A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF RESPIRATORY SYNCYTIAL VIRUS PREFUSION F SUBUNIT VACCINE WHEN COADMINISTERED WITH SEASONAL INACTIVATED INFLUENZA VACCINE IN ADULTS ≥65 YEARS OF AGE
Phase: PHASE3
Conditions: Respiratory Syncytial Virus
Sponsor: Pfizer

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671006
Final Protocol Amendment 1, 29 August 2022
PFIZER CONFIDENTIAL
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY 
TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF 
RESPIRATORY SYNCYTIAL VIRUS PREFUSION F SUBUNIT VACCINE WHEN 
COADMINISTERED WITH SEASONAL INACTIVATED INFLUENZA VACCINE 
IN ADULTS ≥65 YEARS OF AGE
Study Intervention Number:
PF-06928316 
Study Intervention Name:
Respiratory Syncytial Virus (RSV) Vaccine 
US IND Number:
017931
EudraCT Number:
N/A
ClinicalTrials.gov ID:
NCT05301322
Protocol Number:
C3671006
Phase:
3
Brief Title: Safety and Immunogenicity of RSVpreF Coadministered With SIIV in Adults 
≥65 Years of Age
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.

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671006
Final Protocol Amendment 1, 29 August 2022
PFIZER CONFIDENTIAL
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Document History
Document 
Version Date
Original protocol
30 August 2021 
Protocol amendment 1
29 August 2022
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any protocol administrative change
letter(s).
Protocol Amendment Summary of Changes Table 
Amendment 1 (29 August 2022)
Overall Rationale for the Amendment: Sample size was modified because of operational 
delays impacting the potential pool of eligible participants.
Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 1.1 Synopsis
Section 1.2 Study Design 
Schema
Section 4.1 Overall Design
Number of participants changed 
from 2230 to 1400 and group size 
from 1115 to 700
Change in sample 
size
Substantial
Table 6 Primary Endpoint 
Analysis
Modified the statement for 
declaring immunogenicity 
equivalence statement 
Change in sample 
size
Substantial
Sections 9.1.2.1, 9.1.2.2
Statistical Hypotheses
Modified statistical hypothesis for 
RSV and SIIV immunogenicity 
Change in sample 
size
Substantial
Section 9.5 Sample Size 
Determination
Provided the rationale for 
changing the sample size and
modified the power calculation
Change in sample 
size
Substantial
Table 9 Sample Size 
Determination
Adjusted the power for 
noninferiority 
Change in sample 
size
Substantial
Title Page
Added clinical trial number
Missing information
Nonsubstantial
Document History
Added Amendment 1
Tracking document 
history
Nonsubstantial
Summary of Changes Table
New
Lists the changes 
incorporated into 
Amendment 1
Nonsubstantial
Section 2.2.1 Clinical 
Overview
Updated RSV program study 
details
To include the latest 
data
Nonsubstantial

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
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Final Protocol Amendment 1, 29 August 2022
PFIZER CONFIDENTIAL
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 6.10.3 Permitted 
Nonstudy Vaccines and 
Medications
Clarified permitted use of 
corticosteroids
Incorporation of 
PACL 1
Nonsubstantial
Section 6.10.4 Recording 
Nonstudy Vaccinations and 
Concomitant Medications
Combined the 2 statements on 
COVID-19 vaccination record 
keeping into a single statement for 
clarification purposes only
Incorporation of 
PACL 1 
Nonsubstantial
Section 10.1.3 Informed 
Consent Process
Clarified text regarding the need 
to reconsent participants
Protocol template 
change
Nonsubstantial
Appendix 8 Abbreviations
Changed msLRTI to LRTI
Added GMC
Reflects change to 
term as done in Study 
C3671013, added 
missing entry
Nonsubstantial
Throughout document
Formatting modifications
Style change
Nonsubstantial
Section 9 Statistical 
Considerations, Table 5 to 
Table 9
Removed abbreviations from 
footnote
Style change
Nonsubstantial

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671006
Final Protocol Amendment 1, 29 August 2022
PFIZER CONFIDENTIAL
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
1. PROTOCOL SUMMARY...................................................................................................10
1.1. Synopsis ..................................................................................................................10
1.2. Study Design Schema..............................................................................................14
1.3. Schedule of Activities .............................................................................................15
2. INTRODUCTION ...............................................................................................................16
2.1. Study Rationale .......................................................................................................17
2.2. Background .............................................................................................................17
2.2.1. Clinical Overview.......................................................................................17
2.3. Benefit/Risk Assessment.........................................................................................19
2.3.1. Risk Assessment.........................................................................................20
2.3.2. Benefit Assessment.....................................................................................22
2.3.3. Overall Benefit/Risk Conclusion................................................................22
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ...........................................................22
4. STUDY DESIGN.................................................................................................................24
4.1. Overall Design.........................................................................................................24
4.2. Scientific Rationale for Study Design.....................................................................25
4.2.1. Choice of Contraception/Barrier Requirements .........................................25
4.3. Justification for Dose ..............................................................................................25
4.4. End of Study Definition ..........................................................................................26
5. STUDY POPULATION......................................................................................................26
5.1. Inclusion Criteria.....................................................................................................26
5.2. Exclusion Criteria....................................................................................................27
5.3. Lifestyle Considerations..........................................................................................29
5.3.1. Contraception..............................................................................................29
5.4. Screen Failures ........................................................................................................29
5.5. Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention...........................29
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................30
6.1. Study Intervention(s) Administered........................................................................30
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine........30

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6.1.2. Concomitant Seasonal Inactivated Influenza Vaccine ...............................31
6.2. Administration.........................................................................................................31
6.3. Medical Devices......................................................................................................32
6.4. Preparation, Handling, Storage, and Accountability...............................................32
6.4.1. Preparation and Dispensing........................................................................33
6.5. Measures to Minimize Bias: Randomization and Blinding.....................................33
6.5.1. Randomization to Study Intervention.........................................................33
6.5.2. Blinding Arrangements...............................................................................34
6.5.2.1. Blinding of Study Site Personnel ..............................................34
6.5.2.2. Blinding of the Sponsor.............................................................34
6.5.3. Breaking the Blind......................................................................................34
6.6. Study Intervention Compliance...............................................................................34
6.7. Dose Modification...................................................................................................34
6.8. Continued Access to Study Intervention After the End of the Study......................35
6.9. Treatment of Overdose............................................................................................35
6.10. Concomitant Therapy............................................................................................35
6.10.1. Prohibited Concomitant Vaccinations and Medications...........................35
6.10.2. Withholding Periods for Concomitant Vaccinations and 
Medications......................................................................................................35
6.10.3. Permitted Nonstudy Vaccines and Medications During the Study ..........36
6.10.4. Recording Nonstudy Vaccinations and Concomitant Medications..........36
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................37
7.1. Discontinuation of Study Intervention ....................................................................37
7.2. Participant Discontinuation/Withdrawal From the Study.......................................37
7.2.1. Withdrawal of Consent...............................................................................38
7.3. Lost to Follow-Up ...................................................................................................38
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................39
8.1. Efficacy and/or Immunogenicity Assessments .......................................................39
8.1.1. Efficacy Assessments .................................................................................39
8.1.2. Immunogenicity Assessments ....................................................................40
8.1.2.1. Blood Collection .......................................................................40

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671006
Final Protocol Amendment 1, 29 August 2022
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8.1.2.2. RSV Vaccine Antibody Testing................................................40
8.1.2.3. SIIV Immune Response Testing ...............................................40
8.1.2.4. Exploratory Assays, Including Immunogenicity 
Assessments and Assay Development...............................................40
8.1.3. Biological Samples.....................................................................................41
8.2. Safety Assessments .................................................................................................41
8.2.1. Physical Examinations................................................................................41
8.2.2. Vital Signs ..................................................................................................41
8.2.3. Electronic Diary..........................................................................................41
8.2.3.1. Local Reactions – Reactogenicity.............................................42
8.2.3.2. Systemic Events ........................................................................43
8.2.3.3. Fever Monitoring.......................................................................45
8.2.4. Clinical Safety Laboratory Assessments ....................................................45
8.2.5. Pregnancy Testing ......................................................................................45
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................45
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......46
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................47
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................47
8.3.2. Method of Detecting AEs and SAEs ..........................................................47
8.3.3. Follow-Up of AEs and SAEs......................................................................47
8.3.4. Regulatory Reporting Requirements for SAEs...........................................47
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................48
8.3.5.1. Exposure During Pregnancy......................................................48
8.3.5.2. Exposure During Breastfeeding ................................................50
8.3.5.3. Occupational Exposure .............................................................50
8.3.6. Cardiovascular and Death Events...............................................................50
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................50
8.3.8. Adverse Events of Special Interest.............................................................50
8.3.9. Medical Device Deficiencies......................................................................51
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........51

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8.3.9.2. Follow-Up of Medical Device Deficiencies..............................51
8.3.9.3. Prompt Reporting of Device Deficiencies to the Sponsor ........51
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................52
8.3.10. Medication Errors.....................................................................................52
8.4. Pharmacokinetics ....................................................................................................53
8.5. Genetics...................................................................................................................53
8.6. Biomarkers ..............................................................................................................53
8.7. Immunogenicity Assessments.................................................................................53
8.8. Health Economics ...................................................................................................53
8.9. Study Procedures.....................................................................................................54
8.9.1. Visit 1 – Vaccination 1 (Clinic, Day 1)......................................................54
8.9.2. Visit 2 – Vaccination 2 (Clinic, 28 to 35 Days After Visit 1) ....................56
8.9.3. Visit 3 Follow-Up After Vaccination 2 (Clinic, 28 to 35 Days After 
Visit 2) .............................................................................................................57
8.9.4. Unscheduled Reactogenicity Visits for a Grade 3 or Suspected 
Grade 4 Reaction..............................................................................................58
9. STATISTICAL CONSIDERATIONS ................................................................................59
9.1. Statistical Hypotheses .............................................................................................59
9.1.1. Estimands....................................................................................................59
9.1.2. Statistical Hypotheses.................................................................................60
9.1.2.1. Statistical Hypothesis for Primary RSV Immunogenicity ........60
9.1.2.2. Statistical Hypothesis for SIIV Immunogenicity ......................60
9.1.3. Multiplicity Adjustment..............................................................................60
9.2. Analysis Sets ...........................................................................................................61
9.3. Statistical Analyses .................................................................................................61
9.3.1. General Considerations...............................................................................61
9.3.1.1. Analyses for Binary Data ..........................................................62
9.3.1.2. Analyses for Continuous Data...................................................62
9.3.2. Primary Endpoint(s)....................................................................................63
9.3.3. Secondary Endpoint(s)................................................................................64
9.3.4. Exploratory Endpoint(s) .............................................................................64

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Final Protocol Amendment 1, 29 August 2022
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9.4. Interim Analyses .....................................................................................................64
9.5. Sample Size Determination.....................................................................................64
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................66
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............66
10.1.1. Regulatory and Ethical Considerations ....................................................66
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................66
10.1.2. Financial Disclosure .................................................................................67
10.1.3. Informed Consent Process ........................................................................67
10.1.4. Data Protection .........................................................................................68
10.1.5. Committees Structure ...............................................................................68
10.1.5.1. Data Monitoring Committee ...................................................68
10.1.6. Dissemination of Clinical Study Data ......................................................68
10.1.7. Data Quality Assurance ............................................................................70
10.1.8. Source Documents....................................................................................71
10.1.9. Study and Site Start and Closure ..............................................................71
10.1.10. Publication Policy...................................................................................72
10.1.11. Sponsor’s Qualified Medical Personnel .................................................73
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................74
10.2.1. Definition of AE .......................................................................................74
10.2.2. Definition of an SAE ................................................................................75
10.2.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................77
10.2.4. Reporting of SAEs....................................................................................80
10.3. Appendix 3: Contraceptive and Barrier Guidance ................................................81
10.3.1. Male Participant Reproductive Inclusion Criteria....................................81
10.3.2. Female Participant Reproductive Inclusion Criteria.................................81
10.3.3. Woman of Childbearing Potential ............................................................81
10.3.4. Contraception Methods.............................................................................82
10.4. Appendix 4: Liver Safety: Suggested Actions and Follow-Up Assessments .......83

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Protocol C3671006
Final Protocol Amendment 1, 29 August 2022
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10.5. Appendix 5: AEs, ADEs, SAEs, SADEs, USADEs, and Device 
Deficiencies Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting in Medical Device Studies .............................................85
10.5.1. Definition of AE and ADE .......................................................................85
10.5.2. Definition of SAE, SADE, and USADE ..................................................85
10.5.3. Definition of Device Deficiency...............................................................86
10.5.4. Recording/Reporting and Follow-Up of Medical Device 
Deficiencies......................................................................................................86
10.5.5. Reporting of SAEs....................................................................................88
10.5.6. Reporting of SADEs.................................................................................88
10.6. Appendix 6: Alternative Measures During Public Emergencies ..........................89
10.6.1. Telehealth Visits.......................................................................................89
10.7. Appendix 7: Criteria for Allowing Inclusion of Participants With Chronic 
Stable HIV, HCV, or HBV Infection ........................................................................90
10.8. Appendix 8: Abbreviations ...................................................................................91
11. REFERENCES ..................................................................................................................94
LIST OF TABLES
Table 1.
Vaccine Administration Group.................................................................31
Table 2.
Grading Scale for Local Reactions...........................................................43
Table 3.
Grading Scale for Systemic Events ..........................................................44
Table 4.
Ranges for Fever.......................................................................................45
Table 5.
Analysis Sets.............................................................................................61
Table 6.
Primary Endpoint Analyses ......................................................................63
Table 7.
Secondary Endpoint Analyses ..................................................................64
Table 8.
Exploratory Endpoint Analyses................................................................64
Table 9.
Sample Size Determination ......................................................................65

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
Protocol C3671006
Final Protocol Amendment 1, 29 August 2022
PFIZER CONFIDENTIAL
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1. PROTOCOL SUMMARY
1.1. Synopsis
Brief Title: Safety and Immunogenicity of RSVpreF Coadministered With SIIV in 
Adults ≥65 Years of Age
Rationale
Annual seasonal influenza vaccination is recommended in a number of countries around the 
world to prevent influenza in children and adults. Older adults, particularly those with 
medical comorbidities, are at increased risk of influenza morbidity and mortality and are 
recommended to receive high-dose or adjuvanted influenza vaccine formulations. RSV and 
influenza are both typically seasonal diseases, with peaks during winter in temperate 
climates. Therefore, it is a possibility that RSVpreF may be given at the same time as 
seasonal influenza vaccine.
The purpose of this study is to assess the safety and immunogenicity of RSVpreF when 
coadministered with SIIV compared to sequential administration of the vaccines when given 
1 month apart (SIIV followed by RSVpreF). Additionally, the study will contribute data 
supporting the development of RSVpreF as a prophylactic vaccine against RSV disease in 
infants through maternal immunization and in older adults through active vaccination.
Objectives, Endpoints, and Estimands
Objectives
Endpoints
Estimands
Primary Safety 
To evaluate the safety profiles 
of RSVpreF when 
coadministered with SIIV 
(RSVpreF + SIIV) or when
administered 1 month after 
SIIV.

Local reactions (redness, 
swelling, and pain at the 
injection site) self-reported on 
e-diaries for 7 days after 
vaccination.

Systemic events (fever, fatigue, 
headache, nausea, vomiting, 
diarrhea, muscle pain, and joint 
pain) self-reported on e-diaries 
for 7 days after vaccination.

AEs.

SAEs.
In participants receiving 1 dose 
of study intervention and having 
safety follow-up after 
vaccination from each vaccine 
group: 
The percentage of participants 
reporting prompted local 
reactions and systemic events 
within 7 days after vaccination 
with RSVpreF or placebo.
The percentage of participants 
reporting AEs and SAEs within 
1 month after each vaccination.

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
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Final Protocol Amendment 1, 29 August 2022
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Objectives
Endpoints
Estimands
Primary RSV Immunogenicity 
To demonstrate that the 
immune responses elicited by 
RSVpreF when 
coadministered with SIIV 
(RSVpreF + SIIV) are 
noninferior to those elicited 
by RSVpreF alone when 
administered 1 month after 
SIIV.

RSV A and RSV B NTs.
In participants in compliance 
with the key protocol criteria 
(evaluable participants): 
GMR of NTs at 1 month after 
vaccination with RSVpreF for 
each RSV subfamily (A or B) 
in RSVpreF + SIIV to RSVpreF 
alone (sequential-administration 
group).
Primary SIIV Immunogenicity 
To demonstrate that the 
immune responses elicited 
by SIIV when coadministered 
with RSVpreF 
(RSVpreF + SIIV) are 
noninferior to those elicited 
by SIIV alone.

Strain-specific HAI titers.

H3N2-neutralizing antibody 
titers (if interpretable 
H3N2-HAI titers cannot be 
obtained).
In participants in compliance 
with the key protocol criteria 
(evaluable participants): 

GMR of the strain-specific 
HAI (or H3N2-neutralizing 
antibody) titers 1 month after 
vaccination with SIIV in the 
coadministration group to the 
corresponding HAI 
(or H3N2-neutralizing 
antibody) titers in the 
sequential-administration 
group.
Secondary RSV Immunogenicity
To describe immune 
responses elicited by 
RSVpreF when 
coadministered with SIIV or 
when administered alone.

RSV A and RSV B NTs.
In participants in compliance 
with the key protocol criteria 
(evaluable participants) from 
each vaccine group:

Geometric mean of the NTs 
for RSV A and RSV B before 
vaccination and at each 
applicable visit after 
vaccination with RSVpreF.

GMFR of the NTs for RSV A 
and RSV B before vaccination 
and at each applicable visit 
after vaccination with 
RSVpreF.
Secondary SIIV Immunogenicity
To describe immune 
responses elicited by SIIV 
when coadministered with 
RSVpreF or when 
administered alone.

Strain-specific HAI titers.

H3N2-neutralizing antibody 
titers (if interpretable 
H3N2-HAI titers cannot be 
obtained).
In participants in compliance 
with the key protocol criteria 
(evaluable participants) from 
each vaccine group:

GMTs before vaccination and 
1 month after vaccination with 
SIIV.

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
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Final Protocol Amendment 1, 29 August 2022
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Objectives
Endpoints
Estimands

GMFR of strain-specific HAI 
titers (or H3N2-neutralizing 
antibody titers if interpretable 
H3N2-HAI titers cannot be 
obtained) before vaccination 
and 1 month after vaccination 
with SIIV.
 
 
 
 
 
 
 
Exploratory SIIV Immunogenicity
To further describe immune 
responses elicited by SIIV 
when coadministered with 
RSVpreF or when 
administered alone.

Strain-specific HAI titers.

H3N2-neutralizing antibody 
titers (if interpretable 
H3N2-HAI titers cannot be 
obtained).
Overall Design
Brief Summary
This Phase 3, multicenter, parallel-group, placebo-controlled, randomized, double-blind 
study will be conducted in Australia and/or another southern hemisphere country.
Healthy adults ≥65 years of age will be randomized 1:1 to either the coadministration 
group (RSVpreF + SIIV)/placebo or the sequential-administration group 
(placebo + SIIV)/RSVpreF.
There are 3 scheduled study visits each 1 month apart. To assess immunogenicity, blood will 
be collected prior to vaccination at Visit 1 and Visit 2, and at Visit 3.
Local reactions at the RSVpreF or placebo injection site (left deltoid) and systemic events 
occurring within 7 days after each vaccination will be recorded in an e-diary device or
smartphone app.
AEs and SAEs will be collected from the signing of informed consent through study 
completion (Visit 3).
Number of Participants
Approximately 1400 healthy, older adults will be enrolled in the study.
CCI

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
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Intervention Groups and Duration
There will be 2 study groups:
Group 1 (coadministration):

Visit 1: (RSVpreF + SIIV)

Visit 2: placebo 
Group 2 (sequential administration):

Visit 1: (placebo + SIIV) 

Visit 2: RSVpreF
Each participant will participate in the study for approximately 2 months. Based on an 
estimated 2-month enrollment period, the study duration will be approximately 4 months.
Statistical Methods
GMRs of RSV NTs in the coadministration group to the sequential-administration group for 
RSV A and RSV B at 1 month after vaccination with RSVpreF will be provided along with 
associated 2-sided 95% CIs. GMRs of strain-specific HAI titers in the coadministration 
group to the sequential-administration group at 1 month after vaccination with SIIV will be 
provided along with associated 2-sided 95% CIs. Using a 1.5-fold margin, noninferiority will 
be declared if the lower bound of the 2-sided 95% CI for each GMR is greater than 0.667 for 
all SIIV strains and for both RSV A and RSV B.
The primary safety objective will be evaluated by descriptive summary statistics for local 
reactions, systemic events, AEs, and SAEs after each vaccination for each vaccine group. 
A 3-tier approach will be used to summarize AEs.

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1.2. Study Design Schema
Healthy Adults
≥65 Years of Age
Visit 1
Visit 2
28-35 Days after Visit 1
Visit 3
28-35 Days after Visit 2
Day 1 
Vaccination 1
Month 1
Vaccination 2
Month 2
Follow-Up
   Study Group 
     (n)
       Injection site:
     deltoid
   Left            Right
           Injection site:
         deltoid
      Left
Group 1
700
Coadministration
RSVpreF + 
SIIV/placebo
RSVpreF
SIIV
    Placebo
Group 2
700
Sequential 
administration 
Placebo + 
SIIV/RSVpreF
Placebo
SIIV
     RSVpreF
Safety assessments: reactogenicity, AEs/SAEs
30-mL blood draw
120 µg RSVpreF (blinded administration)
SIIV (unblinded administration)
Placebo (blinded administration)

PF-06928316 (Respiratory Syncytial Virus [RSV] Vaccine) 
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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures. Refer to Study 
Assessments and Procedures in Section 8 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, to conduct evaluations or 
assessments required in order to protect the well-being of the participant.
Schedule of Activities
Visit Identifier
Visit 1
Visit 2
Visit 3
Visit Description
Day 1
Vaccination 1
Month 1
Vaccination 2
Month 2
Visit Window 
-
28-35 Days 
after Visit 1
28-35 Days 
after Visit 2
Obtain informed consent
X
Obtain participant number via IRT
X
Obtain demography and significant medical history data
X
Record current/former tobacco usage
X
Perform clinical assessment (and physical examination if deemed 
necessary) 
X
Record nonstudy vaccinations, review concomitant medication use 
X
X
X
Review inclusion and exclusion criteria and confirm eligibility
X
Obtain participant’s temperature 
X
X
Review temporary delay criteria
X
X
Obtain blood sample for antibody assessment (~30 mL)
Xa
Xa
X
Obtain randomization number and kit assignment from IRT 
X
Explain/review participant communication methods, assist with 
downloading the e-diary application, or issue provisioned e-diary 
device, if required.
X
Provide e-diary training, issue thermometer and measuring device
X
Xb
Administer SIIV in right deltoid muscle
X
Administer study intervention in left deltoid muscle 
X
X
Discuss contraceptive use (as appropriate)
X
X
Issue ECC and explain its purpose and use
X
Xb
Postvaccination observation (30 minutes) and immediate reaction 
assessment
X
X
Review e-diary data,(daily during the 7 days after vaccination)
X
X
Review e-diary for ongoing events and stop dates, collect e-diaryc
X
X
Record AEs/SAEs and stop dates for previously reported events.
X
X
X
a.
Blood sample must be collected before vaccination.
b.
Issue replacement thermometer, measuring device, and ECC, only if required
c.
Collect provisioned e-diaries at Visit 3 only.

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2. INTRODUCTION
RSV is a major cause of respiratory infection in all ages, which can result in severe illness in 
both infants and older adults. There are 2 antigenic variants of RSV: subgroups A (RSV A) 
and B (RSV B) that cocirculate.1 Like influenza, RSV infection follows a seasonal pattern, 
causing yearly wintertime epidemics in temperate climates, usually between late autumn and 
early spring. In tropical climates, the outbreaks are generally associated with rainy seasons 
but are more unpredictable and frequently continuous.2 Due to the COVID-19 pandemic, 
which spread worldwide in 2020 and 2021, the seasonality of several pathogens, including 
RSV, has been disrupted and the shift of peak incidence has been observed in a majority of 
geographies. Therefore the RSV season is less predictable with respect to onset and 
duration.3
Adults ≥60 years of age have an increased risk of RSV infection, which can trigger 
exacerbations of underlying comorbid conditions, such as COPD and CHF. RSV infection 
has been associated with up to 22% of acute COPD exacerbations in prospective cohort 
studies and 11% of wintertime hospitalizations for COPD exacerbations.4 Current 
epidemiology shows that RSV is responsible for approximately 177,000 hospitalizations and 
14,000 deaths annually in US adults 65 years of age and older.5 Morbidity is significant 
among adults hospitalized with RSV disease, with 18% requiring intensive care, 31% 
needing home health services at discharge, and 26% dying within 1 year of hospitalization.6
In the US, RSV disease incidence rates in older adults are approximately half those of 
influenza, with variation year to year.7 Incidence rates and risk for severe complications from 
RSV infection are higher among immunocompromised adults and those with chronic 
conditions (eg, cardiopulmonary or renal disease, hematological malignancies, receipt of 
chemotherapy, or HIV infection).8,9 However, the burden of adult RSV disease could be 
underestimated since testing for RSV is less common in older adults than in children. RSV 
disease in adults is also difficult to diagnose based on clinical signs and symptoms alone, 
and, prior to the broader use of more sensitive detection methods, laboratory confirmation of 
RSV in adults was challenging because of low levels of virus shedding.4
RSV disease management in adults is limited to supportive measures, such as hydration and 
oxygenation. Aerosolized ribavirin has limited evidence of effectiveness and is 
predominantly restricted to severely immunocompromised hospitalized patients because of 
inconvenient administration, teratogenicity, anemia concerns, and high cost. Prevention of 
RSV disease via active immunization has the potential to make a significant impact in this 
population, therefore making vaccine development a high priority.9,10

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2.1. Study Rationale
Annual seasonal influenza vaccination is recommended in a number of countries around the 
world to prevent influenza in children and adults. Older adults, particularly those with 
medical comorbidities, are at increased risk of influenza morbidity and mortality and are 
recommended to receive high-dose or adjuvanted influenza vaccine formulations.11,12 RSV 
and influenza are both typically seasonal diseases, with peaks during winter in temperate 
climates.2 Therefore, it is a possibility that RSVpreF may be given at the same time as 
seasonal influenza vaccine.

The purpose of this study is to assess the safety and immunogenicity of RSVpreF when 
coadministered with SIIV, compared to sequential administration of the vaccines when 
given 1 month apart (SIIV followed by RSVpreF). Additionally, the study will contribute 
data supporting the development of RSVpreF as a prophylactic vaccine against RSV 
disease in infants through maternal immunization and in older adults through preventive
vaccination.
2.2. Background
The vaccine under evaluation in this study is a bivalent RSV prefusion F subunit vaccine 
developed by Pfizer. The RSV F glycoprotein facilitates fusion of the virion and host cell 
membrane through a dramatic transition from an unstable but highly immunogenic prefusion 
conformation to the more stable postfusion state. Preclinical studies show that prefusion F 
elicits much higher neutralizing antibody titers than postfusion F and that the most potent 
neutralizing antibodies from postinfection human sera target the prefusion form. RSVpreF is 
composed of engineered, stabilized, trimeric, prefusion F glycoproteins matching the A and 
B subgroups to help ensure the broadest coverage against RSV illness.
Pfizer’s RSV stabilized prefusion F subunit vaccine (RSVpreF) is a prophylactic vaccine 
that is being developed for 2 indications:

Older Adult: Prevention of RSV-associated LRTI in adults 60 years of age and older via 
active immunization.

Maternal: Prevention of LRTI-RSV in infants by active immunization of pregnant 
women.
2.2.1. Clinical Overview
Adult Program Studies
The older adult program includes 2 Phase 1/2 studies, the human challenge study, and 
2 Phase 3 studies.

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
In the Phase 1/2 C3671001 study, 1233 healthy adults 18 through 49 and 50 through
85 years of age received the 3 dose levels of RSVpreF (60 µg, 120 µg, and 240 µg), with 
or without Al(OH)3, or placebo, administered with or without concomitant flu vaccine. 
The results have shown the vaccine was well tolerated and immunogenic in both age 
groups. RSVpreF elicited robust neutralizing responses against RSV A and RSV B 
1 month after vaccination for both age groups across all vaccine dose levels and 
formulations and remained high through the 12 months after vaccination. In 
616 vaccinated participants in the 50 to 85 years age group, RSV 50% NT GMFRs were 
high across all arms ranging from 9 to 13 from before vaccination to 1 month after 
vaccination and from 3 to 4 from before vaccination to 12 months after vaccination for 
RSV A and RSV B. When RSVpreF was coadministered with SIIV, trends in immune 
responses to RSVpreF were inconsistent depending on dose level and formulation. 
Immune responses to SIIV trended lower when coadministered with RSVpreF for both 
age groups, but the impact was less in the 65 to 85 years age group, compared to the 
18 through 49 year age group. RSVpreF was safe and well tolerated when administered 
alone or with SIIV, with no major differences observed across all dose levels and 
formulations. Most reported local reactions or systemic events were mild or moderate in 
severity. Proportions of participants reporting AEs were generally similar across 
RSVpreF groups, and no SAEs were considered related to the study intervention.

The Phase 1/2 C3671002 study in 313 older adults 65 to 85 years of age examined 3 dose 
levels of RSVpreF with Al(OH)3 (60 µg, 120 µg, and 240 µg), formulated with or 
without CpG adjuvant, given as a single dose with concomitant SIIV or in a 2-dose 
regimen administered 2 months apart. All RSVpreF doses and formulations elicited high 
RSV A and RSV B neutralizing antibody GMTs 1 month after vaccination (GMFRs 
ranging from 4.8 to 11.6 and 4.5 to 14.1, respectively). CpG-containing formulations did 
not further increase neutralizing GMTs compared to RSVpreF with or without Al(OH)3. 
GMTs in all groups declined but remained higher than baseline (before vaccination) and 
placebo (SIIV only) at 12 months after vaccination (GMFRs ranging from 2.1 to 3.5 and 
2.2 to 4.3, respectively). No increase in GMTs was observed 1 month after Vaccination 2 
(GMFR of 0.9). All doses and formulations were safe and well tolerated. Immune 
responses to SIIV demonstrated by HAI titers and H3N2-neutralizing titers were similar 
or trended slightly lower in RSVpreF groups (coadministered with SIIV) compared to the 
placebo group (received SIIV only), and rates of seroprotection and seroconversion 
1 month after SIIV administration were generally similar.

A Phase 2a, randomized, double-blind, placebo-controlled study to evaluate the safety, 
immunogenicity, and efficacy of RSVpreF in a virus challenge model in healthy adults 
(NCT04785612) has been conducted in 70 healthy participants 18 to 50 years of age. 
Participants received a single dose of either 120 μg RSVpreF or placebo, and 4 weeks 
later underwent intranasal challenge with RSV A Memphis 37b virus. The 
immunogenicity and efficacy of RSVpreF vaccination on virus replication, clinical 
symptoms, and incidence of symptomatic RSV infection were evaluated. The primary 
analysis of the human challenge study showed that the 120-μg dose of RSVpreF is well 
tolerated and has an acceptable safety profile. The study has demonstrated 100% efficacy 

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of RSVpreF against RT-PCR–confirmed symptomatic respiratory infection in a 
mild-to-moderate disease model.

Study C3671014 is a completed Phase 3, multicenter, parallel-group, placebo-controlled, 
randomized, double-blind lot consistency study in a population of up to 1000 healthy 
adults 18 to ≤49 years of age. The study examined the immune response and the safety 
and tolerability profiles across 3 manufactured lots of RSVpreF when administered as a 
single 120-µg dose to healthy adults. The primary analyses showed that the ratio of 
neutralizing GMTs for each of the 3 manufactured RSVpreF lots, 1 month after 
vaccination are equivalent, and that the 120-µg dose of RSVpreF is well tolerated and has 
an acceptable safety profile.

Study C3671013 is an ongoing Phase 3, multicenter, randomized, double-blind, 
placebo-controlled study to assess the safety, immunogenicity, and efficacy of RSVpreF 
in the prevention of RSV-associated LRTI in adults 60 years of age and older. Both 
healthy adults and adults with stable chronic cardiopulmonary conditions will be 
included. Approximately 10% of participants with stable chronic cardiopulmonary 
conditions, such as COPD, asthma, or CHF, will be enrolled. Up to 45,000 participants 
will be randomized to receive RSVpreF or placebo in a 1:1 ratio. This is an event-driven 
study with a target of 59 first episodes of evaluable RSV-associated LRTI cases.
Maternal Program Studies
The maternal program includes ongoing Phase 2b and 3 studies in pregnant women and a 
completed Phase 2b study in nonpregnant women. The Phase 3 lot consistency study 
C3671014 described under the adult program studies will contribute data to support the 
maternal immunization program. Analyses and ongoing safety reviews in each of these 
studies have demonstrated that RSVpreF has a good safety and tolerability profile and no 
safety signals were identified. Further details are described in the IB.
2.3. Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RSVpreF may be found in the IB, which is the SRSD for this study.
The SRSD for the SIIV will be the product information for the country where the vaccine 
was procured.

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2.3.1. Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): RSVpreF
Local reactions and 
systemic events to the 
vaccine may occur 
(injection site redness, 
injection site swelling, and 
injection site pain; fever, 
fatigue, headache, nausea, 
vomiting, diarrhea, muscle 
pain, and joint pain) 
following vaccination.
These are common adverse reactions seen 
with other vaccines13 as well as RSVpreF.
The most common events reported in Study
C3671001 were mild-to-moderate pain at 
the injection site, fatigue, headache, and 
muscle pain.

The study employs the use of a 
reactogenicity e-diary, which 
allows the investigator to 
monitor local reactions and 
systemic events in real time 
through an electronic portal. 
Severe reactions will require an 
unscheduled telephone call, and 
if required a clinic visit, to be 
conducted per the protocol.

All study participants will be 
observed for at least 30 minutes 
after vaccination.
Safety profile of a novel 
vaccine close to being, but 
not yet fully,
characterized.
Data available from completed and ongoing 
studies showed a low incidence of severe or 
serious events and no clinically concerning 
safety observations. The vaccine appears to 
be safe and well tolerated across the safety 
population and within demographic 
subgroups based on age, sex, and 
race/ethnicity.

Assessments of AEs and SAEs 
will be collected and reviewed 
throughout the study.

All participants will be 
observed for at least 30 minutes 
after vaccination.
Theoretical risk for RSV 
enhancement.
RSVpreF is being evaluated in ongoing 
clinical studies. Pfizer’s immunization 
approach circumvents the risk of 
vaccine-mediated disease enhancement that 
was observed in the 1960s following direct 
immunization of RSV-naive infants with an 
FI-RSV. FI-RSV elicited a predominantly 
nonneutralizing antibody response and a 
Th2-biased cell-mediated response, both of 
which are considered potential contributing 
factors to disease enhancement. During 
preclinical studies, in a standard cotton rat 
infectious RSV challenge model, FI-RSV 
showed pathological signs of causing 
disease enhancement, and the current Pfizer 
vaccine candidate, RSVpreF, did not. Most 
important, RSV vaccine–mediated disease 
enhancement has not been reported in 
RSV-experienced individuals after 
vaccination with any RSV vaccine 
candidate. Because older adults are 
universally RSV-experienced, they are not 
considered at risk for a disease-enhancing 
immune response to the vaccine or a 
potential exacerbation of an infection.

Assessments of AEs and SAEs 
will be collected and reviewed 
throughout the study.

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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Concomitant Vaccine: SIIV
The relevant key risks 
associated with SIIV 
include injection site pain, 
fatigue, headache, redness 
at the injection site, joint 
pain, muscle pain, and 
diarrhea.14
The risks are based on the SIIV product 
information for the country where the 
vaccine was procured.

Eligibility criteria have been 
selected to ensure that only 
appropriate participants are 
included in the study, including 
those who may have 
contraindications to SIIV 
components/administration
(see Section 5).
Coadministration of 
RSVpreF with SIIV may 
enhance local and 
systemic reactions.
RSVpreF has already been coadministered 
with SIIV in Studies C3671001 and 
C3671002 including older adult 
populations. There was no evidence of 
enhancement of local reactions and 
systemic events associated with 
concomitant administration in these studies 
and no safety concerns.

E-diary and AE data will be 
monitored by the investigator 
(or designee) and sponsor. 
Participants who develop 
exclusionary conditions during 
study conduct or participants 
with significant reactions after 
Visit 1 vaccinations or AEs 
considered by the investigator 
to present increased risk to the 
participant if he/she received 
additional study vaccinations 
may be excluded from further 
vaccinations.
Coadministration of 
RSVpreF with SIIV may 
impact the immune 
response to SIIV.
In Study C3671001, immune responses to 
SIIV trended lower when coadministered 
with RSVpreF, while in Study C3671002,
immune responses to SIIV were similar or 
slightly lower, and HAI seroprotection and 
seroconversion rates remained similar.

Based on Phase 1/2 data, this 
risk is considered low, given 
comparable seroprotection rates 
observed in the older adult 
population; however, influenza 
cases will be collected as AEs 
or SAEs.
Study Procedures
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.
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 appropriate COVID-19 
prevention strategies.

Cases of COVID-19 will be 
reported as AEs or SAEs.

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2.3.2. Benefit Assessment
Benefit considerations may include:

Potential benefit of receiving study intervention that may have clinical utility in the 
future.

Contributing to the process of developing new therapies in an area of unmet need.

Medical evaluations/assessments associated with study procedures.

Receipt of a licensed influenza vaccine.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with RSVpreF are justified by the anticipated benefits that may be 
afforded to study participants who may be at risk of RSV.
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS
Objectives
Endpoints 
Estimands
Primary Safety 
To evaluate the safety profiles 
of RSVpreF when 
coadministered with SIIV 
(RSVpreF + SIIV) or 
administered 1 month after 
SIIV.

Local reactions (redness, 
swelling, and pain at the 
injection site) self-reported on 
e-diaries for 7 days after 
vaccination.

Systemic events (fever, fatigue, 
headache, nausea, vomiting, 
diarrhea, muscle pain, and joint 
pain) self-reported on e-diaries 
for 7 days after vaccination.

AEs.

SAEs.
In participants receiving 1 dose 
of study intervention and having 
safety follow-up after 
vaccination from each vaccine 
group: 

The percentage of participants 
reporting prompted local 
reactions and systemic events 
within 7 days after 
vaccination with RSVpreF or 
placebo.

The percentage of participants 
reporting AEs and SAEs 
within 1 month after each 
vaccination.
Primary RSV Immunogenicity 
To demonstrate that the 
immune responses elicited by 
RSVpreF when 
coadministered with SIIV 
(RSVpreF + SIIV) are 
noninferior to those elicited 
by RSVpreF alone when 
administered 1 month after 
SIIV.

RSV A and RSV B NTs.
In participants in compliance 
with the key protocol criteria 
(evaluable participants): 

GMR of NTs at 1 month after 
vaccination with RSVpreF for 
each RSV subfamily (A or B) 
in RSVpreF + SIIV to 
RSVpreF alone 
(sequential-administration 
group).

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Objectives
Endpoints 
Estimands
Primary SIIV Immunogenicity 
To demonstrate that the 
immune responses elicited 
by SIIV when coadministered 
with RSVpreF 
(RSVpreF + SIIV) are 
noninferior to those elicited 
by SIIV alone.

Strain-specific HAI titers.

H3N2-neutralizing antibody 
titers (if interpretable 
H3N2-HAI titers cannot be 
obtained).
In participants in compliance 
with the key protocol criteria 
(evaluable participants): 

GMR of the strain-specific 
HAI (or H3N2-neutralizing 
antibody) titers 1 month after 
vaccination with SIIV in the 
coadministration group to 
the corresponding HAI 
(or H3N2-neutralizing 
antibody) titers in the 
sequential-administration 
group
Secondary RSV Immunogenicity
To describe immune 
responses elicited by 
RSVpreF when 
coadministered with SIIV or 
when administered alone.

RSV A and RSV B NTs.
In participants in compliance 
with the key protocol criteria 
(evaluable participants) from 
each vaccine group:

Geometric mean of the NTs 
for RSV A and RSV B before 
vaccination and at each 
applicable visit after 
vaccination with RSVpreF.

GMFR of the NTs for RSV A 
and RSV B before vaccination 
and at each applicable visit 
after vaccination with 
RSVpreF.
Secondary SIIV Immunogenicity
To describe immune 
responses elicited by SIIV 
when coadministered with 
RSVpreF or when 
administered alone.

Strain-specific HAI titers.

H3N2-neutralizing antibody 
titers (if interpretable 
H3N2-HAI titers cannot be 
obtained).
In participants in compliance 
with the key protocol criteria 
(evaluable participants) from 
each vaccine group:

GMTs before vaccination and 
1 month after vaccination with 
SIIV.

GMFR of strain-specific HAI 
titers (or H3N2-neutralizing 
antibody titers if interpretable 
H3N2-HAI titers cannot be 
obtained) before vaccination 
and 1 month after vaccination 
with SIIV.

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Objectives
Endpoints 
Estimands
 
 
 
 
 
 
 
Exploratory SIIV Immunogenicity
To further describe immune 
responses elicited by SIIV 
when coadministered with 
RSVpreF or when 
administered alone.

Strain-specific HAI titers.

H3N2-neutralizing antibody 
titers (if interpretable 
H3N2-HAI titers cannot be 
obtained).
4. STUDY DESIGN
4.1. Overall Design
This Phase 3, multicenter, parallel-group, placebo-controlled, randomized, double-blind 
study will be conducted in Australia and/or another southern hemisphere country.
Healthy adults >65 years of age will be randomized 1:1 to either the coadministration 
group (RSVpreF + SIIV)/placebo or the sequential-administration group 
(placebo + SIIV)/RSVpreF. This study design intends to use a single lot of SIIV that is 
specifically indicated for use in adults ≥65 years of age; however, the SIIV ultimately used 
may be determined by supply availability.
There are 3 scheduled study visits each 1 month apart. To assess immunogenicity, 30 mL 
blood will be collected prior to vaccination at Visit 1 and Visit 2, and at Visit 3.
Local reactions (redness, swelling, and pain at the injection site) occurring at the RSVpreF or 
placebo injection site (left deltoid) and systemic events (fever, headache, fatigue, nausea, 
vomiting, diarrhea, muscle pain, and joint pain) occurring within 7 days after each 
vaccination visit (Visit 1 and Visit 2) will be prompted for and collected daily by the 
participant in an e-diary device or smartphone app. SIIV injection site reactions will not be 
routinely collected in the e-diary.
AEs and SAEs will be collected from the signing of informed consent through Visit 3.
Number of Participants
Approximately 1400 participants (700 per group) will be enrolled in the study. Participants 
who withdraw or are withdrawn from the study after randomization will not be replaced, 
regardless of the reason for withdrawal.
CCI

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Intervention Groups and Duration
There will be 2 study groups: 
Group 1 (coadministration):

Visit 1: (RSVpreF + SIIV) 

Visit 2: placebo 
Group 2 (sequential administration): 

Visit 1: (placebo + SIIV) 

Visit 2: RSVpreF
Each participant will participate in the study for approximately 2 months. Based on an 
estimated 2-month enrollment period, the total study duration will be approximately 
4 months.
4.2. Scientific Rationale for Study Design
See Section 2.1.
4.2.1. Choice of Contraception/Barrier Requirements 
There is no suspicion of human teratogenicity based on the available reproductive toxicity 
data; however, human reproductive safety data are limited, and a Phase 3 study of RSVpreF 
in pregnant women is ongoing. Therefore, the use of a highly effective method of 
contraception is required (see Section 10.3, Appendix 3).
4.3. Justification for Dose
The final dose and formulation of RSVpreF selected for use in this study is based on the 
safety and immunogenicity data from 3 Phase 1/2 studies and the efficacy evaluation in the 
human challenge study.

The FIH study in adults 18 through 85 years of age evaluated the safety, tolerability, and 
immunogenicity of 3 escalating RSVpreF dose levels of 60 μg, 120 μg, and 240 μg, 
with or without Al(OH)3, when administered alone or concomitantly with SIIV
(Study C3671001).

A study in older adults 65 through 85 years of age evaluated the safety, tolerability, and 
immunogenicity of 60 μg, 120 μg, and 240 μg RSVpreF doses formulated with 
Al(OH)3 or a CpG/Al(OH)3 adjuvant, or 240 µg RSVpreF with RSV antigens alone, 
when administered concomitantly with SIIV (Study C3671002).

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
A study in healthy adults 18 through 50 years of age evaluated the safety,
immunogenicity, and efficacy of 120 µg RSVpreF in a virus challenge model 
(NCT04785612).
Based on the Phase 1/2 studies (C3671001 and C3671002), no substantial differences were 
observed between the immunogenicity or reactogenicity of the 120-µg and 240-µg dose 
levels or of formulations with and without Al(OH)3 or CpG/Al(OH)3. Therefore, the 120-µg 
without-Al(OH)3 formulation was chosen for the human challenge study. The acceptable 
reactogenicity and safety profile along with the high efficacy demonstrated in the
primarily-upper-respiratory-tract and mild-to-moderate disease human challenge model led to 
the selection of a 120-µg dose for the RSV Phase 3 studies.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study.
A participant is considered to have completed the study when she/he has completed all study 
visits.
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 the following criteria apply:
Age and Sex:
1. Male and female participants ≥65 years of age at the time of consent.
Refer to Appendix 3 for reproductive criteria for male (Section 10.3.1) and female 
(Section 10.3.2) participants.

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Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with scheduled visits, laboratory tests, 
lifestyle considerations, and other study procedures, including daily completion of the 
e-diary for 7 days after each study vaccination.
3. Healthy participants who are determined by medical history, physical examination 
(if required), and clinical judgment of the investigator to be eligible for inclusion in the 
study.
Note: Healthy 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 participants with 
known stable infection with HIV, HCV, or HBV can be found in Section 10.7, 
Appendix 7.
Informed Consent:
4. 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.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Bleeding diathesis or condition associated with prolonged bleeding time that may 
contraindicate IM injection.
2. 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.
3. Allergy to egg proteins (egg or egg products) or chicken proteins.
4. History of Guillain-Barré syndrome.
5. Serious chronic disorder, including metastatic malignancy, end-stage renal disease with 
or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the 
investigator’s opinion, excludes the participant from participating in the study.
6. Immunocompromised individuals with known or suspected immunodeficiency, as 
determined by history and/or laboratory/physical examination.
7. 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.

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Prior/Concomitant Therapy:
8. Previous vaccination with any licensed or investigational RSV vaccine at any time prior 
to enrollment, or planned receipt throughout the study of nonstudy RSV vaccine.
9. Previous vaccination with any influenza vaccine within 6 months before study 
intervention administration, or planned receipt of any nonstudy licensed or 
investigational influenza vaccine during study participation.
10. Receipt of any blood/plasma products or immunoglobulin, from 60 days before study 
intervention administration, or planned receipt throughout the study.
11. Individuals who receive chronic treatment with immunosuppressive therapy, including 
cytotoxic agents, monoclonal antibodies, systemic corticosteroids, or radiotherapy, eg, for 
cancer or an autoimmune disease, from 60 days before study intervention administration 
or planned receipt throughout the study. If systemic corticosteroids (<20 mg/day of 
prednisone or equivalent) have been administered short term (<14 days) for treatment of 
an acute illness, participants should not be enrolled in the study until corticosteroid 
therapy has been discontinued for at least 28 days before study intervention 
administration. Inhaled/nebulized, intraarticular, intrabursal, or topical (skin or eyes) 
corticosteroid use is permitted.
Note: Participants with COPD or asthma can be enrolled if chronic corticosteroids do not 
exceed a dose equivalent to 10 mg/day of prednisone.
12. Current alcohol abuse or illicit drug use.
13. Current use of any prohibited concomitant medication(s) or those unwilling/unable to use 
a permitted concomitant medication(s). Refer to Section 6.10.
Prior/Concurrent Clinical Study Experience:
14. Participation in other studies involving investigational product(s) within 28 days prior to 
consent and/or during study participation.
Other Exclusions:
15. 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.

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5.3. Lifestyle Considerations
5.3.1. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant from the permitted list of contraception methods (see Appendix 3, Section 10.3) 
and will confirm that the participant has been instructed in its consistent and correct use. At 
time points indicated in the SoA, the investigator or designee will inform the participant of 
the need to use highly effective contraception consistently and correctly and document the 
conversation and the participant’s affirmation in the participant’s chart (participants need to 
affirm their consistent and correct use of at least 1 of the selected methods of contraception) 
considering that their risk for pregnancy may have changed since the last visit. In addition, 
the investigator or designee will instruct the participant to call immediately if the selected 
contraception method is discontinued or if pregnancy is known or suspected in the participant 
or partner.
5.4. Screen Failures
Screen failures are defined as 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.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened under a new participant number.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Administration of 
Study Intervention
The following conditions may allow a participant to be vaccinated once the conditions have 
resolved and the participant is otherwise eligible:

Current febrile illness (body temperature ≥38°C [≥100.4°F]) or other acute illness within 
48 hours before study intervention administration.

Receipt of any inactivated vaccine, licensed COVID-19 vaccines, or COVID-19 vaccines 
authorized for temporary or emergency use within 14 days or any live vaccine within 
28 days before study intervention administration.

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.

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6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
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.
For the purposes of this protocol, study intervention refers to RSVpreF and placebo 
(lyophilized cake containing excipients reconstituted in sterile water for injection).
Commercially available SIIV will be provided by the sponsor as a concomitant vaccine.
6.1. Study Intervention(s) Administered 
6.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine
Intervention Name
RSVpreF
Type
Vaccine
Dose Formulation
The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal 
amounts from virus subgroups A and B, in a lyophilized dosage form for 
reconstitution. The RSV study intervention will be 120 µg of the RSV prefusion F 
antigen. The study intervention is supplied as a lyophilized white cake in a 2-mL glass 
vial, with a 13-mm lyophilization stopper, aluminum overseal, and flip-off cap.
The study intervention will be reconstituted by a diluent consisting of sterile water in a 
PFS. The lyophilized cake contains excipients that, after reconstitution, will yield a 
solution as detailed in the IB.
The fill volume of the study intervention vial and diluent PFS are designed such that 
the intended vaccine dose is delivered by injecting the entire contents of the syringe.
Dosage Level(s)
120 µg RSVpreF by a single injection.
Route of 
Administration
IM injection into the deltoid muscle of the LEFT arm.
Use
Experimental
Sourcing
RSVpreF will be provided by the sponsor to each study site.
Packaging and 
Labeling
RSVpreF will be packaged within cartons labeled by Pfizer or its designee in 
accordance with current guidelines and applicable local and legal regulatory 
requirements.
Intervention Name
Placebo
Type
Placebo
Dose Formulation
The placebo is supplied as a lyophilized white cake in a 2-mL glass vial, with a 13-mm 
lyophilization stopper, aluminum overseal, and flip-off cap. It contains no active 
ingredients.
The placebo will be reconstituted by a diluent consisting of sterile water in a PFS. The 
lyophilized cake contains excipients that, after reconstitution, will yield a volume 
matching RSVpreF.
The fill volume of the placebo vial and diluent PFS are designed such that the intended 
vaccine dose is delivered by injecting the entire contents of the syringe.

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Intervention Name
Placebo
Route of 
Administration
IM injection into the deltoid muscle of the LEFT arm.
Use
Placebo control
Sourcing
Placebo will be provided by the sponsor to each study site.
Packaging and 
Labeling
The placebo will be packaged within cartons labeled by Pfizer or its designee in 
accordance with current guidelines and applicable local and legal regulatory 
requirements.
6.1.2. Concomitant Seasonal Inactivated Influenza Vaccine
Commercially available quadrivalent adjuvanted SIIV (if available), or an appropriate 
alternative SIIV for this older adult population, will be provided. Investigational sites will be 
notified which commercially available SIIV will be provided prior to the start of enrollment.
Pfizer will provide this vaccine; however, with approval by the sponsor, a site may 
independently procure the study-specific SIIV rather than receive shipment of SIIV from the 
sponsor. SIIV will be shipped and stored as per the commercial package insert and 
commercial label. Administration of SIIV will be recorded in the CRF and study records.
6.2. Administration
RSVpreF and placebo will be prepared and administered by a blinded site staff member by 
injecting the entire contents of the syringe into the LEFT deltoid muscle.
SIIV will be prepared and administered by injecting the entire contents of the syringe into the 
deltoid muscle of the RIGHT arm. No blinding is required for the preparation or 
administration of SIIV.
Administration is summarized below.
Table 1.
Vaccine Administration Group
Product Administered
Visit 1 Vaccination 1
Visit 2 Vaccination 2
Group 1
Coadministration 
Right deltoid muscle 
SIIV
Left deltoid muscle 
RSVpreF
Placebo
Group 2 
Sequential Administration 
Right deltoid muscle 
SIIV
Left deltoid muscle 
Placebo
RSVpreF
Abbreviation: SIIV = seasonal inactivated influenza vaccine.

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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.
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.
Study intervention administration details will be recorded on the CRF and pharmacy/study 
records.
6.3. Medical Devices
In this study, medical devices being deployed are for the reconstitution diluent for the study 
intervention. The study intervention supplies are provided in a kit that contains a vial of 
either RSVpreF or placebo lyophilized powder, a PFS containing sterile water, and a vial 
adapter. Instructions for their use are provided in the IPM.
Medical device deficiencies, including those resulting from malfunctions of the device, must 
be detected, documented, and reported by the study personnel throughout the study. Please 
refer to Section 8.3.9 for details.
6.4. Preparation, Handling, Storage, and Accountability

The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention.

Only 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.

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 IPM.

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
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the label.

Study interventions should be stored in their original containers.

See the IPM for storage conditions of the study intervention once reconstituted.

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.

Further guidance and information for the final disposition of unused study interventions 
are provided in the IPM. 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 IPM.
6.4.1. Preparation and Dispensing
See the IPM for instructions on how to prepare the study intervention for administration. 
Study intervention should be prepared and dispensed by an appropriately medically 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 preparation and dispensing.
6.5. Measures to Minimize Bias: Randomization and Blinding
6.5.1. Randomization to Study Intervention 
Randomization of participants to vaccine groups will proceed through the use of an IRT 
system. 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 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 participant number, randomization number, and DU or container number 
assigned. The confirmation report must be stored in the site’s files.
The study-specific IRT reference manual and IPM will provide the contact information and 
further details on the use of the IRT system.

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6.5.2. Blinding Arrangements
This study is double-blinded.
6.5.2.1. Blinding of Study Site Personnel
The participant, study coordinator, and all site staff will be blinded.
Please refer to the IPM for further details.
6.5.2.2. Blinding of the Sponsor
The majority of sponsor staff will be blinded to study intervention allocation. All laboratory 
testing personnel performing serological assays or diagnostic assays will remain blinded to 
the study intervention assigned/received throughout the study.
6.5.3. 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 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 
participant’s vaccine assignment unless this could delay further management of the 
participant. If a 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 IPM will provide the contact information and 
further details on the use of the IRT system.
6.6. Study Intervention Compliance
Participants will receive study intervention directly from the investigator or designee, under 
medical supervision. The date and time of administration will be recorded in the source 
documents and in the CRF. The study intervention identification details and study participant 
identification will be checked and confirmed at the time of and prior to administration by a 
second member of the study site staff who is not the person administering the vaccine.
The site will complete the required vaccine Preparation Record located in the IPM. The use 
of the Preparation Record is preferred, but it does not preclude the use of an existing 
appropriate clinical site documentation system. The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose. This may be used in place of the Preparation Record after 
approval from the sponsor and/or designee.
6.7. Dose Modification
Not applicable.

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6.8. Continued Access to Study Intervention After the End of the Study
No intervention will be provided to study participants at the end of their study participation.
6.9. 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.
There is no specific treatment for an overdose.
In the event of an overdose, the investigator should:

Contact the medical monitor within 24 hours.

Closely monitor the participant for any AEs/SAEs.

Document the quantity of the excess dose as well as the duration of the overdose in the 
CRF.

Overdose is reportable to Pfizer Safety only when associated with an SAE.
6.10. Concomitant Therapy
6.10.1. Prohibited Concomitant Vaccinations and Medications

Licensed or nonstudy investigational RSV vaccines are prohibited at any time prior to 
enrollment and thereafter during the course of the study.

Investigational vaccines and investigational drugs are prohibited within 28 days prior to 
enrollment and at any time during the study.
6.10.2. Withholding Periods for Concomitant Vaccinations and Medications
Unless considered medically necessary, the following restrictions apply to nonstudy licensed 
vaccines and medications as well as COVID-19 vaccines authorized for temporary or 
emergency use:

Nonstudy nonlive vaccines (including licensed or authorized COVID-19 vaccines) may 
not be given within 14 days before or after study intervention administration.

Nonstudy live vaccines should not be given within 28 days before or within 28 days after 
study intervention administration.

Systemic corticosteroids (≥20 mg/day of prednisone or equivalent) for ≥14 days should 
not be given within 28 days before study intervention administration through the 
conclusion of study participation.

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
Chronic systemic treatment with known immunosuppressant medications should not be 
given within 60 days before study intervention administration through the conclusion of 
study participation.

Blood/plasma products or immunoglobulin should not be given within 60 days before 
study intervention administration through the conclusion of study participation.

Prophylactic antipyretics and other pain medication to prevent symptoms associated with 
study intervention administration are not permitted.
6.10.3. Permitted Nonstudy Vaccines and Medications During the Study
The following restrictions apply to permitted vaccines and medications (except when they are 
considered medically necessary):

Nonstudy nonlive vaccines (including licensed or authorized COVID-19 vaccines) may 
be given starting 14 days after the Visit 2 study intervention administration.

Nonstudy live vaccines may only be given after study completion.

Inhaled/nebulized, intra-articular, intrabursal, or topical (eg, skin, eyes) corticosteroids 
are permitted. 

Chronic corticosteroids that do not exceed a dose equivalent to 10 mg/day of prednisone 
are permitted for participants with COPD or asthma

The use of antipyretics and other pain medication to treat symptoms associated with 
study intervention administration is permitted.

Medication other than that listed in Section 6.10.1 and Section 6.10.2, required for 
treatment of preexisting stable conditions, is permitted.
6.10.4. Recording Nonstudy Vaccinations and Concomitant Medications
The following concomitant medications and vaccinations will be recorded in the CRF:

All nonstudy vaccinations including COVID-19 vaccines, received from 28 days prior to 
study enrollment through conclusion of study participation.

Immunosuppressant medications, including monoclonal antibodies.

Systemic corticosteroids, ie, oral, IM, or IV. Do not record topical, ophthalmic, otic, 
inhaled, intra-articular, or intrabursal corticosteroids.

Blood/plasma products or immunoglobulin.

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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanently discontinuation of study intervention include the following: AEs, participant 
request, investigator request, protocol deviation, no longer meeting all the inclusion criteria, 
or meeting 1 or more exclusion criteria.
Discontinuation of study intervention does not represent withdrawal from the study. If study 
intervention is discontinued, the participant will remain in the study to be evaluated for 
safety. Participants who remain in the study for evaluation of safety will be contacted by 
telephone 1 month after their last study vaccination to record AEs.
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, posttreatment study follow-up, 
and/or future collection of additional information.
7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:

Refused further study procedures;

Lost to follow-up;

Death;

Study terminated by sponsor;

AEs;

Physician decision;

Protocol deviation;

Participant request.
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, he/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.

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If the participant withdraws from the study and also withdraws consent (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.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Vaccine SAE Reporting Form.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
Participants who withdraw after randomization will not be replaced.
7.2.1. 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 him or her or persons previously authorized by the participant to provide this 
information. 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 
posttreatment 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 participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to attend a required study visit:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible. Counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether 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.

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
Should the participant continue to be unreachable, he/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.
The date of birth will be collected to critically evaluate the immune response and safety 
profile by age.
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
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 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
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 study initiation.
8.1. Efficacy and/or Immunogenicity Assessments
8.1.1. Efficacy Assessments
Efficacy assessments are not applicable to this study.

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8.1.2. Immunogenicity Assessments
8.1.2.1. Blood Collection
Blood samples (approximately 30 mL per sample) for immunogenicity assessments will be 
collected from all enrolled participants just prior to each study vaccination at Visit 1 and 
Visit 2, and at Visit 3. The total blood sampling volume for individual participants in this 
study is approximately 90 mL across 2 months.
Instructions for the collection and handling of blood and serum samples will be provided in 
the laboratory manual. The date and time of each sample will be recorded.
The immunogenicity samples must be processed and shipped as indicated in the instructions 
provided to the investigator site to maintain sample integrity. Any deviations from the 
immunogenicity sample handling procedure (eg sample collection and processing steps, 
interim storage, or shipping conditions), including any actions taken, must be documented, 
and reported to the sponsor. On a case-by-case basis, the sponsor may make a determination 
as to whether sample integrity has been compromised.
8.1.2.2. RSV Vaccine Antibody Testing
Serum samples collected at all 3 visits will be assayed for RSV A and RSV B serum NTs
 
RSV A and RSV B serum NTs will be determined and reported as the NT.
 
 
Sample collection, processing, storage, and shipping information can be found in the 
laboratory manual. All assays will be performed by Pfizer and/or at a facility designated by 
Pfizer.
8.1.2.3. SIIV Immune Response Testing
HAI titers to the influenza strains in the SIIV administered will be determined on sera 
collected at Visits 1 and 2 (prior to and 1 month after SIIV administration).
H3N2-neutralizing antibody titers may be determined if the H3N2 strain in the SIIV fails to 
hemagglutinate or hemagglutinates via neuraminidase rather than hemagglutinin, which may 
invalidate the HAI assay for H3N2.
8.1.2.4. Exploratory Assays, Including Immunogenicity Assessments and Assay 
Development
Samples remaining after completion of the planned assays from blood draws may be used for 
additional vaccine and infectious disease-related research. Samples may also be used for 
assay development, standardization, qualification, and validation. This work is critical in the 
development, qualification, and validation of serological assays and is required by regulatory 
authorities for their use in the licensure of a vaccine.
CCI
CCI

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8.1.3. Biological Samples
Blood/serum 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 will be performed.
The participant may request that his/her 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 is performed.
8.2. Safety Assessments
Participants will be observed for 30 minutes after vaccination, and any reactions occurring 
during that time will be recorded as AEs.
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.
8.2.1. Physical Examinations
If the clinical assessment indicates that a physical examination is necessary to 
comprehensively evaluate the participant, a physical examination will be performed.
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Section 10.2) must be reported according to the processes in
Section 8.3.1 to Section 8.3.3.
8.2.2. Vital Signs
The participant’s body temperature will be measured prior to each vaccination.
8.2.3. Electronic Diary
Participants will be required to use an e-diary, installed on a provisioned device or as an 
application on a personal device, and will be asked to monitor and record local reactions, 
systemic events, and oral temperature each evening for 7 days following each vaccination 
(Day 1 through Day 7, where Day 1 is the day of vaccination). The e-diary allows recording 
of these assessments only within a fixed time window each day, thus providing the accurate 
representation of the participant’s experience at that time.

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Data on local reactions, systemic events, and oral temperature recorded in the e-diary will be 
transferred electronically to the e-diary vendor, where they will be available for review by 
investigators, their qualified designees, and sponsor staff at all times via a secure, restricted 
internet-based portal. At intervals agreed to by the vendor and Pfizer, these data will be 
transferred electronically to Pfizer for analysis and reporting. These data do not need to be 
recorded by the investigator in the CRF, except the following conditions:

If a participant withdraws because of prompted events recorded in the e-diary, the 
event(s) should be recorded on the AE page of the CRF, regardless of whether the 
investigator considers the event(s) to be clinically significant.

The investigator or designee must obtain stop dates for any reactions ongoing on the last 
day that the e-diary was completed. The stop dates should be documented in the source 
documents and the information entered in the CRF. In the event the reaction is ongoing at 
the end of the study, the reaction will be marked as ongoing.
Investigators (or appropriately qualified designees) are required to review the e-diary data 
online at frequent intervals to evaluate participant compliance and safety. These 
prospectively collected occurrences of local reactions and systemic events will be graded as 
described in Table 2, Table 3, and Table 4.
8.2.3.1. Local Reactions – Reactogenicity
Assessment of local reactions applies to both Visit 1 (RSV/placebo administration, left 
deltoid) and Visit 2 (RSV/placebo administration, left deltoid). Local reactions at the SIIV 
injection site (right deltoid) will not be recorded in the e-diary.
Following both Visit 1 and Visit 2 vaccinations (on Days 1 through 7, where Day 1 is the day 
of each vaccination), the participants will be asked to assess redness, swelling, and pain at the 
LEFT deltoid injection site and to record the symptoms in the e-diary or personal device, in 
the evening.
Redness and swelling will be measured by the participant and recorded in measuring device 
units (range: 1 to 21 and >21; an entry in the e-diary of 21 will denote ≥21) and then 
categorized during analysis as mild, moderate, or severe based on the grading scale in
Table 2. Measuring device units can be converted to centimeters according to the following 
scale: 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 Table 2.
If a severe (Grade 3) local reaction is reported in the e-diary, a telephone call with the 
participant should be made to ascertain further details and determine whether a site visit is 
clinically indicated.

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Only an investigator or a qualified designee is able to classify a participant’s local reaction as 
Grade 4, after clinical evaluation of the participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or, in the case of pain at the 
injection site only, contact with the participant. If a participant experiences a Grade 4 local 
reaction, the investigator must immediately notify the sponsor. A Grade 4 reaction will be 
collected as an AE on the CRF. The event will be graded using the AE intensity grading scale
(Section 10.2.3).
If a local reaction persists beyond the end of the 7-day e-diary period, the participant will be 
requested to report that information and/or any new AEs that develop to the investigator. The 
investigator will enter this additional information in the participant’s source notes and CRF.
Table 2.
Grading Scale for Local Reactions
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Redness
2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
10 cm 
(>20 measuring 
device units)
Necrosis or 
exfoliative dermatitis
Swelling
2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
10 cm 
(20 measuring 
device units)
Necrosis
Pain 
(at the injection 
site)
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room visit 
or hospitalization for 
severe pain at the 
injection site
a.
Only an investigator or qualified designee is able to classify a participant’s local reaction as Grade 4, 
after clinical evaluation of the participant or documentation from another medically qualified source 
(eg, emergency room or hospital record) or, in the case of pain at the injection site only, contact with the 
participant. Grade 4 local reactions will be collected on the AE case report form and assessed by the 
investigator using the AE intensity grading scale provided in Section 10.2.3.
8.2.3.2. Systemic Events
Following both Visit 1 and Visit 2 vaccinations (Day 1 through Day 7, where Day 1 is the 
day of each vaccination), participants will be asked to assess fatigue, headache, nausea, 
vomiting, diarrhea, muscle pain, and joint pain and to record the symptoms in the e-diary that 
evening. The symptoms will be assessed by the participant according to Table 3.
If a severe systemic event is reported in the e-diary, a telephone call with the participant 
should be made to ascertain further details and determine whether a site visit is clinically
indicated.

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Only an investigator or qualified designee is able to classify a participant’s systemic event as 
Grade 4, after clinical evaluation of the participant or documentation from another medically 
qualified source (eg, emergency room or hospital record) or contact with the participant. If a 
participant experiences a Grade 4 systemic event, the investigator must immediately notify 
the sponsor. Grade 4 reactions will be collected as an AE on the CRF and graded using the 
AE intensity grading scale (Section 10.2.3).
Further, if a systemic event persists beyond the end of the 7-day e-diary period, the 
participant will be requested to report that information and/or any new AEs that develop to 
the investigator. The investigator will enter this additional information in the participant’s 
source notes and CRF.
Table 3.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fatigue
(= tiredness)
Does not interfere 
with activity
Some interference
with activity
Prevents daily 
routine activity
Emergency room visit or 
hospitalization for severe 
fatigue
Headache
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room visit or 
hospitalization for severe 
headache
Vomiting
1 to 2 times in 
24 hours
2 times in 
24 hours
Requires intravenous 
hydration
Emergency room visit or 
hospitalization for severe 
vomiting
Nausea
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room visit or 
hospitalization for severe 
nausea
Diarrhea
2 to 3 loose stools in 
24 hours
4 to 5 loose stools 
in 24 hours
6 or more loose 
stools in 24 hours
Emergency room visit or 
hospitalization for severe 
diarrhea
Muscle pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room visit or 
hospitalization for severe 
muscle pain
Joint pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room visit or 
hospitalization for severe 
joint pain
a.
Only an investigator or qualified designee is able to classify a participant’s systemic event as Grade 4, 
after clinical evaluation of the participant or documentation from another medically qualified source 
(eg, emergency room or hospital record) or contact with the participant. Grade 4 systemic reactions will 
be collected on the AE case report form and assessed by the investigator using the AE intensity grading 
scale as detailed in Section 10.2.3.

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8.2.3.3. Fever Monitoring
A digital thermometer will be given to the participant with instructions on how to measure 
oral temperature at home. Temperature will be collected in the evening for 7 days following 
each vaccination (Day 1 through Day 7, where Day 1 is the day of each vaccination) and at 
any time during the 7 days following vaccination that fever is suspected.
Fever is defined as an oral temperature of ≥38.0°C (≥100.4°F). The highest temperature for 
each day will be recorded in the e-diary, where possible. Temperatures recorded in degrees 
Fahrenheit will be programmatically converted to degrees Celsius and then categorized 
according to the ranges shown in Table 4 during analysis.
In the event of a fever on the last day the diary was completed, temperature will be measured 
daily until fever has resolved (1 day of temperature <38.0°C [<100.4°F]) in order to collect a 
stop date in the CRF.
If a fever of ≥39.0°C (≥102.1°F) is reported in the e-diary, a telephone contact with the 
participant 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 
participant’s fever as >40.0°C (>104.0°F). If a participant experiences a confirmed fever 
>40.0°C (>104.0°F), the investigator must immediately notify the sponsor. Grade 4 fevers 
will be collected on the AE CRF and assessed by the investigator using the AE intensity 
grading scale as detailed in Section 10.2.3.
Table 4.
Ranges for Fever
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4a
Fever
≥38.0°C to 38.4°C
(100.4-101.1°F)
38.4°C to 38.9°C
(101.2-102.0°F)
38.9°C to 40.0°C
(102.1-104.0°F)
40.0°C
(104.0°F)
a.
Only an investigator or qualified designee is able to classify a participant’s fever as Grade 4, after clinical 
evaluation of the participant, documentation from another medically qualified source (eg, emergency 
room or hospital record), or contact with the participant. Grade 4 fevers will be collected on the AE case 
report form and assessed by the investigator using the AE intensity grading scale as detailed in 
Section 10.2.3.
8.2.4. Clinical Safety Laboratory Assessments 
Clinical safety laboratory assessments will not be collected in this study.
8.2.5. Pregnancy Testing
Not applicable.
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 2.

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The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 5. Device deficiencies are covered in Section 8.3.9.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc).
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 (Section 7).
During the active collection period as described in Section 8.3.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through to study 
completion (Visit 3).
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.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
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 permanently discontinues or temporarily discontinues from the study 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 information on 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 or withdrawn early from 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.

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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 immediately 
upon awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 2. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on 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.
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4.
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 or 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.
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 toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.

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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. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure.
Any such exposure to the study intervention under study is reportable to Pfizer Safety within 
24 hours of investigator awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female is found to be pregnant while being exposed or having been exposed to study 
intervention due to environmental exposure. Below are examples of environmental EDP:

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by injection, ingestion, inhalation, or 
skin contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by injection, ingestion, inhalation, or skin contact then exposes his 
female partner prior to or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy).

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
If EDP occurs in a participant or participant’s partner, the investigator must report this 
information to Pfizer Safety on the Vaccine SAE Reporting Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the pregnancy 
will be collected after the start of study intervention and until 28 days after study 
intervention administration (Visit 3).

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the Vaccine SAE Reporting Form and EDP 
Supplemental Form. 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), 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). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.

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8.3.5.2. Exposure During Breastfeeding
EDB occurs when: 

A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental EDB is a 
female family member or healthcare provider who reports that she is breastfeeding after 
having been exposed to the study intervention by injection, ingestion, inhalation, or skin 
contact.
The investigator must report EDB 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 EDB 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 EDB.
8.3.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the Vaccine SAE Reporting Form, regardless 
of whether there is an associated SAE. Since the information about the occupational exposure 
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 must be 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
Not applicable.
8.3.8. Adverse Events of Special Interest
Not applicable.

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8.3.9. Medical Device Deficiencies
Medical devices are being provided for use in this study for the purposes of administering the 
study intervention and include a PFS and vial adapter. To fulfill regulatory reporting 
obligations worldwide, the investigator is responsible for the detection and documentation of 
events meeting the definitions of device deficiency that occur during the study with such 
devices.
The definition of a medical device deficiency can be found in Appendix 5.
Note: AEs and/or SAEs that are associated with a medical device deficiency will follow the 
same processes as other AEs or SAEs, as outlined in Section 8.3.1 through 8.3.4 and 
Appendix 2 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies that result in an incident will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
Importantly, reportable device deficiencies are not limited to problems with the device itself 
but also include incorrect or improper use of the device and even intentional misuse, etc.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such deficiency is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 5.
8.3.9.2. Follow-Up of Medical Device Deficiencies
Follow-up applies to all participants, including those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.9.3. Prompt Reporting of Device Deficiencies to the Sponsor
When a device deficiency occurs: 

The investigator notifies the sponsor by telephone or email within 1 business day of 
determining that the incident meets the protocol definition of a medical device 
deficiency.

The device deficiency must be recorded on the Medical Device Complaint Form.

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
If an AE (either serious or nonserious) associated with the device deficiency occurs, then 
the AE must be entered into the AE section of the CRF.

If an SAE associated with the device deficiency is brought to the attention of the 
investigator, the investigator must immediately notify Pfizer Safety of the SAE 
(see Section 8.3.1.1). All relevant details related to the role of the device in the 
event must be included in the Vaccine SAE Reporting Form as outlined in
Sections 8.3.1.1 and 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
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.

The administration of expired study intervention.

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
The administration of an incorrect study intervention.

The administration of an incorrect dosage.

The administration by an incorrect route.

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.
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.
8.4. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.5. Genetics
Genetics are not evaluated in this study.
8.6. Biomarkers
Biomarkers are not evaluated in this study.
8.7. Immunogenicity Assessments
Immunogenicity assessments are described in Section 8.1.2.
8.8. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.

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8.9. Study Procedures
8.9.1. Visit 1 – Vaccination 1 (Clinic, Day 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the participant. Each signature on the 
ICD must be personally dated by the signatory. The investigator or his or her designee will 
also sign and date the ICD. A copy of the signed and dated ICD must be given to the 
participant. The source data must reflect that the informed consent was obtained before 
participation in the study.
Study procedures should be conducted in a stepwise manner as ordered below: 

Obtain written informed consent either in electronic or hard copy format from the 
participant before performing any study-specific procedures.

Assign a single participant identifier using the IRT system.

Obtain and record the participant demography (including complete date of birth 
[dd-Mmm-YYYY], sex, race, racial designation, and ethnicity). The full date of birth will 
be collected to critically evaluate the immune response and safety profile by age.

Obtain and record any medical history of clinical significance.

Record current or former tobacco use.

Perform a clinical assessment. If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination and record any findings in the source documents and, if clinically 
significant, record on the medical history CRF.

Measure and record prevaccination body temperature.

Obtain details of any nonstudy vaccinations as described in Section 6.10.

Review concomitant medication use as described in Section 6.10.

Ensure and document that all 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. If delay criteria are met, reschedule the Visit 1 blood draw and 
randomization/vaccination for a later date.

Prior to vaccination, collect a blood sample of approximately 30 mL for antibody 
assessment.

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
Obtain the participant’s randomization number and study intervention kit number using 
the IRT system. Refer to the IRT manual for further instructions on this process.

Issue a measuring device to measure local reactions at the LEFT injection site and a 
thermometer for recording oral temperature.

Explain the e-diary technologies available for this study (Section 8.2.3), and assist the 
participant in downloading the e-diary application onto the participant’s own device or if 
required, issue a sponsor-provisioned e-diary.

Work with the participant to set up the device/e-diary and provide training on daily 
e-diary completion. Ask the participant to complete the e-diary each evening between 
4:00 PM and midnight, starting on Day 1 and completing on Day 7, where Day 1 is the 
day of Vaccination 1.

Qualified site staff member(s) will administer the SIIV into the deltoid muscle of the 
RIGHT arm and the study intervention into the deltoid muscle of the LEFT arm.

Observe the participant for any acute reactions for at least 30 minutes after study 
intervention administration. Record any acute reactions, including the time of onset, in 
the participant’s source documents, on the AE page of the CRF, and on the Vaccine SAE 
Reporting Form if applicable.

Discuss contraceptive use where applicable and as described in Section 10.3.4.

Provide participant with an ECC and instruct the participant on its use.

Ask the participant to contact the site staff or investigator immediately if he/she 
experiences any of the following reactions from Day 1 to Day 7 after Vaccination 1 
(where Day 1 is the day of Vaccination 1) to determine if an unscheduled reactogenicity 
visit is required (Section 8.9.4).

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the LEFT injection site measuring >20 measuring device units 
(greater than 10 cm).

Severe pain at the LEFT injection site.

Any severe systemic event.

Any emergency room attendance or hospitalization.

Advise the participant that study staff may make contact to obtain additional information 
on events entered in the e-diary.

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
Advise the participant to inform the study staff of any AEs and SAEs that occur for the 
duration of the study as described in Section 8.3.1.

Request that the participant bring the completed e-diary to the next visit.

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 completes the study intervention accountability records.

Following vaccination, the investigator or appropriately qualified designee reviews the 
daily e-diary data online to evaluate participant compliance and as part of the ongoing 
safety review.
8.9.2. Visit 2 – Vaccination 2 (Clinic, 28 to 35 Days After Visit 1)

Record details of any nonstudy vaccinations and concomitant medications as described in 
Section 6.10.4.

Record AEs and SAEs as described in Section 8.3.1 Obtain and record any missing AE 
stop dates.

Review the participant’s e-diary data. Collect stop dates of any ediary events ongoing on 
the last day that the e-diary was completed and record stop dates in the CRF.

Obtain the participant’s body temperature.

Ensure that none of the temporary delay criteria are met (see Section 5.5).

Prior to Vaccination 2, collect a blood sample of approximately 30 mL for antibody 
assessment.

Qualified site staff member(s) will administer a single dose of study intervention into the 
deltoid muscle of the LEFT arm.

Observe the participant for any acute reactions for at least 30 minutes after study 
intervention administration. Record any acute reactions, including the time of onset, in 
the participant’s source documents, on the AE page of the CRF, and on the Vaccine SAE 
Reporting Form if applicable.

Discuss contraceptive use (where applicable) and as described in Section 10.3.4.

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
Confirm that the e-diary is set up for Vaccination 2 and review instructions, if necessary. 
Ask the participant to complete the e-diary from Day 1 to Day 7, with Day 1 being the 
day of Vaccination 2. Provide thermometer, measuring device, or ECC, if needed.

Ask the participant to contact the site staff or investigator immediately if he/she 
experiences any of the following reactions from Day 1 to Day 7 to determine if an 
unscheduled reactogenicity visit is required (Section 8.9.4) 

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the LEFT injection site measuring >20 measuring device units 
(greater than 10 cm).

Severe pain at the LEFT injection site.

Any severe systemic event.

Any emergency room attendance or hospitalization

Advise the participant that study staff may make contact to obtain additional information 
on events entered in the e-diary.

Advise the participant to inform the study staff of any AEs and SAEs that occur for the 
duration of the study as described in Section 8.3.1.

Request that the participant brings the completed e-diary to the next visit.

Schedule an appointment for the participant to return for the final study visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs and the 
dispenser/administrator completes the study intervention accountability records.

Following vaccination, the investigator or appropriately qualified designee reviews the 
daily e-diary data online to evaluate participant compliance and as part of the ongoing 
safety review.
8.9.3. Visit 3 Follow-Up After Vaccination 2 (Clinic, 28 to 35 Days After Visit 2)

Obtain details of any nonstudy vaccinations as described in Section 6.10.

Review concomitant medication use as described in Section 6.10.

Collect a blood sample of approximately 30 mL for antibody assessment.

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
Review the participant’s e-diary data. Collect stop dates of any ediary events ongoing on 
the last day that the e-diary was completed and record stop dates in the CRF. Collect the 
sponsor-provisioned e-diary.

Record AEs and SAEs as described in Section 8.3.1. Obtain and record any missing AE 
stop dates.

Complete the source documents.

The investigator or an authorized designee completes the CRF.
8.9.4. Unscheduled Reactogenicity Visits for a Grade 3 or Suspected Grade 4 Reaction
If a severe local reaction (Section 8.2.3.1), severe systemic event (Section 8.2.3.2), or fever 
≥39.0°C (≥102.1°F) (Section 8.2.3.3) is reported in the e-diary, a telephone contact with the 
participant should occur to ascertain further details and determine whether a site visit is 
clinically indicated. If a suspected Grade 4 local reaction, systemic event, or fever is reported 
in the reactogenicity e-diary, a telephone contact or site visit should occur to confirm whether 
the event meets the criteria for Grade 4.
A site visit or referral to a healthcare facility should be scheduled as soon as possible to 
assess the extent of the reaction, unless:

The participant is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or

The participant recorded an incorrect value in the e-diary (confirmation of an e-diary data 
entry error), or

The investigator or appropriate designee determines that an unscheduled visit is not 
required.
This contact will be recorded in the participant’s source notes and in the CRF.
If the participant is unable to attend the unscheduled visit, or the principal investigator or 
authorized designee determined it was not needed, any ongoing local reactions/systemic 
events must be assessed at the next study visit.
The reactogenicity events should be assessed by the investigator or a medically qualified 
member of the site staff, such as a study physician or a study nurse, as applicable to the 
investigator’s local practice or healthcare facility, who will:

Measure body temperature and record any fever (Table 4).

If present, measure the minimum and maximum diameters of redness at the LEFT
injection site.

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
If present, measure the minimum and maximum diameters of swelling at the LEFT
injection site.

Assess any LEFT injection site pain in accordance with the reactogenicity grading scale 
provided in Table 2.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Table 3.

Assess for other findings associated with the reaction and record on the AE CRF, if 
appropriate.

Record AEs and SAEs as described in Section 8.3.1.

Complete the participant’s source documents.

The investigator or an authorized designee completes the unscheduled visit assessment 
CRF.
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in the 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. Statistical Hypotheses
9.1.1. Estimands
The estimands corresponding to each primary, secondary, and exploratory objectives are 
described in Section 3.
The estimands to evaluate the immunogenicity objectives are based on the evaluable 
immunogenicity population (Section 9.2). These estimands estimate the vaccine effect in the 
hypothetical settings where participants follow the study schedules and protocol requirements 
as directed. Missing immunogenicity results will not be imputed, as MCAR is assumed.
In the primary safety objective evaluations, completely missing reactogenicity e-diary data 
will not be imputed. Missing AE dates will be imputed according to Pfizer safety rules. No 
other missing information will be imputed in the safety analysis.

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9.1.2. Statistical Hypotheses
9.1.2.1. Statistical Hypothesis for Primary RSV Immunogenicity
The primary immunogenicity objective on immune response elicited by RSVpreF will be 
evaluated by the following hypothesis for both RSV A and RSV B as measured by NT:
H01: ln(μ1) – ln(μ2) ≤ ln(0.667)
where ln(0.667) corresponds to a 1.5-fold margin for noninferiority and ln(µ1) and ln(µ2) are 
the natural log of the geometric mean of NT at 1 month after vaccination with RSVpreF for 
the coadministration group (Visit 2) and the sequential-administration group (Visit 3), 
respectively. Noninferiority will be declared if the lower limit of the 2-sided 95% CI for the 
GMR (coadministration group to sequential-administration group) is >0.667 for both RSV A 
and RSV B NTs.
9.1.2.2. Statistical Hypothesis for SIIV Immunogenicity
The primary immunogenicity objective on immune response elicited by SIIV will be 
evaluated by the following hypothesis for each strain included in SIIV:
H02: ln(μ1) – ln(μ2) ≤ ln(0.667)
where ln(0.667) corresponds to a 1.5-fold margin for noninferiority, and ln(µ1) and ln(µ2) 
are the natural log of the geometric mean of the strain-specific HAI titers 
(or H3N2-neutralizing antibody titers if interpretable H3N2-HAI titers cannot be obtained) 
1 month after vaccination with SIIV for the coadministration group and the 
sequential-administration group, respectively. Noninferiority will be declared for an 
influenza strain if the lower limit of the 2-sided 95% CI for the GMR (coadministration 
group to sequential-administration group) is >0.667. The primary SIIV immunogenicity 
objective of the study will be achieved if the noninferiority is met for each of the 
4 influenza strains.
9.1.3. Multiplicity Adjustment
No multiplicity adjustment will be applied for this study. The primary objectives of 
noninferiority will be achieved only if the 1.5-fold equivalence criterion is met for each strain 
included in SIIV and for both RSV A and RSV B antigens simultaneously. Each of the 
6 statistical tests (4 from the SIIV objective and 2 from the RSV objective) will use a 2-sided 
alpha level of 0.05.

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9.2. Analysis Sets
Table 5.
Analysis Sets
Analysis Set
Description
Population analysis set
Enrolled
All participants who have a signed ICD.
Randomized population
All participants who are assigned a randomization number in the IRT system.
Safety population
All enrolled participants who receive the study intervention.
Defined analysis sets
Evaluable RSV 
immunogenicity population 
All participants who meet the following criteria:

Are eligible for the study;

Received the study interventions to which they were randomized at both 
Visit 1 and Visit 2;

Had the 1-month postvaccination blood collection within an appropriate 
window (Visit 2 for the coadministration group and Visit 3 for the 
sequential-administration group);

Had no major protocol violations from randomization through the 1-month 
postvaccination blood draw;

Had at least 1 valid and determinate assay result 1 month after vaccination.
Evaluable SIIV
immunogenicity population 
All participants who meet the following criteria:

Are eligible for the study;

Received the study interventions to which they were randomized in 
addition to SIIV at Visit 1;

Had the 1-month postvaccination blood collection within an appropriate 
window (Visit 2);

Had no major protocol violations from randomization through the 1-month 
postvaccination blood draw;

Had at least 1 valid and determinate assay result 1 month after vaccination.
mITT immunogenicity 
population 
All participants who were randomized and had at least 1 valid and determinate 
assay result at any time point after receiving study intervention.
9.3. 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.
9.3.1. General Considerations
CIs for all endpoints in the statistical analysis will be presented as 2-sided at the 95% level 
unless specified otherwise.

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For all the immunogenicity endpoints, the analysis will be based on the evaluable 
immunogenicity populations. An additional analysis will be performed based on the mITT 
population if there is a large enough difference in sample size between the mITT population 
and the evaluable immunogenicity population(s). Participants will be summarized according 
to the group (coadministration group and sequential-administration group) to which they 
were randomized.
The safety analyses will be based on the safety population. Participants will be summarized 
by group according to the study intervention they actually received.
9.3.1.1. 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. The 95% CI for 
percentage, and for difference in percentages, may also be presented where appropriate.
The exact 95% CI for binary endpoints for each group will be computed using the 
F-distribution (Clopper-Pearson).15
The 95% CI for the difference in the proportions will be computed using the Miettinen and 
Nurminen16 method. The 95% CI will be presented in terms of percentage.
9.3.1.2. Analyses for Continuous Data
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
SD, minimum, and maximum.
9.3.1.2.1. Geometric Means
Continuous immunogenicity endpoints will be logarithmically transformed for analysis. 
Geometric means and associated 2-sided 95% CIs will be derived by calculating group 
means and CIs on the natural log scale based on the t-distribution, and then exponentiating 
the results.
9.3.1.2.2. Geometric Mean Fold Rises
GMFRs will be calculated as the group mean of the difference of logarithmically transformed 
assay results (later time point minus earlier time point) and exponentiating the mean. GMFRs 
are limited to participants with nonmissing values at both time points. The associated 2-sided 
95% CIs will be obtained by constructing CIs using Student’s t distribution for the mean 
difference on the logarithm scale and exponentiating the confidence limits.
9.3.1.2.3. Geometric Mean Ratios
The GMRs will be calculated as the mean of the difference of logarithmically transformed 
assay results between 2 groups (coadministration group to sequential-administration group) 
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.

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9.3.1.2.4. 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 the line first going down and then to the right to 
the next assay value.
9.3.2. Primary Endpoint(s)
Table 6.
Primary Endpoint Analyses
Endpoint
Statistical Analysis Methods
Immunogenicity

GMRs of RSV NTs in the coadministration group to the sequential-administration 
group for RSV A and RSV B at 1 month after vaccination with RSVpreF will be 
provided along with the associated 2-sided 95% CIs (Section 9.3.1.2.3).

GMRs of strain-specific HAI titers (or H3N2-neutralizing antibody titers if 
interpretable H3N2-HAI titers cannot be obtained) in the coadministration group to the 
sequential-administration group at 1 month after vaccination with SIIV will be 
provided along with the associated 2-sided 95% CIs (Section 9.3.1.2.3).

Using a 1.5-fold equivalence margin, equivalence will be declared if the lower bound 
of the 2-sided 95% CI for the GMR is greater than 0.667 for all 4 SIIV strains and for 
both RSV A and RSV B antigens.
Safety

Descriptive statistics will be provided for each reactogenicity endpoint for RSVpreF 
and placebo at both vaccination visits. Local reactions (redness, swelling and pain at 
the injection site) and systemic events (fever, fatigue, headache, nausea, vomiting, 
diarrhea, muscle pain, and joint pain) from Day 1 through Day 7 after 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 (Section 9.3.1.1).

AEs and SAEs will be categorized according to MedDRA terms. All of the AEs will 
be descriptively summarized by vaccine group within 1 month after each vaccination.

A 3-tier approach will be used to summarize AEs. 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; there is no 
Tier 1 event identified for RSVpreF at this stage; (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; (3) Tier 3 events are those that are neither Tier 1 nor Tier 2 
events. For both Tier 1 and Tier 2 events, the 95% CIs for the difference in the 
percentage of participants reporting the events between the RSVpreF group and the 
placebo group will be calculated using the test statistic proposed by Miettinen and 
Nurminen16; in addition, for Tier 1 events, the asymptotic p-values will also be 
presented for the difference in the percentage of participants reporting the events, 
based on the same test statistic and under the assumption that the test statistic is 
asymptotically normally distributed. For Tier 3 events, counts and percentages for 
each vaccine group will be provided.

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9.3.3. Secondary Endpoint(s)
Table 7.
Secondary Endpoint Analyses
Endpoint
Statistical Analysis Methods
Immunogenicity

Geometric means (at each applicable visit) and GMFRs (from before to each 
applicable time point after RSVpreF vaccination) of the RSV NTs and the 
associated 2-sided 95% CIs will be provided for each vaccine group 
(coadministration group vs sequential-administration group) for RSV A and RSV B 
(Sections 9.3.1.2.1 and 9.3.1.2.2).

Geometric means and GMFRs of strain-specific HAI titers or H3N2-neutralizing 
antibody titers (if interpretable H3N2-HAI titers cannot be obtained) before 
vaccination and 1 month after vaccination with SIIV and the associated 2-sided 95% 
CIs will be summarized similarly.
9.3.4. Exploratory Endpoint(s)
Table 8.
Exploratory Endpoint Analyses
Endpoint
Statistical Analysis Methods
Immunogenicity

 

For each HAI strain, counts and percentages of participants with seroprotection 
(defined as strain-specific HAI titers ≥1:40) before vaccination and 1 month after 
vaccination with SIIV will be provided for each vaccine group, along with the 
associated Clopper-Pearson 95% CIs.

Seroconversion is defined as an HAI titer <1:10 before SIIV vaccination and an HAI 
titer ≥1:40 1 month after SIIV vaccination or an HAI titer ≥1:10 before vaccination 
and a minimum 4-fold rise in HAI titer 1 month after SIIV vaccination. For each HAI 
strain, counts and percentages of participants with strain-specific HAI titer 
seroconversion 1 month after vaccination with SIIV, along with the associated 
Clopper-Pearson 95% CIs, will be provided for each vaccine group.

Seroprotection and seroconversion for NTs will be defined in the SAP, and the 
analysis will be similar to HAI.
9.4. Interim Analyses
No formal interim analysis will be conducted for this study. Only 1 analysis will be 
performed at the completion of the study.
9.5. Sample Size Determination
Table 9 presents the power to demonstrate that the immune responses induced by 
coadministration of RSVpreF and SIIV are noninferior to the administration of RSVpreF or 
SIIV alone.
CCI

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For both NT and HAI assay results, it is assumed that true ratios of the coadministration 
group to the sequential-administration group are not larger than 0.9 (or -0.105 with the
natural log scale). The SDs of the log titers are based on Study C3671001 data.
Considering this is a short study among older adults, it is reasonable to assume a 
7-8% nonevaluable rate; consequently, enrolling approximately 1400 participants in the 
study will provide a sample size of approximately 1300 participants to be included in the 
evaluable population analysis. With 650 evaluable participants per vaccine group and the 
above assumptions, the power is 81.6% to declare noninferiority for all 4 strains included in 
SIIV and both RSV A and RSV B. Power was calculated with PROC POWER in SAS using 
the TWOSAMPLEMEANS statement.
Table 9.
Sample Size Determination
Antigen
Common SD 
(Log e Scale)a
Difference
(Log e Scale)
Noninferiority 
Margin
Power to Declare 
Noninferiority
(1-Sided Alpha = 0.025)
RSV A
1.3
0.105
1.5-fold
98.6%
RSV B
1.4
0.105
1.5-fold
97.1%
H1N1
1.3
0.105
1.5-fold
98.6%
H3N2
1.7
0.105
1.5-fold
88.9%
B Strain 1
1.3
0.105
1.5-fold
98.6%
B Strain 2
1.3
0.105
1.5-fold
98.6%
Overall power to reject all 6 tests
81.6%
a.
The reference study is C3671001. The maximum SD across all age/vaccine groups was used for each 
antigen/strain.

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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, 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.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation 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 GCP guidelines, the IRB/EC, European Regulation 
536/2014 for clinical studies (if applicable), European MDR 2017/745 for clinical 
device research (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.

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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the 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, including the 
risks and benefits, 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, privacy, and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data.
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.

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Participants must be reconsented to the most current version of the IRB/EC-approved ICD(s) 
during their participation in the study as required per local regulations.
A copy of the ICD(s) must be provided to the participant.
Participants who are rescreened may be required to sign a new ICD as per IRB, local 
regulations, etc.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password-protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site 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 his or her actual identity and medical record ID. 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. Committees Structure
10.1.5.1. Data Monitoring Committee
This study will not use a DMC.
10.1.6. 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.
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.

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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 EU 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 Jan 2015 and applications for 
line extensions and for new indications submitted via the centralized procedure since 
01 Jul 2015.
Data sharing
Pfizer provides researchers secure access to participant-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 data from these trials available 
24 months after study completion. Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.

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10.1.7. 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.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
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.
QTLs are predefined parameters that are monitored during the study. Important deviations 
from the QTLs and any remedial actions taken will be summarized in the clinical study 
report.
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, including definition of study-critical data items and 
processes (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, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.

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The investigator(s) will notify the sponsor or its agents immediately of any regulatory retain 
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.
10.1.8. 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 and its origin can be found in the monitoring plan, 
which is maintained by the sponsor.
Description of the use of the computerized system is documented in the data management 
plan, which is maintained by the sponsor.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
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 guidelines, and all applicable regulatory requirements.
10.1.9. 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.

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The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/EC 
or local health authorities, the sponsor's procedures, or the ICH 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.
10.1.10. 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.

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Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements.
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.11. 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/study portal or other electronic system.
To facilitate access to appropriately qualified medical personnel for study-related medical 
questions or problems, participants are provided with an ECC at the time of informed 
consent. The ECC contains, at a minimum, (a) protocol and study intervention identifiers, 
(b) participant’s study identification number, (c) site emergency phone number active 
24 hours/day, 7 days per week, and (d) Pfizer Call Center number.
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. The Pfizer Call Center number should only be 
used when the investigator and site staff cannot be reached. The Pfizer Call Center number is 
not intended for use by the participant directly; if a participant calls that number directly, he 
or she will be directed back to the investigator site.

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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting
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 an 
increase in frequency and/or intensity of the condition.

New condition detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE or SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.

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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that 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 an SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed below:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE.

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An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed below:

Results in persistent or significant 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), that may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
d. Is a congenital anomaly/birth defect
e.
Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or nonpathogenic
The event may be suspected from clinical symptoms or laboratory findings indicating 
an infection in a participant 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.
f.
Other situations:

Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant medical 
events that 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.

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10.2.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period 
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs on the Vaccine SAE Reporting Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; 
(2) nonserious AEs; and (3) exposure to the study intervention under study during 
pregnancy or breastfeeding, and 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 
during pregnancy or 
breastfeeding.
All AEs or SAEs 
associated with EDP or 
EDB.
Note: Instances of EDP 
or EDB not associated 
with an AE or SAE are 
not captured in the CRF.
All instances of EDP are 
reported (whether or not there is 
an associated SAE).*
All instances of EDB are 
reported (whether or not there is 
an associated SAE).**
Environmental or 
occupational exposure to 
the product under study to 
a non-participant (not 
involving EDP or EDB).
None. Exposure to a 
study nonparticipant is 
not collected on the CRF.
The exposure (whether or not 
there is an associated AE or 
SAE) must be reported.***
*
EDP (with or without an associated AE or SAE): any pregnancy information is reported to Pfizer Safety 
using the Vaccine SAE Reporting Form and EDP Supplemental Form; if the EDP is associated with an 
SAE, then the SAE is reported to Pfizer Safety using the Vaccine SAE Reporting Form.
**
EDB is reported to Pfizer Safety using the Vaccine SAE Reporting Form, which would also include 
details of any SAE that might be associated with the EDB.
*** Environmental or occupational exposure: AEs or SAEs associated with occupational exposure are 
reported to Pfizer Safety using the Vaccine SAE Reporting Form.

When an AE or 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.

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
The investigator will then record all relevant AE or 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 or 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 or SAE.
Assessment of Intensity
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.
Assessment of Causality
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE or SAE. The investigator will use clinical judgment to 
determine the relationship.
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.

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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 or SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE or SAE and has provided an assessment of causality.
There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important 
that the investigator always make an assessment of causality for every event before 
the initial transmission of the SAE data to the sponsor.
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
If the investigator does not know whether or not the 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 submitted documents.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.

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10.2.4. 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) to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data become 
available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
off-line, then the site can report this information on a paper SAE form (see next section) 
or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.

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10.3. Appendix 3: Contraceptive and Barrier Guidance 
10.3.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent.
OR

Must agree to use contraception/barrier as detailed below:

Agree to use a male condom when having sexual intercourse with a woman of 
childbearing potential who is not currently pregnant.
10.3.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and is 
not a WOCBP (see definitions below in Section 10.3.3).
10.3.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following: 

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.

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For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. In addition:

A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT.

A female on HRT and whose menopausal status is in doubt will be required to use 
one of the nonestrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment.
10.3.4. Contraception Methods
As all female participants in this study are at least 65 years of age, contraceptive use is not
required for females.
Refer to Section 10.3.1 for male participants.

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10.4. Appendix 4: 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 “adaptors” 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.
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 participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected Hy’s law 
cases, 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, or 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, 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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10.5. Appendix 5: AEs, ADEs, SAEs, SADEs, USADEs, and Device Deficiencies 
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting in 
Medical Device Studies
Definitions of a Medical Device Deficiency
The definitions and procedures detailed in this appendix are in accordance with ISO 14155 
and the European MDR 2017/745 for clinical device research (if applicable).
Both the investigator and the sponsor will comply with all local reporting requirements for 
medical devices.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.3 for the list of sponsor medical 
devices).
10.5.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined in Appendix 2 (Section 10.2.1).

An ADE is defined as an AE related to the use of an investigational medical device. 
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
10.5.2. Definition of SAE, SADE, and USADE
SAE Definition

An SAE is defined in Appendix 2 (Section 10.2.2).
SADE Definition

An SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE.

Any device deficiency that might have led to an SAE if appropriate action had not been 
taken, intervention had not occurred, or circumstances had been less fortunate.
USADE Definition

A USADE is a serious adverse device effect that by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis management 
file.

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10.5.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance. Device deficiencies include 
malfunctions, use errors, and inadequate information supplied by the manufacturer.
10.5.4. Recording/Reporting and Follow-Up of Medical Device Deficiencies
Device Deficiency Recording

When a device deficiency occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant device deficiency information in the 
participant’s medical records, in accordance with the investigator’s normal clinical 
practice and will also capture the required information on the Medical Device 
Complaint form.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of following the reporting process described in the 
Medical Device Complaint form.

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.

If the investigator determines that the medical device deficiency may have injured the 
participant (ie, the medical device deficiency is associated with an AE or SAE), then the 
investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis will be documented 
in the participant’s medical record and recorded as the AE or SAE rather than the 
individual signs/symptoms. Requirements for recording and reporting an AE or SAE are 
provided in Appendix 2 (Section 10.2.3).

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a medical 
device where such action is necessary to prevent recurrence of a device deficiency. This 
includes any amendment to the device design to prevent recurrence.

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Assessment of Causality Occurring in Conjunction With a Medical Device Deficiency

If an AE or SAE has occurred in conjunction with a medical device deficiency, the 
investigator must assess the relationship between each occurrence of the AE or SAE and 
the medical device deficiency. The investigator will use clinical judgment to determine 
the relationship.

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.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each device deficiency, the investigator must document in the medical notes that 
he/she has reviewed the device deficiency and has provided an assessment of causality.

There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-Up of Medical Device Deficiency

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the device deficiency as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare providers.

New or updated information regarding the nature of the device deficiency will be 
recorded in the originally completed Medical Device Complaint form.

New or updated information regarding any SAE that was potentially associated with the 
medical device deficiency will be submitted to Pfizer Safety on the Vaccine SAE 
Reporting Form within 24 hours of receipt of the information, according to the 
requirements provided in Appendix 2, Section 10.2.

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10.5.5. Reporting of SAEs
Reporting of an SAE to Pfizer Safety must be performed according to the processes 
described in Appendix 2 (Section 10.2.4).
10.5.6. Reporting of SADEs
SADE Reporting to Pfizer Safety 
Note: There are additional reporting obligations for medical device deficiencies that are 
potentially related to SAEs (ie, a SADE) that must fulfill the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety information relating 
to medical devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the sponsor 
within 24 hours after the investigator determines that the event meets the definition of a 
device deficiency.

The sponsor shall review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These shall be reported to the regulatory 
authorities and IRBs/ECs as required by national regulations.

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10.6. Appendix 6: Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic and will become effective for other public emergencies only upon 
written notification from Pfizer.
Use of these alternative study measures is expected to cease upon the return of business as 
usual (including the lifting of any quarantines and travel bans/advisories).
10.6.1. Telehealth Visits
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the schedule of 
activities or unscheduled visits. Telehealth visits may be used to continue to assess 
participant safety and collect data points. Telehealth includes the exchange of healthcare 
information and services via telecommunication technologies (eg, audio, video, 
videoconferencing software) remotely, allowing the participant and the investigator to 
communicate on aspects of clinical care, including medical advice, reminders, education, and 
safety monitoring. The following assessments must be performed during a telehealth visit:

Review and record any AEs and SAEs since the last contact. Refer to Section 8.3.

Obtain details of any nonstudy vaccinations and concomitant medications and treatments 
as described in Section 6.10.

Confirm that the participant is adhering to the contraception method(s) required in the 
protocol.
Study participants must be reminded to promptly notify site staff about any change in their 
health status.

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10.7. Appendix 7: 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 infection 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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10.8. Appendix 8: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
ADE
adverse device effect
AE
adverse event
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
AST
aspartate aminotransferase
CFR
Code of Federal Regulations
CHF
congestive heart failure
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CONSORT
Consolidated Standards of Reporting Trials
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram
eCRF
electronic case report form
EDB
exposure during breastfeeding
e-diary
electronic diary
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FIH
first-in-human

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Abbreviation
Term
FI-RSV
formalin-inactivated respiratory syncytial virus vaccine
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMC
geometric mean concentration
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HAI
hemagglutination inhibition
HBe
hepatitis B e
HBeAg
hepatitis B e antigen
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IM
intramuscular
IND
investigational new drug application
INR
international normalized ratio
IPM
investigational product manual
IPAL
Investigational Product Accountability Log
IRB
institutional review board
IRT
interactive response technology
ISO
International Organization for Standardization
IV
intravenous
LFT
liver function test
LRTI
lower respiratory tract illness
LRTI-RSV
RSV-associated lower respiratory tract illness
MCAR
missing completely at random
MDR
medical device regulation
CCI

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Abbreviation
Term
MedDRA
Medical Dictionary for Regulatory Activities
mITT
modified intent-to-treat
N/A
not applicable
NT
neutralizing titer
PFS
prefilled syringe
PPE
personal protective equipment
PT
prothrombin time
QTL
quality tolerance limit
RCDC
reverse cumulative distribution curve
RNA
ribonucleic acid
RSV
respiratory syncytial virus
RSV A
respiratory syncytial virus subgroup A
RSV B
respiratory syncytial virus subgroup B
RSVpreF
respiratory syncytial virus stabilized prefusion F subunit vaccine
RT-PCR
reverse transcription–polymerase chain reaction
SADE
serious adverse device effect
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2 
SD
standard deviation
SIIV
seasonal inactivated influenza vaccine
SoA
schedule of activities
SOP
standard operating procedure 
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBD
to be determined
TBili
total bilirubin
Th2
T-helper type 2
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
WOCBP
woman/women of childbearing potential

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11. REFERENCES
1
Hall CB, Simőes EAF, Anderson LJ. Clinical and epidemiologic features of respiratory 
syncytial virus. Curr Top Microbiol Immunol. 2013;372:39-57. 
2
Chadha M, Hirve S, Bancej C, et al. Human respiratory syncytial virus and influenza 
seasonality patterns–early findings from the WHO global respiratory syncytial virus 
surveillance. Influenza Other Respir Viruses. 2020;14(6):638-46.
3
Baker RE, Park SW, Yang W, et al. The impact of COVID-19 nonpharmaceutical 
interventions on the future dynamics of endemic infections. Proc Nat Acad Sci USA.
2020;117(48):30547-53. 
4
Murata Y, Falsey AR. Respiratory syncytial virus infection in adults. Antivir Ther.
2007;12(4 Pt B):659-70.
5
Falsey AR, Hennessey PA, Formica MA, et al. Respiratory syncytial virus infection in 
elderly and high-risk adults. N Engl J Med. 2005;352(17):1749-59.
6
Ackerson B, Tseng HF, Sy LS, et al. Severe morbidity and mortality associated with 
respiratory syncytial virus versus influenza infection in hospitalized older adults. 
Clin Infect Dis. 2019;69(2):197-203.
7
Sundaram ME, Meece JK, Sifakis F, et al. Medically attended respiratory syncytial virus 
infections in adults aged ≥50 years: clinical characteristics and outcomes. Clin Infect 
Dis. 2014;58(3):342-9.
8
Belongia EA, King JP, Kieke BA, et al. Clinical features, severity, and incidence 
of RSV illness during 12 consecutive seasons in a community cohort of adults 
≥60 years old. Open Forum Infect Dis. 2018;5(12):ofy316.
9
Wyffels V, Kariburyo F, Gavart S, et al. A real-world analysis of patient characteristics 
and predictors of hospitalization among US Medicare beneficiaries with respiratory 
syncytial virus infection. Adv Ther. 2020;37(3):1203-17.
10
Domachowske JB, Anderson EJ, Goldstein M. The future of respiratory syncytial virus 
disease prevention and treatment. Infect Dis Ther. 2021;10(Suppl 1):S47-S60.
11
Centers for Disease Control and Prevention. Table 1. Influenza vaccines – United States, 
2020-21 influenza season. Available from: 
https://www.cdc.gov/flu/professionals/acip/2020-2021/acip-table.htm. Accessed: 
25 Aug 2021.

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National Centre for Immunisation Research and Surveillance. ATAGI recommendation 
for influenza vaccine in adults aged ≥65 years. Available from: 
https://www.ncirs.org.au/sites/default/files/2020-
12/Adjuvanted%20influenza%20vaccine%20vs%20standard%20dose%20influenza%20
vaccine%20GRADE%20recommendation_final.pdf. Accessed: 25 Aug 2021.
13
US Food and Drug Administration. Guidance for industry: toxicity grading scale for 
healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. 
Rockville, MD: Center for Biologics Evaluation and Research; Sep 2007.
14
Fluad Quad [prescribing information]. Parkville, VIC, Aus: Seqirus Pty Ltd; 2020. 
Available from:
https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-
2020-PI-02419-1&d=20210816172310101. Accessed: 25 Aug 2021
15
Agresti A. Introduction: distributions and inference for categorical data. Chapter 1. 
In: Agresti A, ed. Categorical data analysis. 2nd ed. Hoboken, NJ: John Wiley & Sons; 
2002:1-35.
16
Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985;4(2):
213-26.

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