case will be the date that symptoms were first 
experienced by the maternal participant; if new symptoms are reported within 4 days after 
resolution of all previous symptoms, they will be considered as part of a single illness):
Confirmed COVID-19, first definition: presence of at least 1 of the following symptoms 
and SARS-CoV-2 NAAT-positive during, or within 4 days before or after, the symptomatic 
period, either at the central laboratory or at a local testing facility (using an acceptable test):
•
Fever; 
•
New or increased cough; 
•
New or increased shortness of breath; 
•
Chills;
•
New or increased muscle pain; 
•
New loss of taste or smell;
•
Sore throat;
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•
Diarrhea;
•
Vomiting.
The second definition, which may be updated as more is learned about COVID-19, will 
include the following additional symptoms defined by the CDC (listed at 
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html):
•
Fatigue;
•
Headache;
•
Nasal congestion or runny nose;
•
Nausea.
Confirmed Severe COVID-19: confirmed COVID-19 and presence of at least 1 of the 
following:
•
Clinical signs at rest indicative of severe systemic illness (RR ≥30 breaths/min, 
HR ≥125 beats/min, SpO2 ≤93% on room air at sea level, or PaO2/FiO2 <300 mm Hg);
•
Respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, 
mechanical ventilation, or ECMO);
•
Evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors);
•
Significant acute renal, hepatic, or neurologic dysfunction*;
•
Admission to an ICU;
•
Death.
The second definition, which may be updated as more is learned about COVID-19, will 
include the following additional outcomes defined by the CDC (listed at 
https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-
conditions.html):
•
Hospitalization;
•
Admission to the ICU;
•
Intubation or mechanical ventilation;
•
Death.
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8.1.2. Infant Participants
Two definitions of SARS-CoV-2–related cases, and SARS-CoV-2–related severe cases, will 
be considered (for both, the onset date of the case will be the date that symptoms were first 
experienced by the infant participant; if new symptoms are reported within 4 days after 
resolution of all previous symptoms, they will be considered as part of a single illness). 
Signs and symptoms of an acute respiratory illness will not be considered a potential 
COVID-19–related illness if they occur within the first 72 hours after birth.
Confirmed COVID-19, first definition: presence of at least 1 of the following symptoms 
and SARS-CoV-2 NAAT-positive during, or within 4 days before or after, the symptomatic 
period, either at the central laboratory or at a local testing facility (using an acceptable test):
•
Fever; 
•
New or increased cough; 
•
New or increased shortness of breath; 
•
Diarrhea;
•
Vomiting.
The second definition, which may be updated as more is learned about COVID-19, will 
include the following additional symptoms defined by the CDC (listed at 
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) but does not 
trigger a potential COVID-19 illness visit unless, in the opinion of PI, it is deemed necessary:
•
Nasal congestion or runny nose;
•
Poor appetite or poor feeding;
•
Abdominal pain (colic).
Confirmed Severe Infant COVID-19: confirmed COVID-19 and presence of at least 1 of 
the following:
•
Clinical signs at rest indicative of severe systemic illness:
•
RR (breaths/min): >50 from birth to 1 week of age, ≥40 from 1 week to 1 month of 
age, ≥34 from 1 month to 6 months of age;
•
HR (beats/min): >180;
•
SpO2 ≤92% on room air or >50% FiO2 to maintain ≥92%, or PaO2/FiO2
<300 mm Hg;33
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•
Respiratory failure (defined as needing high-flow oxygen including nasal CPaP/BiPaP, 
noninvasive ventilation, mechanical ventilation, or ECMO);
•
Evidence of shock or cardiac failure:
•
SBP (mm Hg) (<5th percentile for age):
•
<65 from birth to 1 week of age, <75 from 1 week to 1 month of age, <100 from 
1 month to 6 months of age;
OR
•
Requiring vasoactive drugs to maintain BP in the normal range;
•
Significant acute renal failure: serum creatinine >2 times ULN for age or 2-fold increase 
in baseline creatinine;
•
Significant GI/hepatic failure: total bilirubin >4 mg/dL or ALT 2 times ULN for age; 
•
Significant neurologic dysfunction: Glasgow Coma Scale score <11 or acute change in 
mental status with a decrease in Glasgow Coma Scale score ≥3 points from abnormal 
baseline;
•
Admission to an ICU;
•
Death.
Confirmed Multisystem Inflammatory Syndrome in Children (MIS-C) definition34:
as per the CDC MIS-C case definition:
•
An infant presenting with fever (≥38.0°C for ≥24 hours or report of subjective fever 
lasting ≥24 hours); AND
•
Laboratory evidence of inflammation (based on local laboratory ranges) including, but 
not limited to, 1 or more of the following: an elevated CRP, ESR, fibrinogen, 
procalcitonin, D-dimer, ferritin, LDH, or IL-6, elevated neutrophils, reduced
lymphocytes, and low albumin; AND
•
Evidence of clinically severe illness requiring hospitalization (definition as noted above 
for severe disease), with multisystem (≥2) organ involvement:
o
Cardiac (eg, shock, elevated troponin, elevated BNP, abnormal echocardiogram, 
arrhythmia);
o
Renal (eg, acute kidney injury or renal failure);
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o
Respiratory (eg, pneumonia, ARDS, pulmonary embolism);
o
Hematologic (eg, elevated D-dimers, thrombophilia, or thrombocytopenia);
o
GI/hepatic (eg, elevated bilirubin, elevated liver enzymes, or diarrhea);
o
Dermatologic (eg, rash, mucocutaneous lesions);
o
Neurological (eg, CVA, aseptic meningitis, encephalopathy); AND
•
No alternative plausible diagnoses; AND
•
Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen 
test; OR 
•
COVID-19 exposure within the 4 weeks prior to the onset of symptoms.
The following are applicable for both maternal and infant participants:
The DMC may recommend modification of the definition of severe disease according to 
emerging information.
* A small group of blinded case reviewers (medically qualified Pfizer staff members) will 
review all potential COVID-19 illness events.  If a NAAT-confirmed case in Phase 2/3 may 
be considered severe, or not, solely on the basis of these criteria, the blinded data will be 
reviewed by the case reviewers to assess whether the criterion is met; the majority opinion 
will prevail.
In addition, a serological definition will be used for participants without clinical presentation 
of COVID-19:
•
Confirmed seroconversion to SARS-CoV-2 without confirmed COVID-19: a positive 
N-binding antibody result in a participant with a prior negative N-binding antibody result.
8.1.3. Immunogenicity
Serum samples will be obtained for immunogenicity testing at the visits specified in the SoA.
The following assays will be performed:
•
SARS-CoV-2 neutralization assay
•
Full-length S-binding IgG levels
•
N-binding antibody assay
Note that all immunogenicity analyses will be based upon samples analyzed at the 
central laboratory.
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8.1.4. Total Volume of Blood Collected – Maternal Participants
The total volume of blood collected for antibody assessment over the course of the study will 
be up to approximately 120 mL (~20 mL/visit) and an additional 20 mL during each 
unplanned convalescent visit at any time a participant develops respiratory symptoms 
indicating a potential COVID-19 infection.
8.1.5. Total Volume of Blood Collected – Infant Participants
Blood samples will be collected according to the directive 2001/20/EC: Ethical
considerations for clinical trials on medicinal products conducted with minors.35
All infants will have a cord blood sample collected at birth. The total volume of cord blood 
to be collected for antibody assessment in this study will be approximately 10 mL.
If cord blood is unavailable, a blood sample may be collected from the infant participant up
to 72 hours 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 1).
The maximum volume of blood collected from the infant in the absence of cord blood will be
no more than 5 mL at planned study visits (based on weight). An additional sample of up 
to 5 mL may be collected during each unplanned convalescent visit at any time an infant
participant develops respiratory symptoms indicating a potential COVID-19 infection.
Table 1.
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 - ≤2.4
1.0
>2.4 - ≤3.7
2.0
>3.7 - ≤4.9
3.0
>4.9 - ≤6.2
4.0
>6.2
5.0
8.1.6. Biological Samples
Blood and nasal swab 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 
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 testing of the participant’s DNA material will be performed.
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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 participant’s DNA material 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 issues.
A clinical assessment, including medical history, will be performed on all maternal 
participants at the first visit to establish a baseline. Significant medical history and 
observations from any physical examination will be documented in the CRF.
AEs and SAEs are collected, recorded, and reported as defined in Section 8.3.
Acute reactions within the first 30 minutes after vaccination will be assessed and documented 
in the AE CRF.
The safety parameters also include reactogenicity e-diary reports of local reactions and 
systemic events (including fever) and use of antipyretic medication that occur in the 7 days 
after administration of the study intervention, where Day 1 is the day of vaccination. 
Reactogenicity will not be collected in the e-diary for placebo recipients who subsequently 
receive BNT162b2 1 month following delivery. These prospectively self-reported 
occurrences of local reactions and systemic events are graded as described in Section 8.2.2.
8.2.1. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study.
8.2.2. Electronic Diary
Maternal participants will be required to complete a reactogenicity e-diary through an 
application (see Section 8.15) installed on a provisioned device or on the maternal 
participant’s own personal device.  Maternal participants will be asked to monitor and record 
local reactions, systemic events, and antipyretic medication usage for 7 days following 
administration of the study intervention, where Day 1 is the day of vaccination.  The 
reactogenicity e-diary allows recording of these assessments only within a fixed time 
window, thus providing the accurate representation of the participant’s experience at that 
time.  Data on local reactions, systemic events, and antipyretic medication usage reported in 
the reactogenicity e-diary will be transferred electronically to a third-party vendor, where 
they will be available for review by investigators and the Pfizer clinicians at all times via an 
internet-based portal.
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Maternal participants originally randomized to placebo who subsequently receive BNT162b2
1 month following delivery, will not complete a reactogenicity e-diary but will have their 
local reactions and systemic events detected and reported as AEs in accordance with 
Section 8.3.2.
If the maternal participant lives in an area with poor network connection (certain countries 
only), 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) where this system of follow-up is well established. Maternal 
participants may call the site and report additional local reactions and systemic events at any 
time during the Day 1 through 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 on Day 7 and use of antipyretic medication continuing on Day 7, 
the field worker will continue to visit the participant and record information until resolution.
At intervals agreed to by the vendor and Pfizer, these data will be transferred electronically 
into Pfizer's database for analysis and reporting.  These data do not need to be reported by the 
investigator in the CRF as AEs.
Investigators (or designee) will be required to review the reactogenicity e-diary data online at 
frequent intervals as part of the ongoing safety review.
The investigator or designee must obtain stop dates from the participant for any ongoing 
local reactions, systemic events, or use of antipyretic medication on the last day that the 
reactogenicity e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF.
8.2.2.1. Grading Scales
The grading scales used in this study to assess local reactions and systemic events as 
described below are derived from the FDA CBER guidelines on toxicity grading scales for 
healthy adult volunteers enrolled in preventive vaccine clinical trials.29
8.2.2.2. Local Reactions
During the reactogenicity e-diary reporting period, 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 reactogenicity e-diary.  If a local reaction persists beyond 
the end of the reactogenicity e-diary period following vaccination, the maternal participant 
will be requested to report that information.  The investigator/field staff will enter this 
additional information in the CRF.
Redness and swelling will be measured and recorded by the maternal participants/study staff 
member/field worker in measuring device units (range: 1 to 21) and then categorized during 
analysis as absent, mild, moderate, or severe based on the grading scale in Table 2.  
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Measuring device units can be converted to centimeters according to the following formula: 
1 measuring device unit = 0.5 cm.  Pain at the injection site will be assessed by the 
participant as absent, mild, moderate, or severe according to the grading scale in Table 2.
If a Grade 3 local reaction is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated.  Only an investigator or medically qualified person is able to classify a 
participant’s local reaction as Grade 4.  If a participant experiences a confirmed Grade 4 local 
reaction, the investigator must immediately notify the sponsor and, if it is determined to be 
related to the administration of the study intervention, further vaccinations will be 
discontinued in that participant.
Where appropriate, the site staff/field worker will educate the maternal participant regarding 
signs and symptoms that would prompt site contact.
Table 2.
Local Reaction Grading Scale
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially Life 
Threatening 
(Grade 4)
Pain at the 
injection site
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity 
Emergency room 
visit or 
hospitalization for 
severe pain
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 
(≥21 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 
(≥21 measuring 
device units)
Necrosis
8.2.2.3. Systemic Events
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.
During the reactogenicity e-diary reporting period, maternal participants will be asked to 
assess vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain, and new 
or worsened joint pain and to record the symptoms in the reactogenicity e-diary. 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 during 
the reactogenicity reporting period. The symptoms will be assessed by the maternal 
participant as absent, mild, moderate, or severe according to the grading scale in Table 3.
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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.
If a Grade 3 systemic event is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated.  Only an investigator or medically qualified person is able to classify a maternal 
participant’s systemic event as Grade 4.  If a maternal participant experiences a confirmed 
Grade 4 systemic event, the investigator must immediately notify the sponsor and, if it is 
determined to be related to the administration of the study intervention, further vaccinations 
will be discontinued in that maternal participant.
Table 3.
Systemic Event Grading Scale
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially Life 
Threatening 
(Grade 4)
Vomiting
1-2 times in 
24 hours
>2 times in 24 hours Requires IV 
hydration
Emergency room 
visit or 
hospitalization for 
hypotensive shock
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
Headache
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Fatigue/tiredness
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
Chills
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe chills
New or worsened
muscle pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe new or 
worsened muscle 
pain
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Table 3.
Systemic Event Grading Scale
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially Life 
Threatening 
(Grade 4)
New or worsened 
joint pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe new or 
worsened joint pain
Abbreviation: IV = intravenous.
8.2.2.4. Fever
In order to record information on fever, a thermometer will be given to maternal participants 
with instructions on how to measure oral temperature at home.  Temperature will be 
collected in the reactogenicity e-diary in the evening daily during the reactogenicity e-diary 
reporting period.  It will also be collected at any time during the reactogenicity e-diary data 
collection periods when fever is suspected.  Similarly, based on local practice in certain 
countries/locales, the study staff/field worker will call or visit maternal participants daily 
during the reactogenicity reporting period 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 reactogenicity e-diary.  Temperature will be measured and 
recorded to 1 decimal place.  Temperatures recorded in degrees Fahrenheit will be 
programmatically converted to degrees Celsius and then categorized during analysis 
according to the scale shown in Table 4.
If a fever of ≥39.0°C (102.1°F) is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated.  Only an investigator or medically qualified person is able to confirm a maternal 
participant’s fever as >40.0°C (>104.0°F).  If a maternal participant experiences a confirmed 
fever >40.0°C (>104.0°F), the investigator must immediately notify the sponsor and, if it is 
determined to be related to the administration of the study intervention, further vaccinations 
will be discontinued in that maternal participant.
Table 4.
Scale for Fever
≥38.0-38.4°C (100.4-101.1°F)
>38.4-38.9°C (101.2-102.0°F)
>38.9-40.0°C (102.1-104.0°F)
>40.0°C (>104.0°F)
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8.2.2.5. Antipyretic Medication
The use of antipyretic medication to treat symptoms associated with study intervention
administration will be recorded in the reactogenicity e-diary daily during the reporting period
(Day 1 through Day 7).
8.2.3. Stopping Rules
The following stopping rules are in place for all Phase 2 maternal participants, based on 
review of AE data and e-diary reactogenicity data, until the start of Phase 3. Stopping rules 
do not apply to maternal participants who initially received placebo and subsequently 
receive BNT162b2. These data will be monitored on an ongoing basis by the investigator 
(or medically qualified designee) and sponsor in order to promptly identify and flag any 
event that potentially contributes to a stopping rule.
In the event that sponsor personnel confirm that a stopping rule is met, the following actions 
will commence:
•
The IRC will review all appropriate data.
•
The stopping rule will PAUSE randomization and study intervention administration for 
participants receiving the first dose. Maternal participants scheduled to receive Dose 2 at 
the time of a study pause may proceed with vaccination.
•
The DMC will review all appropriate data.
•
For all participants vaccinated, all other routine study conduct activities, including 
ongoing data entry, reporting of AEs, participant reactogenicity e-diary completion, 
blood sample collection, and participant follow-up, will continue during the pause.
A stopping rule is met if any of the following rules occur after administration of 
investigational BNT162b2; data from placebo recipients will not contribute to the stopping 
rules.  Reactogenicity e-diary data confirmed by the investigator as being entered by the
participant in error will not contribute toward a stopping rule.
Stopping Rule Criteria:
1. If any participant vaccinated with BNT162b2 develops an SAE that is assessed by the 
investigator as possibly related, or for which there is no alternative, plausible, attributable 
cause.
2. If any participant vaccinated with BNT162b2 develops a Grade 4 local reaction or 
systemic event after vaccination that is assessed as possibly related by the investigator, or 
for which there is no alternative, plausible, attributable cause.
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3. If any participant vaccinated with BNT162b2 develops a fever >40.0°C (>104.0°F) for at 
least 1 daily measurement after vaccination that is assessed as possibly related by the 
investigator, or for which there is no alternative, plausible, attributable cause.
4. If any 2 participants vaccinated with BNT162b2 report the same or similar severe 
(Grade 3) AE after vaccination, assessed as possibly related by the investigator, or for 
which there is no alternative, plausible, attributable cause.
5. If any participant dies or requires ICU admission due to SARS-CoV-2 infection; if this 
stopping rule is met, all available clinical and preclinical safety and immunogenicity data 
should be reviewed to evaluate for enhanced COVID-19.
6. If any participant vaccinated with BNT162b2 experiences any of the following within 
7 days after vaccination, where Day 1 is the day of vaccination: severe vaginal bleeding 
(eg, partial abruption); severe preeclampsia; eclampsia; HELLP syndrome; 
life-threatening sequelae of preeclampsia (eg, pulmonary edema); stillbirth; or fetal loss.
7. If ≥2 maternal participants vaccinated with BNT162b2 experience premature delivery or 
preterm premature rupture of membranes within 14 days after vaccination.
8.2.4. Surveillance of Events That Could Represent Enhanced COVID-19
The unblinded team supporting the DMC, including an unblinded medical monitor, will 
review cases of severe COVID-19 as they are received and will review AEs at least weekly 
for additional potential cases of severe COVID-19.  At any point, the unblinded team may 
discuss with the DMC chair whether the DMC should review cases.
The purpose of these reviews will be to identify whether any features of each case appear 
unusual, in particular, greater in severity, compared to available information at the time of 
review.  Indicators of severity may include accelerated deterioration, need for hospitalization, 
need for ventilation, or death.
Observed rates of these indicators will be compared with what could be expected in a 
population similar to the study participants based upon available information at the time of 
review.
8.2.5. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study.
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 (or the parent[s] for the infant participant).
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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 the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1).
Each maternal participant and parent of the 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.
The procedures described in this section pertain to both the infant participant and maternal 
participant, unless otherwise indicated.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
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 study intervention), 
through and including a minimum of 28 calendar days after the last administration of the 
study intervention.
In this study, the investigator and site staff will ensure the active elicitation and collection of 
AEs and SAEs through Visit 4.
From Visit 4 through Visit 8, SAEs will be collected for maternal participants originally 
randomized to BNT162b2. In addition, AEs occurring up to 48 hours after blood draws and 
collection of nasal swabs that are related to study procedures must be reported in the CRF.
Additionally, for those maternal participants who originally received placebo but go on to 
receive BNT162b2 at Visit 101 and Visit 102, AEs and SAEs will be collected through and 
1 month after the second dose of BNT162b2 (Visit 103).
For the infant participant, the time period for actively eliciting and collecting nonserious AEs 
(“active collection period”) begins at birth and continues through and including 1 month after 
birth. SAEs and AESIs will be collected from birth through and including 6 months of age.
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 who are screen failures, the active collection period ends when 
screen failure status is determined.
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If the participant withdraws from the study and also withdraws 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.
Note: Potential COVID-19/MIS-C illnesses and their sequelae that are consistent with the 
clinical endpoint definition (Section 8.1) should not be recorded as AEs. These data will be 
captured to describe disease endpoints for lack-of-efficacy assessment data only on the 
relevant pages of the CRF, as these are expected endpoints.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the Vaccine SAE Reporting Form, if 
applicable, immediately upon awareness and under no circumstance 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 of 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 the mother 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 study 
intervention must be reported to Pfizer Safety.
For those SAEs or deaths that occur to the infant after the active collection period should be 
reported when the investigator believes the SAE or death has at least a reasonable possibility 
of being related to study intervention.
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8.3.1.2. Recording Nonserious AEs and SAEs in the CRF
All nonserious AEs and 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.
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 of 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.
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 7.3).
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, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Additional Exposure Scenarios That May Result From the Exposure to the Study 
Intervention
8.3.5.1. Environmental Exposure During Pregnancy
Environmental exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
study intervention, 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.
•
The scenarios below describe environmental exposures that could lead to an EDP:
•
A female is found to be pregnant while being exposed or having been exposed to 
study intervention by environmental exposure. Below are some examples:
•
A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by inadvertent product 
administration via needlestick.
•
A male family member or healthcare provider who has been exposed to the study 
intervention then exposes his female partner prior to or around the time of 
conception.
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The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The investigator must report 
information to Pfizer Safety using the Vaccine SAE Reporting Form and EDP Supplemental 
Form.  The initial information submitted should include the anticipated date of delivery 
(see below for information related to termination of pregnancy). Since the exposure 
information does not pertain to the 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 investigator site file.
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.
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).
Abnormal pregnancy outcomes are considered SAEs. 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 
follows: 
•
Spontaneous abortion including 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 study intervention.
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).
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8.3.5.2. Exposure During Breastfeeding
Exposure-during-breastfeeding reports are not expected for maternal participants who 
breastfeed a child delivered during the study.
Environmental exposure during breastfeeding occurs when a female family member or 
healthcare provider who reports that she is breastfeeding after having been exposed to the 
study intervention (eg, by inhalation or skin contact).  The investigator must report exposure 
during breastfeeding to Pfizer Safety within 24 hours of the investigator’s awareness, 
irrespective of whether an SAE has occurred. The information must be reported using the 
Vaccine SAE Reporting Form. When exposure during breastfeeding occurs in the setting of 
environmental exposure, the exposure information does not pertain to the participant enrolled 
in the study, so the information is not recorded on a CRF. However, a copy of the completed 
Vaccine SAE Reporting Form is maintained in the investigator site file.
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, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE.  Such persons 
may include healthcare providers, family members, and other roles that are involved in the 
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE.  The information 
must be reported using the Vaccine SAE Reporting Form.  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 
investigator site file.
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
Potential COVID-19/MIS-C illnesses and their sequelae that are consistent with the clinical 
endpoint definition should not be recorded as AEs. These data will be captured as efficacy 
assessment data only on the relevant pages of the CRF, as these are expected endpoints.
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Potential COVID-19/MIS-C illnesses and their sequelae will not be reported according to the 
standard process for expedited reporting of SAEs, even though the event may meet the 
definition of an SAE.  These events will be recorded on the COVID-19 illness pages in the 
participant’s CRF within 1 day.
NOTE: However, if either of the following conditions applies, then the event must be 
recorded and reported as an SAE (instead of a disease-related event):
The event is, in the investigator’s opinion, of greater intensity, frequency, or duration 
than expected for the individual participant.
OR
The investigator considers that there is a reasonable possibility that the event was related 
to study intervention.
Potential COVID-19/MIS-C illness events and their sequelae will be reviewed by a group of 
internal blinded case reviewers.  Any SAE that is determined by the internal case reviewers 
NOT to meet endpoint criteria is reported back to the investigator site of incidence.  The 
investigator must report the SAE to Pfizer Safety within 24 hours of being made aware that 
the SAE did not meet endpoint criteria.  The investigator’s SAE awareness date is the date on 
which the investigator site of incidence receives the SAE back from the internal case 
reviewers.
8.3.8. Adverse Events of Special Interest
This section provides information on AESIs that may be detected during the study. The 
following events are considered AESIs:
•
A confirmed diagnosis of myocarditis or pericarditis. See Section 8.14 for additional 
procedures for monitoring of potential myocarditis or pericarditis.
For Infant Participants:
•
Major congenital anomaly
•
Developmental delay
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, as efficacy is yet to be demonstrated in the study population.
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8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors 
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Other exposures to the study intervention 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 study intervention;
•
Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant.
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 the 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.
Other examples include, but are not limited to:
•
The administration of expired study intervention;
•
The administration of an incorrect study intervention;
•
The administration of an incorrect dosage;
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•
The administration of study intervention that has undergone temperature excursion from 
the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use.
8.4. Treatment of Overdose
For this study, any dose of study intervention greater than 1 dose of study intervention within 
a 24-hour time period will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator 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 as well as the duration of the overdose in the 
CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
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
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Immunogenicity Assessments
Immunogenicity assessments are described in Section 8.1.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
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8.11. Study Procedures – Maternal Participants
The following procedures apply to both Phase 2 and Phase 3 maternal participants.
8.11.1. Visit 1: Screening (-28 Days to Vaccination 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the maternal participant.  Each 
signature on the ICD must be personally dated by the signatory.  The investigator or his or 
her designee will also sign the ICD.  A copy of the signed 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.
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 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 and tobacco usage.
•
Phase 3 only: For participants who are HIV-infected, record HIV viral load and CD4 
count results from the most recent test performed in the previous 6 months.
•
Obtain and record the LMP and EDD.
•
Measure and record vital signs, including oral temperature, seated blood pressure, and 
heart rate.
•
Perform physical examination including but not limited to weight and height, evaluating 
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.
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•
Perform obstetric examination including but not limited to fetal heart tones and fetal 
movement. Note: Repeat and conduct targeted physical and obstetric examination if it 
was last performed greater than 7 days prior to vaccination.
•
Perform an obstetric ultrasound scan and/or record findings to confirm singleton 
pregnancy and rule out fetal abnormalities.
•
Record nonstudy vaccinations as described in Section 6.5.
•
Collect and record concomitant medication associated with AE/SAEs.
•
Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met.
•
Ensure that the participant meets none of the temporary delay criteria as described in 
Section 5.5.
•
Explain the e-diary technologies available for this study (see Section 8.15) and assist the 
participant in downloading the study application onto her own device or issue a 
provisioned device if required.
•
Record systemic events at baseline in the e-diary.
•
Assign a single participant identifier using the IRT system.
•
Collect a blood sample (approximately 20 mL) for immunogenicity testing.
•
Obtain a nasal (midturbinate) swab (collected by site staff).
•
Obtain the participant’s randomization number and study intervention allocation using 
the IRT system.
•
Unblinded site staff member(s) will dispense/administer 1 dose of study intervention into 
the deltoid muscle of the (preferably) nondominant arm.  Please refer to the IP manual for 
further instruction on this process.
•
Blinded site staff must observe the participant for at least 30 minutes after study 
intervention administration for any acute reactions.  Record any acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of the 
CRF, and on an SAE form as applicable.
•
Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.14).
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•
Issue a measuring device to measure local reactions at the injection site and a 
thermometer for recording daily temperatures and provide instructions on their use.
Provide instructions on e-diary completion and ask the participant to complete the 
reactogenicity e-diary from Day 1 through 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 through 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).
•
Provide instructions on COVID-19 illness e-diary completion and ask the participant to 
complete the COVID-19 illness e-diary at least weekly, if she is diagnosed with 
COVID-19 or has possible new or increased symptoms, or when she receives a reminder.  
See Section 8.15 for further details.
•
Ask the participant to contact the site staff or investigator immediately if she experiences 
any of the following from Day 1 through Day 7 after vaccination (where Day 1 is the day 
of vaccination) to determine if an unscheduled reactogenicity visit or COVID-19 illness 
visit is required:
•
Fever ≥39.0°C (≥102.1°F).
•
Redness or swelling at the injection site measuring greater than 10 cm 
(>20 measuring device units).
•
Severe pain at the injection site.
•
Any severe systemic event.
•
Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
•
Ask the participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if she experiences any respiratory symptoms as 
detailed in Section 8.13.
•
Record AEs and SAEs as described in Section 8.3.
•
Schedule an appointment for the participant to return for the next study visit.
•
Remind the participant to bring the e-diary to the next visit.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the study intervention accountability records.
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•
The investigator or appropriately qualified designee reviews the reactogenicity e-diary 
data online following vaccination to evaluate participant compliance and as part of the 
ongoing safety review. Daily review is optimal during the active diary period.
8.11.1.1. Visit 2 – Vaccination 2 (Clinic: 19-23 Days After Vaccination 1)
If delivery occurs before this visit, this visit will be conducted as soon as possible after 
delivery.  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.
•
Measure vital signs (body temperature, pulse rate, and seated blood pressure).
•
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.
•
Record AEs and SAEs as described in Section 8.3.
•
Review the participant’s reactogenicity e-diary data.  Collect stop dates of any 
reactogenicity e-diary events ongoing on the last day that the reactogenicity e-diary was 
completed and record stop dates in the CRF if required.
•
Record nonstudy vaccinations as described in Section 6.5.
•
Collect and record concomitant medication associated with AE/SAEs.
•
Ensure and document that the participant is still eligible for continued participation.
•
Ensure that the maternal participant meets none of the temporary delay criteria as 
described in Section 5.5.
•
Collect a blood sample (approximately 20 mL) for immunogenicity testing.
Note: blood samples for immunogenicity will be drawn in Phase 2 maternal 
participants only.
•
Obtain a nasal swab (collected by site staff).
•
Unblinded site staff member(s) will dispense/administer 1 dose of study intervention into 
the deltoid muscle of the (preferably) nondominant arm.  Please refer to the IP manual for 
further instruction on this process.
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•
Blinded site staff must observe the participant for at least 30 minutes after study 
intervention administration for any acute reactions.  Record any acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of the 
CRF, and on an SAE form as applicable.
•
Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.14).
•
Ensure the participant remains comfortable with the chosen e-diary platform, confirm
instructions on e-diary completion, and ask the participant to complete the reactogenicity 
e-diary from Day 1 through Day 7, with Day 1 being the day of vaccination.
•
Ask the participant to contact the site staff or investigator immediately if she experiences 
any of the following from Day 1 through Day 7 after vaccination (where Day 1 is the day 
of vaccination) to determine if an unscheduled reactogenicity visit is required:
•
Fever ≥39.0瀽C (≥102.1瀽F).
•
Redness or swelling at the injection site measuring greater than 10 cm 
(>20 measuring device units).
•
Severe pain at the injection site.
•
Any severe systemic event.
•
Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
•
Ask the participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if she experiences any COVID-19 illness
symptoms as detailed in Section 8.13.
•
Schedule an appointment for the participant to return for the next study visit.
•
Remind the participant to bring the e-diary to the next visit.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the study intervention accountability records.
The investigator or appropriately qualified designee reviews the reactogenicity e-diary data 
online following vaccination to evaluate participant compliance and as part of the ongoing 
safety review. Daily review is optimal during the active diary period.
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8.11.1.2. Visit 3 – 2-Week Postvaccination Follow-up (Clinic)
If delivery occurs before this visit, this visit will not be conducted.
•
Phase 3 only: For participants who are HIV-infected, record HIV viral load and CD4 
count results from the most recent test performed since their last visit (if any).
•
Record nonstudy vaccinations as described in Section 6.5.
•
Collect and record concomitant medication associated with AE/SAEs.
•
Review the participant’s reactogenicity e-diary data.  Collect stop dates of any 
reactogenicity e-diary events ongoing on the last day that the reactogenicity e-diary was 
completed and record stop dates in the CRF if required.
•
Ensure and document that the participant is still eligible for continued participation.
•
Collect a blood sample (approximately 20 mL) for immunogenicity testing.
•
Record AEs and SAEs as described in Section 8.3.
•
Ask the participant to contact the site staff or investigator if an emergency room visit or 
hospitalization occurs.
•
Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.14).
•
Ask the participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if she experiences any COVID-19 illness
symptoms as detailed in Section 8.13.
•
Schedule an appointment for the participant to return for the next study visit.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
8.11.1.3. Visit 4 – 1-Month Postvaccination Follow-up Visit (Clinic: 28-35 Days After 
Visit 2)
If delivery occurs before this visit, this visit will not be conducted.
•
Phase 3 only: For participants who are HIV-infected, record HIV viral load and CD4 
count results from the most recent test performed since their last visit (if any).
•
Measure vital signs (body temperature, pulse rate, and seated blood pressure).
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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.
•
Record nonstudy vaccinations as described in Section 6.5.
•
Collect and record concomitant medication associated with an AE.
•
Ensure and document that the participant is still eligible for continued participation. 
Collect a blood sample (approximately 20 mL) for immunogenicity testing.
•
Record AEs and SAEs as described in Section 8.3.
•
Ask the participant to contact the site staff or investigator if an emergency room visit or 
hospitalization occurs.
•
Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.14).
•
Ask the participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if she experiences any COVID-19 illness
symptoms as detailed in Section 8.13.
•
Schedule an appointment for the participant to return for the next study visit.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
8.11.1.4. Visit 5 – Delivery
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.
•
Phase 3 only: For participants who are HIV-infected, record HIV viral load and CD4 
count results from the most recent test performed since their last visit (if any).
•
Record nonstudy vaccinations as described in Section 6.5.
•
Collect and record concomitant medication associated with AE/SAEs.
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•
Ensure and document that the participant is still eligible for continued participation.
•
Collect a blood sample (approximately 20 mL) for immunogenicity testing. If a sample 
for this purpose has already been collected in the previous 7 days (eg, per the procedures 
at Visit 4 for Phase 2/3 participants), a second sample need not be collected.
•
Note: A cord blood sample of approximately 10 mL for immunogenicity assessments
must also be collected. Please refer to Section 8.18.1 for details of the infant delivery 
visit.
•
Record pregnancy outcome information, including vital status of the infant (live,
stillbirth, etc), mode of delivery (vaginal delivery or cesarean delivery), and the use of 
any assisted devices (forceps or vacuum).
•
Record AEs and SAEs as described in Section 8.3.
•
If Visit 5 occurs within 1 month after study vaccination: Ask the participant to contact the 
site staff or investigator if the participant experiences acute chest pain, shortness of 
breath, or palpitations (see Section 8.14).
•
Ask the participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if she experiences any COVID-19 illness
symptoms as detailed in Section 8.13.
•
Schedule a telephone call for the participant’s next study visit.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
8.11.1.5. Visit 6 – 1-Week Postdelivery Follow-up (Telephone Call: 7-10 Days After 
Delivery)
•
Record nonstudy vaccinations as described in Section 6.5.
•
Collect and record concomitant medication associated with AE/SAEs.
•
Ensure and document that the participant is still eligible for continued participation.
•
If not obtained at the time of delivery, update pregnancy outcome information, including 
vital status of the infant (live, stillbirth, etc), mode of delivery (vaginal delivery or 
cesarean delivery), and the use of any assisted devices (forceps or vacuum).
•
Record AEs and SAEs as described in Section 8.3.
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•
If Visit 6 occurs within 1 month after study vaccination: Ask the participant to contact the 
site staff or investigator if the participant experiences acute chest pain, shortness of 
breath, or palpitations (see Section 8.14).
•
Ask the participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if she experiences any COVID-19 illness
symptoms as detailed in Section 8.13.
•
Schedule an appointment for the participant to return for the next study visit.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
8.11.1.6. Visit 7 – 1-Month Postdelivery Follow-up (Clinic: 21 to 35 Days After Delivery)
•
All participants will be unblinded. Maternal participants who received BNT162b2 will 
follow the procedures below and those who received placebo will follow the procedures 
in Section 8.17.
•
Phase 3 only: For participants who are HIV-infected, record HIV viral load and CD4 
count results from the most recent test performed since their last visit (if any).
•
Record nonstudy vaccinations as described in Section 6.5.
•
Collect and record concomitant medication associated with AE/SAEs.
•
Ensure and document that the participant is still eligible for continued participation.
•
Record AEs and SAEs as described in Section 8.3.
•
Ask the participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if she experiences any COVID-19 illness
symptoms as detailed in Section 8.13.
•
Schedule an appointment for the participant to return for the next study visit.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
8.11.1.7. Visit 8 – 6-Month Postdelivery Follow-up (Clinic: 160-200 Days After Delivery)
•
Phase 3 only: For participants who are HIV-infected, record HIV viral load and CD4 
count results from the most recent test performed since their last visit (if any).
•
Record nonstudy vaccinations as described in Section 6.5.
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•
Collect and record concomitant medication associated with AE/SAEs.
•
Collect a blood sample (approximately 20 mL) for immunogenicity testing.
•
Record SAEs as described in Section 8.3.
•
Collect the e-diary or assist the participant to delete the application.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
8.12. Unscheduled Visit for Reactogenicity Events
If a Grade 3 local reaction (Section 8.2.2.2), systemic event (Section 8.2.2.3), or fever 
(≥39.0°C [102.1°F]) (Section 8.2.2.4) is reported in the reactogenicity e-diary, a telephone 
contact should occur to ascertain further details and determine whether a site visit is 
clinically indicated. If suspected Grade 4 local reaction (Section 8.2.2.2), systemic event 
(Section 8.2.2.3), or fever (>40.0°C [>104.0°F]) (Section 8.2.2.4) is reported in the 
reactogenicity e-diary, a telephone contact or site visit should occur to confirm the fever and 
whether the event meets the criteria for Grade 4.
A site visit must be scheduled as soon as possible to assess the participant unless any of the 
following is true:
•
The participant is unable to attend the unscheduled visit.
•
The local reaction/systemic event is no longer present at the time of the telephone 
contact.
•
The participant recorded an incorrect value in the reactogenicity e-diary (confirmation of 
a reactogenicity e-diary data entry error).
•
The PI or authorized designee determined it was not needed.
This telephone contact will be recorded in the participant’s source documentation and the 
CRF.
If the participant is unable to attend the unscheduled visit, or the PI or authorized designee 
determined it was not needed, any ongoing local reactions/systemic events must be assessed 
at the next study visit.
During the unscheduled visit, the reactions should be assessed by the investigator or a 
medically qualified member of the study staff such as a study physician or a study nurse, as 
applicable to the investigator’s local practice, who will:
•
Measure body temperature (°F/°C).
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•
Measure minimum and maximum diameters of redness (if present).
•
Measure minimum and maximum diameters of swelling (if present).
•
Assess injection site pain (if present) in accordance with the grades provided in 
Section 8.2.2.2.
•
Assess systemic events (if present) in accordance with the grades provided in 
Section 8.2.2.3.
•
Assess for other findings associated with the reaction and record on the AE page of the 
CRF, if appropriate.
The investigator or an authorized designee will complete the unscheduled visit assessment 
page of the CRF.
8.13. COVID-19 Surveillance (All Maternal Participants)
If a participant experiences any of the following from the time of vaccination (irrespective of 
perceived etiology or clinical significance), she is instructed to contact the site immediately
and, if confirmed, participate in an in-person or telehealth visit as soon as possible, optimally 
within 3 days after symptom onset (and at the latest 4 days after symptom resolution).
Note that:
•
If new symptoms are reported within 4 days after resolution of all previous symptoms, 
they will be considered as part of a single illness and a second illness visit is not required;
•
Surveillance of potential COVID-19 symptoms should continue even if a participant has 
a positive SARS-CoV-2 test earlier in the study.
During the 7 days following each vaccination, potential COVID-19 symptoms that overlap 
with specific systemic events (ie, fever, chills, new or increased muscle pain, diarrhea, 
vomiting) should not trigger a potential COVID-19 illness visit unless, in the investigator’s 
opinion, the clinical picture is more indicative of a possible COVID-19 illness than vaccine 
reactogenicity.
If, in the investigator’s opinion, the symptoms are considered more likely to be vaccine 
reactogenicity, but a participant is required to demonstrate that they are 
SARS-CoV-2–negative, a local SARS-CoV-2 test may be performed: if positive, the 
symptoms should be recorded as a potential COVID-19 illness; if not, the symptoms should 
be recorded as AEs (unless already captured in the reactogenicity e-diary).
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Maternal participants may utilize a COVID-19 illness e-diary through an application 
(see Section 8.15) installed on a provisioned device or on the participant’s own personal 
device to prompt her to report any symptoms.  Note that this does not substitute for a 
participant’s routine medical care.  Therefore, participants should be encouraged to seek care, 
if appropriate, from their usual provider.
•
A diagnosis of COVID-19;
•
Fever;
•
New or increased cough; 
•
New or increased shortness of breath; 
•
Chills; 
•
New or increased muscle pain; 
•
New loss of taste/smell;
•
Sore throat;
•
Diarrhea;
•
Vomiting.
8.13.1. Potential Maternal COVID-19 Illness Visit (Optimally Within 3 Days After 
Potential COVID-19 Illness Onset)
This visit may be conducted as an in-person or telehealth visit; a telehealth visit involves the 
sharing of healthcare information and services via telecommunication technologies 
(eg, audio, video, videoconferencing software) remotely, thus allowing the participant and 
investigator to communicate on aspects of clinical care.
As a participant’s COVID-19 illness may evolve over time, several contacts may be required 
to obtain the following information:
•
Record AEs, as appropriate as described in Section 8.3.  Note: Potential COVID-19 
illnesses that are consistent with the clinical endpoint definition should not be recorded as 
AEs. These data will be captured as efficacy assessment data only on the relevant pages 
of the CRF, as these are expected endpoints.
•
Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for her clinical care.
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•
If the visit is conducted in person, obtain a nasal (midturbinate) swab (collected by site 
staff).  Alternatively, if conducted by telehealth, instruct the participant to self-collect a 
nasal (midturbinate) swab and ship for assessment at the central laboratory.
•
Collect COVID-19–related standard-of-care clinical and laboratory information. 
This includes, but is not limited to:
•
Symptoms and signs, including:
•
Clinical signs at rest indicative of severe systemic illness (RR ≥30 breaths/min, 
HR ≥125 beats/min, SpO2 ≤93% on room air at sea level, or PaO2/FiO2 <300 mm Hg)
•
Evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors)
•
Significant acute renal, hepatic, or neurologic dysfunction
•
Respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, 
mechanical ventilation, or ECMO)
•
Clinical diagnosis
•
Local laboratory SARS-CoV-2 test result(s) 
Note that if it is routine practice to perform a repeat local SARS-CoV-2 test for any 
reason, then a repeat nasal (midturbinate) swab should also be obtained and shipped 
for assessment at the central laboratory.
•
Full blood count
•
Blood chemistry, specifically creatinine, urea, LFTs, and CRP
•
Imaging results (eg, CT or MRI scan) to document neurologic dysfunction
•
Hospitalization
•
Admission to the ICU
•
Death
•
Schedule an appointment for the participant to return for the potential COVID-19 
convalescent visit once she has recovered.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
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8.13.2. Potential Maternal COVID-19 Convalescent Visit (28 to 35 Days After Potential 
COVID-19 Illness Visit)
•
Record AEs, as appropriate as described in Section 8.3.  Note: Potential COVID-19 
illnesses that are consistent with the clinical endpoint definition should not be recorded 
as AEs. These data will be captured as efficacy assessment data only on the relevant 
pages of the CRF, as these are expected endpoints.
•
Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for her clinical care.
•
Collect a blood sample (approximately 20 mL) for immunogenicity testing.
•
Collect/update COVID-19–related clinical and laboratory information (detailed in 
Section 8.13.1).
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
•
Record any AEs that occur within the 48 hours after the blood draw as described in 
Section 8.3.
8.14. Additional Procedures for Monitoring of Potential Myocarditis or Pericarditis
Any study participant who reports acute chest pain, shortness of breath, palpitations, or any 
other symptom(s) that might be indicative of myocarditis or pericarditis within 4 weeks after 
a study vaccination should be specifically evaluated, preferably by a cardiologist, for possible 
myocarditis or pericarditis.
In addition to a clinical evaluation, the following should be performed:
•
ECG and
•
Measurement of the troponin level
If myocarditis or pericarditis is suspected based upon the initial evaluation, the following 
should also be performed:
•
Cardiac echocardiogram and/or
•
Cardiac magnetic resonance study
Details of the symptoms reported, and results of the investigations performed, will be 
recorded in the CRF.
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8.15. Communication and Use of Technology
In a study of this nature that requires illness events to be reported outside of scheduled study 
visits, it is vital that communication between the study site and the maternal participant is 
maintained to ensure that endpoint events are not missed for her or her infant.  This study 
will employ various methods, tailored to the individual participant, to ensure that 
communication is maintained and study information can be transmitted securely.  Using 
appropriate technology, such as a study application, a communication pathway between the 
participant and the study site staff will be established.  The participant may be able to utilize 
her 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, including the ability of the participant to report whether or 
not the participant has experienced symptoms that could represent a potential COVID-19 
illness (COVID-19 illness e-diary; see Section 8.13).
•
An alert in the event that the participant is hospitalized.
•
Visit reminders.
•
Messages of thanks and encouragement from the study team.
•
A platform for recording local reactions and systemic events (reactogenicity e-diary) –
see Section 8.2.2.
If a maternal participant is not actively completing either the reactogenicity or COVID-19 
illness e-diary, the investigator or designee is required to contact the participant to ascertain
why and also to obtain details of any missed events.
8.16. SARS-CoV-2 NAAT Results From Visits 1 and 2 and Potential COVID-19 Illness 
Visits
Nasal (midturbinate) swabs for SARS-CoV-2 NAAT are obtained at:
•
Visits 1 and 2: To determine whether a participant will be included in efficacy analyses 
of those with no serological or virological evidence (up to 7 days after receipt of the 
second dose) of past SARS-CoV-2 infection.
•
Potential COVID-19 illness visits: To determine whether symptoms experienced by the 
participant fulfill the COVID-19 case definition.
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Research laboratory–generated positive results from the Visit 1 and Visit 2 swabs, and all 
results from the illness visit swabs, will be provided to the site once available, but this will 
not be in real time and cannot be relied upon to direct clinical care.  Therefore, the participant 
should be directed to seek additional testing through her primary healthcare providers at a 
licensed clinical laboratory when exhibiting potential COVID-19 symptoms or otherwise 
receiving a positive result and counseled on whether to take any precautionary measures 
pending confirmatory testing.
Participants who have a positive SARS-CoV-2 NAAT result prior to Visit 2 should be 
handled as follows:
•
Positive SARS-CoV-2 test with no symptoms, either at Visit 1 or any time between 
Visit 1 and Visit 2: A positive test in an asymptomatic participant does not meet 
exclusion criterion 2; therefore, Vaccination 2 should proceed as normal.
•
Confirmed COVID-19 (ie, symptoms and positive SARS-CoV-2 test) diagnosed at 
Visit 1 or any time between Visit 1 and Visit 2 does not meet exclusion criterion 2; 
therefore, Vaccination 2 should proceed as normal.
8.17. Procedures for Administration of BNT162b2 to Those Originally Assigned to 
Placebo
Maternal participants will be given BNT162b2 at the 1-month postdelivery visit, and will 
follow the procedures listed in this section for the remainder of their participation in the 
study.
8.17.1. Visit 101 – Vaccination 3 – 1-Month Postdelivery Follow-up (Clinic: 21 to 
35 Days After Delivery)
•
Confirm that the participant originally received only placebo at Vaccination 1/2.  
Secondary confirmation by another site staff member is required.
•
Before vaccination and before any study-related procedures are performed: Review and 
consider inclusion criteria 2, 5, and 11 and exclusion criteria 1, 3, 4, 5, 9, 13, 14, 15, and 
17 prior to vaccination. If, in the investigator’s judgment, vaccination is in the best 
interests of the participant, vaccination may proceed, even if inclusion criteria are not met 
and exclusion criteria are met. Such exceptions should be recorded in the participant’s 
source documents.
•
Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for her clinical care.
•
Ensure that the participant meets none of the temporary delay criteria as described in 
Section 5.5.
•
Record AEs as described in Section 8.3.
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•
Collect a blood sample (approximately 20 mL) for immunogenicity testing.
•
Obtain a nasal (midturbinate) swab (collected by site staff).
•
Obtain the participant’s vaccine vial allocation using the IRT system.
•
Site staff member(s) will dispense/administer 1 dose of BNT162b2 into the deltoid 
muscle of the (preferably) nondominant arm.
•
Site staff must observe the participant for at least 30 minutes after BNT162b2 
administration for any acute reactions.  Record any acute reactions (including time of 
onset) in the participant’s source documents and on the AE page of the CRF, and on an 
SAE form as applicable.
•
Ask the participant to contact the site staff or investigator if the participant experiences
acute chest pain, shortness of breath, or palpitations (see Section 8.14).
•
Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
•
Schedule an appointment for the participant to return for the next study visit.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs and the 
dispenser/administrator updates the study intervention accountability records.
8.17.2. Visit 102 – Vaccination 4 (19 to 23 Days After Visit 101)
It is anticipated that the procedures below will be conducted in a stepwise manner.
•
Record AEs as described in Section 8.3.
•
Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for her clinical care.
•
Before vaccination and before any study-related procedures are performed: Review and 
consider inclusion criteria 2, 5, and 11 and exclusion criteria 1, 3, 4, 5, 9, 13, 14, 15,
and 17 prior to vaccination.  If, in the investigator’s judgment, vaccination is in the best 
interests of the participant, vaccination may proceed, even if inclusion criteria are not met 
and exclusion criteria are met. Such exceptions should be recorded in the participant’s 
source documents.
•
Ensure that the participant meets none of the temporary delay criteria as described in 
Section 5.5.
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•
Obtain a nasal (midturbinate) swab (collected by site staff).
•
Obtain the participant’s vaccine vial allocation using the IRT system.
•
Site staff member(s) will dispense/administer 1 dose of study intervention into the deltoid 
muscle of the (preferably) nondominant arm.  Please refer to the IP manual for further 
instruction on this process.
•
Site staff must observe the participant for at least 30 minutes after study intervention 
administration for any acute reactions.  Record any acute reactions (including time of 
onset) in the participant’s source documents and on the AE page of the CRF, and on an 
SAE form as applicable.
•
Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.14).
•
Ask the participant to contact the site staff or investigator if a medically attended event
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
•
Schedule an appointment to call the participant by telephone for the next study contact.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs and the 
dispenser/administrator updates the study intervention accountability records.
8.17.3. Visit 103 – 1-Month Follow-up Telephone Contact (After Vaccination 4) (28 to 
35 Days After Visit 102)
•
Contact the participant by telephone.
•
Record AEs as described in Section 8.3.
•
Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for her clinical care.
•
Phase 3 only: For participants who are HIV-infected, record HIV viral load and CD4 
count results from the most recent test performed since Visit 101 (if any).
•
Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
•
Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.14).
•
Complete the source documents.
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•
The investigator or an authorized designee completes the CRFs.
8.18. Study Procedures – Infant Participants
8.18.1. Infant Participants: Visit 1 – Delivery
•
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 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.
•
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.
•
Collect and record concomitant medication associated with AE/SAEs.
•
Ensure and document that the infant is eligible.
•
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.
•
If cord blood is unavailable, a blood sample may be collected from the infant participant 
preferably within 72 hours.  The volume of blood collected will be based on the weight of 
the infant (refer to Table 1).
•
Record AEs, SAEs, and AESIs as described in Section 8.3.
•
Schedule an appointment for the participant for the next study visit.
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•
Ask the maternal participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if the infant participant experiences any 
COVID-19 illness symptoms as detailed in Section 8.19.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
8.18.2. Visit 2 – 1-Week Postdelivery Follow-up (Telephone Call: 7-10 Days After 
Visit 1)
•
Ensure and document that the infant is still eligible.
•
Record breastfeeding information.
•
Collect and record concomitant medication associated with AE/SAEs.
•
Record AEs, SAEs, and AESIs as described in Section 8.3.
•
Schedule an appointment for the participant to return for the next study visit.
•
Ask the maternal participant to contact the site staff or investigator (this could be via the 
COVID-19 illness e-diary) immediately if the infant participant experiences any 
COVID-19 illness symptoms as detailed in Section 8.19.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
8.18.3. Visit 3 – 6-Months-of-Age Follow-up (Clinic: 160-200 Days After Visit 1)
•
Record concomitant medication associated with SAEs.
•
Record breastfeeding information.
•
Collect a blood sample (approximately 5 mL) for immunogenicity testing.  The volume 
of blood collected will be based on the weight of the infant (refer to Table 1).
•
Record AEs, SAEs, and AESIs as described in Section 8.3.
•
Collect e-diary or assist the maternal participant to delete application.
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
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8.19. COVID-19 Surveillance (All Infant Participants)
If an infant participant experiences any of the following (irrespective of perceived etiology or 
clinical significance), the maternal participant is instructed to contact the site immediately 
and, if confirmed, participate in an in-person or telehealth visit as soon as possible, optimally 
within 3 days after symptom onset (and at the latest 4 days after symptom resolution). 
Note that this does not substitute for an infant participant’s routine medical care.  Therefore, 
maternal participants should be encouraged to seek care, if appropriate, from their infant’s 
usual provider.
Additionally:
•
If new symptoms are reported within 4 days after resolution of all previous symptoms, 
they will be considered as part of a single illness and a second illness visit is not required;
•
Surveillance of potential COVID-19 symptoms should continue even if a participant has 
a positive SARS-CoV-2 test earlier in the study.
Signs and symptoms of an acute respiratory illness in the infant will not be considered a 
potential COVID-19–related illness if they occur within the first 72 hours after birth and 
should not trigger an illness visit.
•
A diagnosis of COVID-19;
•
Fever; 
•
New or increased cough; 
•
New or increased shortness of breath;
•
Diarrhea;
•
Vomiting.
8.19.1. Potential Infant COVID-19/MIS-C Illness Visit (Optimally Within 3 Days After 
Potential COVID-19 Illness Onset)
This visit may be conducted as an in-person or telehealth visit; a telehealth visit involves the 
sharing of healthcare information and services via telecommunication technologies 
(eg, audio, video, videoconferencing software) remotely, thus allowing the parent and 
investigator to communicate on aspects of the infant’s clinical care.
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As a participant’s COVID-19 illness may evolve over time, several contacts may be required 
to obtain the following information:
•
Record AEs, as appropriate as described in Section 8.3.  Note: Potential COVID-19 
illnesses that are consistent with the clinical endpoint definition should not be recorded as 
AEs. These data will be captured as efficacy assessment data only on the relevant pages 
of the CRF, as these are expected endpoints.
•
Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for his/her clinical care.
•
If the visit is conducted in person, obtain a nasal swab (collected by site staff).  
Alternatively, if conducted by telehealth, instruct the maternal participant to collect a 
nasal swab from the infant and ship for assessment at the central laboratory.
•
Collect COVID-19–related standard-of-care clinical and laboratory information.  This 
includes, but is not limited to:
•
Clinical signs at rest indicative of severe systemic illness:
•
RR (breaths/min): >50 in birth to 1 week of age, ≥40 in 1 week to 1 month of age,
≥34 in 1 month to 6 months of age;
•
HR (beats/min): >180;
•
SpO2 ≤92% on room air or >50% FiO2 to maintain ≥92% or PaO2/FiO2 <300 mm 
Hg;
•
Respiratory failure (defined as needing high-flow oxygen including nasal 
CPaP/BiPaP, noninvasive ventilation, mechanical ventilation, or ECMO);
•
Evidence of shock or cardiac failure;
•
SBP (mm Hg):
•
<65 from birth to 1 week of age, <75 from 1 week to 1 month of age, <100 from 
1 month to 6 months of age;
OR 
•
Requiring vasoactive drugs to maintain BP in the normal range;
•
Significant acute renal failure: serum creatinine >2 times ULN for age or 2-fold 
increase in baseline creatinine;
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•
Significant GI/hepatic failure: total bilirubin >4 mg/dL or ALT 2 times ULN for 
age; 
•
Significant neurologic dysfunction: Glasgow Coma Scale score <11 or acute 
change in mental status with a decrease in Glasgow Coma Scale score ≥3 points 
from abnormal baseline;
•
Admission to an ICU;
•
Death;
•
Clinical diagnosis;
•
Local laboratory SARS-CoV-2 test result(s).  Note that if it is routine practice to 
perform a repeat local SARS-CoV-2 test for any reason, then a repeat nasal swab 
should also be obtained and shipped for assessment at the central laboratory.
•
Full blood count, blood chemistry, specifically creatinine, urea, liver function 
tests, and CRP, ESR, fibrinogen, procalcitonin, D-dimer, ferritin, LDH, or 
IL-6 if available.
•
Number and type of any healthcare contact; duration of hospitalization and ICU stay.
8.19.2. Potential Infant COVID-19 Convalescent Visit (28 to 35 Days After Potential 
COVID-19 Illness Visit)
•
Record AEs, as appropriate as described in Section 8.3.  Note: Potential COVID-19 
illnesses that are consistent with the clinical endpoint definition should not be recorded as 
AEs. These data will be captured as efficacy assessment data only on the relevant pages 
of the CRF, as these are expected endpoints.
•
Record details of any of the prohibited medications specified in Section 6.5.1 received by 
the participant if required for her clinical care.
•
Collect a blood sample (up to 5 mL based on weight [Table 1]) for immunogenicity 
testing.
•
Collect/update COVID-19–related clinical and laboratory information (detailed in 
Section 8.13.1).
•
Complete the source documents.
•
The investigator or an authorized designee completes the CRFs.
•
Record any AEs that occur within the 48 hours after the blood draw as described in 
Section 8.3.
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9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in a 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
9.1.1. Estimands
The estimands corresponding to each primary, secondary, and exploratory objective are 
described in the table in Section 3.
In the primary safety objective evaluations, missing reactogenicity e-diary data will not be 
imputed. Missing AE start dates will be imputed according to Pfizer safety rules. No other 
missing information will be imputed in the safety analysis.
The estimands to evaluate the immunogenicity objectives are based on the evaluable 
immunogenicity populations (Section 9.3). These estimands estimate the vaccine effect in 
the hypothetical settings where participants follow the study schedules and protocol 
requirements as directed. Missing antibody results will not be imputed. Immunogenicity 
results that are below the LLOQ will be set to 0.5 × LLOQ in the analysis; this may be 
adjusted once additional data on the assay characteristics become available.
The estimands to evaluate the efficacy objectives are based on the evaluable efficacy 
populations (Section 9.3).  These estimands estimate the vaccine effect in the hypothetical 
setting where participants follow the study schedules and protocol requirements as directed.  
In addition, VE will also be analyzed by the all-available efficacy (mITT) populations. 
Missing laboratory results will not be imputed.
9.1.2. Statistical Hypotheses
Due to early enrollment termination and reduced sample size, all endpoints will be analyzed
descriptively without formal hypothesis tests.
9.2. Sample Size Determination
The sample size for the Phase 2 portion of the study and for the entire study is not driven by
statistical hypothesis testing.
For safety outcomes, Table 5 shows the probability of observing at least 1 AE for a given 
true event rate of a particular AE, for various sample sizes. For example, if the true AE rate 
is 2%, with 100 participants in a vaccine group, there is 95% probability of observing at 
least 1 AE in Phase 2. If the true AE rate is 1%, with 175 participants in a vaccine group, 
there is 83% probability of observing at least 1 AE in Phase 3.
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Table 5.
Probability of Observing at Least 1 AE by Assumed True Event Rates 
With Different Sample Sizes
Assumed True Event Rate of an 
AE
N=100
N=175
0.1%
0.10
0.16
0.3%
0.26
0.41
0.5%
0.39
0.58
0.8%
0.55
0.75
1.0%
0.63
0.83
2.0%
0.87
0.97
3.0%
0.95
>0.99
Note: N = number of participants in a vaccine group.
9.3. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Population
Description
Enrolled
All participants who have a signed ICD.
Randomized
All participants who are assigned a randomization number in the IWR 
system.
Evaluable immunogenicity
(maternal)
All eligible randomized participants who receive 2 doses of the vaccine 
to which they are randomized with Dose 2 received within the predefined 
window, have at least 1 valid and determinate immunogenicity result 
from the blood sample collected within an appropriate window, and have 
no other important protocol deviations as determined by the clinician.
Dose 1 evaluable immunogenicity 
(maternal)
All eligible randomized participants who receive Dose 1 of the vaccine to 
which they are randomized, have at least 1 valid and determinate 
immunogenicity result from the blood sample collected after Dose 1 and 
before Dose 2, and have no other important protocol deviations before 
Dose 2 as determined by the clinician.
Evaluable immunogenicity (infant) All infant participants born to evaluable immunogenicity maternal 
participants and have no important protocol deviations as determined by 
the clinician.
All-available immunogenicity
(maternal)
All participants who receive at least 1 dose of the study intervention with 
at least 1 valid and determinate immunogenicity result after vaccination.
All-available immunogenicity 
(infant)
All infant participants born to all-available immunogenicity maternal 
participants.
Evaluable efficacy (maternal)
All eligible randomized participants who receive all vaccination(s) as 
randomized within the predefined window and have no other important 
protocol deviations as determined by the clinician.
All-available efficacy (mITT) 
(maternal)
Dose 1 all-available efficacy: All randomized participants who receive at 
least 1 vaccination.
Dose 2 all-available efficacy: All randomized participants who complete 
2 vaccination doses.
All-available efficacy (mITT) 
(infant)
All infant participants born to Dose 1 all-available maternal participants.
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Population
Description
Safety (maternal)
All randomized participants who receive at least 1 dose of the study 
intervention.
Safety (infant)
All infant participants born to maternal participants who receive at least 
1 dose of the study intervention.
9.4. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe 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 and secondary 
endpoints.
9.4.1. General Considerations
CIs for all endpoints in the statistical analysis will be presented as 2-sided at the 95% level 
unless specified otherwise.
The safety analyses are based on the safety populations.  Participants will be summarized by 
vaccine group according to the study intervention they (or their mothers) actually received.  
Missing reactogenicity e-diary data will not be imputed; missing AE dates will be handled 
according to the Pfizer safety rules.
For all the immunogenicity endpoints, the analysis will be based on the evaluable 
immunogenicity populations. An additional analysis may be performed based on the 
all-available immunogenicity populations if there is a large enough difference in sample size 
between the all-available immunogenicity populations and the evaluable immunogenicity 
populations.  Participants will be summarized according to the vaccine group to which they 
(or their mothers) were randomized.  Missing serology data will not be imputed.
9.4.1.1. Analyses for Binary Data
Descriptive statistics for categorical variables (eg, proportions) are the percentage (%), the 
numerator (n) and the denominator (N) used in the percentage calculation, and the 95% CIs 
where applicable.
The exact 95% CI for binary endpoints for each group will be computed using the 
F distribution (Clopper-Pearson). The 95% CI for the between-group difference for binary 
endpoints will be calculated using the Miettinen and Nurminen method.
The 3-tier approach will be used to summarize AEs.  For both Tier 1 (if any are identified 
during the study) and Tier 2 events, a 95% CI for the between-group difference in 
proportions will be calculated based on the Miettinen and Nurminen method.  In addition, for 
Tier 1 events (if any), the asymptotic p-values will also be presented for the difference in 
proportions, based on the same test statistic and under the assumption that the test statistic is 
asymptotically normally distributed.  For Tier 3 events, counts and percentages for each 
vaccine group will be provided.
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9.4.1.2. Analyses for Continuous Data
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
standard deviation, minimum, and maximum.
9.4.1.2.1. Geometric Means
The geometric means will be calculated as the mean of the assay results after making the 
logarithm transformation and then exponentiating the mean to express results on the original 
scale.  Two-sided 95% CIs will be obtained by taking log transforms of assay results, 
calculating the 95% CI with reference to Student’s t-distribution, and then exponentiating the 
confidence limits.
9.4.1.2.2. Geometric Mean Fold Rises
GMFRs are defined as ratios of the results after vaccination to the results before vaccination.  
GMFRs are limited to participants with nonmissing values at both time points.
GMFRs will be calculated as the mean of the difference of logarithmically transformed 
neutralization titers or antibody levels (later time point minus earlier time point) and 
exponentiating the mean.  The associated 2-sided 95% CIs are obtained by constructing CIs 
using Student’s t-distribution for the mean difference on the logarithm scale and 
exponentiating the confidence limits.
9.4.1.2.3. Geometric Mean Ratios
The GMR will be calculated as the mean of the difference of logarithmically transformed 
assay results (eg, SARS-CoV-2 neutralizing titers in pregnant women minus that in 
nonpregnant women) and exponentiating the mean.  Two-sided CIs will be obtained by 
calculating CIs using Student’s t-distribution for the mean difference of the logarithmically 
transformed assay results and exponentiating the confidence limits.
9.4.1.2.4. Reverse Cumulative Distribution Curves
Empirical RCDCs will plot proportions of participants with values equal to or exceeding a 
specified assay value versus the indicated assay value, for all observed assay values.  Data 
points will be joined by a step function with data points on the left side of the step.
9.4.2. Primary Endpoint(s)
Endpoint
Statistical Analysis Methods
Safety (maternal
participants)
Descriptive statistics will be provided for each reactogenicity endpoint for each dose 
and vaccine group.  Local reactions and systemic events from Day 1 through Day 7 
after each vaccination (where Day 1 is the day of vaccination) will be presented by 
severity and cumulatively across severity levels.  Descriptive summary statistics will 
include counts and percentages of participants with the indicated endpoint and the 
associated Clopper-Pearson 95% CIs (see Section 9.4.1.1).
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Endpoint
Statistical Analysis Methods
AEs will be categorized according to MedDRA terms.  Counts, percentages, and the 
associated Clopper-Pearson 95% CIs of AEs from Dose 1 to 1 month after Dose 2 
will be provided for each vaccine group. A 3-tier approach will be used to summarize 
AEs in Phase 2/3. Under this approach AEs are classified into 1 of 3 tiers: (1) Tier 1 
events are prespecified events of clinical importance and are identified in a list in the 
product’s safety review plan; (2) Tier 2 events are those that are not Tier 1 but are 
considered “relatively common”; a MedDRA preferred term is defined as a Tier 2 
event if there are at least 1% of participants in at least 1 vaccine group reporting the 
event; and (3) Tier 3 events are those that are neither Tier 1 nor Tier 2 events. 
Analysis methods are described in Section 9.4.1.1.
SAEs will be categorized according to MedDRA terms.  Counts, percentages, and the 
associated Clopper-Pearson 95% CIs of SAEs from Dose 1 through 1 month after 
delivery will be provided for each vaccine group.
AEs and SAEs reported for maternal participants during the open-label follow-up 
period will be summarized separately.
Immunogenicity in 
participants without 
evidence of prior 
SARS-CoV-2 
infection (maternal
participants)
GMR, estimated by the ratio of the geometric mean of SARS-CoV-2 neutralizing 
titers in pregnant women to nonpregnant women 1 month after Dose 2 will be 
provided along with associated 2-sided 95% CIs (see Section 9.4.1.2.3). Only 
participants with no serological or virological evidence (up to 1 month after receipt of 
the second dose) of past SARS-CoV-2 infection will be included in the analysis.
The nonpregnant women will be randomly selected from the female participants from 
study C4591001 in the same age group as the pregnant women.
Immunogenicity in 
participants with and 
without evidence of 
prior SARS-CoV-2 
infection (maternal
participants)
This endpoint will be analyzed the same way as for the participants without evidence 
of infection.
9.4.3. Secondary Endpoint(s)
Endpoint
Statistical Analysis Methods
Vaccine efficacy
Ratio of confirmed COVID-19 illness from 7 days after Dose 2 through 1 month 
after delivery per 1000 person-years of blinded follow-up in participants without 
evidence of infection (prior to 7 days after receipt of Dose 2) for the active 
vaccine group to the placebo group 
VE will be estimated by 100 × (1 - IRR), where IRR is the calculated ratio of first
confirmed COVID-19 illness per 1000 person-years of blinded follow-up in the active 
vaccine group to the corresponding illness rate in the placebo group from 7 days after 
Dose 2. The 2-sided 95% CI for VE will be derived using the Clopper-Pearson 
method.
Ratio of confirmed COVID-19 illness from 7 days after Dose 2 through 1 month 
after delivery per 1000 person-years of blinded follow-up in maternal 
participants with and without evidence of infection (prior to 7 days after receipt 
of Dose 2) for the active vaccine group to the placebo group
The same analysis method used for the first VE endpoint will be applied.
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Endpoint
Statistical Analysis Methods
Ratio of incidence of asymptomatic infection of SARS-CoV-2 in evaluable 
participants without evidence of prior SARS-CoV-2 infection for the active 
vaccine group to the placebo group
VE will be estimated by 100 × (1 - IRR), where IRR is the calculated ratio of 
asymptomatic infection in the active vaccine group to the corresponding infection in 
the placebo group. The 2-sided 95% CI for VE will be provided using the 
Clopper-Pearson method.
The analyses will be based on the evaluable efficacy population and the all-available 
efficacy population. Missing efficacy data will not be imputed.
Immunogenicity 
(maternal participants)
GMTs/GMCs of SARS-CoV-2 neutralizing titers and full-length S-binding IgG 
levels at baseline, 2 weeks after Dose 2, 1 month after Dose 2, and 6 months after 
delivery
For SARS-CoV-2 neutralizing titers and full-length S-binding IgG levels,
GMTs/GMCs and 2-sided 95% CIs will be provided for each vaccine group before 
vaccination and at each subsequent time point after vaccination. Statistical methods 
are described in Section 9.4.1.2.1.
Empirical RCDCs will be provided for SARS-CoV-2 neutralizing titers 
(Section 9.4.1.2.4).
GMFRs of SARS-CoV-2 neutralizing titers and full-length S-binding IgG levels
from before vaccination through 2 weeks after Dose 2, 1 month after Dose 2, and 
6 months after delivery
For SARS-CoV-2 neutralizing titers and full-length S-binding IgG levels, the GMFRs 
and 2-sided 95% CIs will be provided for each vaccine group from before vaccination 
to each subsequent time point after vaccination.
GMFRs will be limited to participants with nonmissing values prior to the first dose 
and at the postvaccination time point.  The statistical methods are described in 
Section 9.4.1.2.2.
Safety (infant
participants)
Counts, percentages, and the associated Clopper-Pearson 95% CIs for infant 
participants with specific birth outcomes, AEs from birth through 1 month of age, and 
SAEs and AESIs through 6 months of age will be provided by vaccine group 
according to the study intervention the maternal participants received. A 3-tier 
approach will be used to summarize AEs.
Immunogenicity 
(infant participants)
GMCs at birth and 6 months after delivery, and GMFRs for full-length S-binding IgG 
levels, will be summarized for infant participants using the same statistical analysis 
method described for the secondary immunogenicity endpoints for maternal 
participants.
9.4.4. Exploratory Endpoint(s)
Endpoint
Statistical Analysis Methods
COVID-19 incidence rate 
(maternal participants)
Incidence rate (per 1000 person-years of follow-up) and 2-sided 95% CI for 
confirmed COVID-19 illness from 7 days after the second dose of BNT162b2 will 
be provided for participants who received BNT162b2 at initial randomization.
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Endpoint
Statistical Analysis Methods
Asymptomatic 
SARS-CoV-2 infection 
(maternal participants)
Incidence rate (per 1000 person-years of follow-up) and 2-sided 95% CI for 
asymptomatic SARS-CoV-2 infection based on the N-binding antibody 
seroconversion for participants who received BNT162b2 at initial randomization
and have no serological or virological evidence of prior SARS-CoV-2 infection.
Serological responses by 
COVID-19 and 
SARS-CoV-2 infection 
status (maternal 
participants)
In each subset of participants with confirmed COVID-19, confirmed severe 
COVID-19, and SARS-CoV-2 infection without confirmed COVID-19, 
GMTs/GMCs and GMFRs of SARS-CoV-2 neutralizing titers and full-length 
S-binding IgG levels will be summarized using the same statistical analysis 
method described for the secondary immunogenicity endpoints (maternal).
Immunogenicity from 
baseline to before Dose 2
(Phase 2 maternal 
participants)
In maternal participants enrolled in the Phase 2 portion of the study, GMTs/GMCs
and GMFRs of SARS-CoV-2 neutralizing titers and full-length S-binding IgG 
levels at baseline and before Dose 2 will be summarized using the same statistical 
analysis method described for the secondary immunogenicity endpoints
(maternal).
Immunogenicity (infant
participants by 
breastfeeding status)
For infants breastfed and not breastfed, respectively, GMCs at birth and 6 months 
after delivery, and GMFRs for full-length S-binding IgG levels, will be 
summarized using the same statistical analysis method described for the
secondary immunogenicity endpoints for maternal participants.
Safety (infant participants
by breastfeeding status)
For infants breastfed and not breastfed, respectively, counts, percentages, and the 
associated Clopper-Pearson 95% CIs for infant participants with AEs from birth 
through 1 month of age, and SAEs and AESIs through 6 months of age, will be 
provided by vaccine group according to the study intervention the maternal 
participants received.
COVID-19 incidence rate 
(infant participants)
Counts, incidence of COVID-19 per 1000 person-years of follow-up, and the 
associated 2-sided 95% CIs will be provided for each vaccine group in the infants 
participants.
MIS-C cases (infant 
participants)
Counts, incidence of MIS-C per 1000 person-years of follow-up, and the 
associated 2-sided 95% CIs will be provided for each vaccine group in the infants 
participants.
9.5. Interim Analyses
No formal interim analysis will be conducted for this study. Statistical analyses will be 
carried out when the final data for specified objectives are available while the study is 
ongoing. The timing of these planned analysis and reporting events is described in the 
section below.
9.5.1. Analysis Timing
Statistical analyses will be carried out when the following data are available:
•
Immunogenicity data through 1 month after Dose 2 from all randomized maternal 
participants for assessment of SARS-CoV-2 neutralizing titers.
•
Complete safety and immunogenicity analysis after complete data are available or at the 
end of the study.
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Additional analyses may be conducted if required for regulatory purposes. All analyses 
conducted while the study is ongoing will be performed by an unblinded statistical team.
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will use an IRC, a DMC, and a group of internal case reviewers.  The IRC is
independent of the study team and includes only internal members.  The DMC is independent 
of the study team and includes only external members. The IRC and DMC charters describe 
the role of the IRC and DMC in more detail.
The DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter.  The recommendations made by the DMC to alter the conduct 
of the study will be forwarded to the appropriate Pfizer personnel for final decision.  Pfizer 
will forward such decisions, which may include summaries of aggregate analyses of safety 
data, 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 CIOMS International Ethical Guidelines;
•
Applicable ICH GCP guidelines;
•
Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), 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 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 study 
intervention, 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.
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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 
participant and answer all questions regarding the study.  The participant should be given 
sufficient time and opportunity to ask questions and to decide whether or not to participate in 
the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, 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 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 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 her 
right to access and correct her personal data and to withdraw consent for the processing of 
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 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 are required to sign a new ICD.
Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research.  The optional 
additional research does not require the collection of any further samples. The investigator 
or authorized designee will explain to each participant the objectives of the additional 
research. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period.
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 will 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 participants 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 her actual identity and medical record identification. 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 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 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
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (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 corresponding study results are 
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 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 contributes 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.
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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.
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.
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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 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 clinical monitoring plan.
Description of the use of computerized system is documented in the Data Management Plan.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
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 sponsor 
or designee if requested to do so by the responsible IRB/EC or if such termination is required 
to protect the health of study participants.
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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.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
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 the 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.
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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 at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention
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, 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, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE:
•
Is associated with accompanying symptoms;
•
Requires additional diagnostic testing or medical/surgical intervention;
•
Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.
•
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.
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•
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.
•
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. 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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10.2.3. 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 study 
intervention 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 study intervention caused the 
event, then the event will be handled as “related to study intervention” 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 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.
10.2.4. 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.
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•
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 DILI.  
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are an “adaptor” or are “susceptible.”
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.
Studies that include more detailed hepatic safety assessments (eg, an external hepatic expert 
panel or DMC that has separate definitions and charter) will still need to follow the reporting 
guidelines described below for applicable cases.
In the majority of DILI cases, elevations in AST and/or ALT precede 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 Hepatic 
Injury Council (HIC) should be informed if such a situation occurs during the study; the HIC 
will provide the necessary support to the study team.
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.  For oncology studies, the 
possibility of hepatic neoplasia (primary or secondary) should be considered.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, CK, direct and indirect 
bilirubin, GGT, PT/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/paracetamol (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 samples for acetaminophen/paracetamol 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: Criteria for Allowing Inclusion of Participants With Chronic Stable 
HIV, HCV, or HBV Infection
Potential participants with chronic stable HIV, HCV, or HBV infection may be considered 
for inclusion if they fulfill the following respective criteria.
Known HIV infection
•
Confirmed stable HIV disease defined as documented viral load <50 copies/mL and CD4 
count >200 cells/mm3 within 6 months before enrollment, and on stable antiretroviral 
therapy for at least 6 months.
Known HCV infection
•
History of chronic HCV with evidence of sustained virological response (defined as 
undetectable HCV RNA) for ≥12 weeks following HCV treatment or without evidence of 
HCV RNA viremia (undetectable HCV viral load).
Known HBV infection
Confirmed inactive chronic HBV infection, defined as HBsAg present for ≥6 months and the 
following:
•
HBeAg negative, anti-HBe positive
•
Serum HBV DNA <2000 IU/mL
•
Persistently normal ALT and/or AST levels
•
In those who have had a liver biopsy performed, findings that confirm the absence of 
significant necroinflammation.
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10.5. Appendix 5: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
2019-nCoV
novel coronavirus 2019
AE
adverse event
AESI
adverse event of special interest
app
application
ALT
alanine aminotransferase
ARDS
adult respiratory distress syndrome
AST
aspartate aminotransferase
BiPaP
bilevel positive airway pressure
BMI
body mass index
BNP
brain natriuretic peptide
BP
blood pressure
CBER
Center for Biologics Evaluation and Research
CDC
Centers for Disease Control and Prevention (United States)
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CPaP
continuous positive airway pressure
CRF
case report form
CRO
contract research organization
CRP
C-reactive protein
CSR
clinical study report
CT
computed tomography
CVA
cerebrovascular accident
DART
developmental and reproductive toxicology
DBP
diastolic blood pressure
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EC
ethics committee
ECG
electrocardiogram
ECMO
extracorporeal membrane oxygenation
eCRF
electronic case report form
EDD
estimated delivery date
e-diary
electronic diary
EDP
exposure during pregnancy
EMA
European Medicines Agency
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Abbreviation
Term
ESR
erythrocyte sedimentation rate
EU
European Union
EUA
emergency use authorization
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FiO2
fraction of inspired oxygen
GA
gestational age
GBS
group B streptococcus
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GI
gastrointestinal
GMC
geometric mean concentration
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HBV
hepatitis B virus
HCP
healthcare provider
HCV
hepatitis C virus
HELLP
hemolysis, elevated liver enzymes, and low platelet count
HIC
Hepatic Injury Council
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HR
heart rate
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICU
intensive care unit
ID
identification
IgG
immunoglobulin G
IL-6
interleukin 6
IMP
investigational medicinal product
IND
investigational new drug
INR
international normalized ratio
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IRB
institutional review board
IRC
internal review committee
IRR
illness rate ratio
IRT
interactive response technology
IWR
interactive Web-based response
LDH
lactate dehydrogenase
LFT
liver function test
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Abbreviation
Term
LLOQ
lower limit of quantitation
LMP
last menstrual period
LNP
lipid nanoparticle
LS
least squares
MERS
Middle East respiratory syndrome
MIS-C
multisystem inflammatory syndrome in children
mITT
modified intent-to-treat
modRNA
nucleoside-modified messenger ribonucleic acid
MRI
magnetic resonance imaging
mRNA
messenger ribonucleic acid
N
SARS-CoV-2 nucleoprotein
N/A
not applicable
NAAT
nucleic acid amplification test
NaCl
sodium chloride
NI
noninferiority
NIMP
noninvestigational medicinal product
PASS
postauthorization safety study
P2 S
SARS-CoV-2 full-length, P2 mutant, “heads up,” prefusion spike 
glycoprotein
PaO2
partial pressure of oxygen, arterial
PD
pharmacodynamic(s)
PI
principal investigator
PPE
personal protective equipment
PT
prothrombin time
RCDC
reverse cumulative distribution curve
RMP
risk management plan
RNA
ribonucleic acid
RR
respiratory rate
RSV
respiratory syncytial virus
RT-PCR
reverse transcription–polymerase chain reaction
S
spike protein
S1
spike protein S1 subunit
SAE
serious adverse event
SAP
statistical analysis plan
SARS
severe acute respiratory syndrome
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SBP
systolic blood pressure
SoA
schedule of activities
SOP
standard operating procedure
SpO2
oxygen saturation as measured by pulse oximetry
SRM
study reference manual
SRSD
single reference safety document
CCI

PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591015
Final Protocol Amendment 5, 08 March 2022
PFIZER CONFIDENTIAL
Page 137
Abbreviation
Term
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
TH1
T-helper type 1
ULN
upper limit of normal
US
United States
VAED
vaccine-associated enhanced disease
VE
vaccine efficacy
WHO
World Health Organization
CCI

PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591015
Final Protocol Amendment 5, 08 March 2022
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Page 138
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Final Protocol Amendment 5, 08 March 2022
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CCI

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