A PHASE 1/2, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND,DOSE-FINDING, FIRST-IN-HUMAN STUDY TO DESCRIBE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF AN ADJUVANTED RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINE IN HEALTHY OLDER ADULTS
Phase: PHASE2
Conditions: Respiratory Tract Infection
Sponsor: Pfizer

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A PHASE 1/2, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, 
DOSE-FINDING, FIRST-IN-HUMAN STUDY TO DESCRIBE THE SAFETY, 
TOLERABILITY, AND IMMUNOGENICITY OF AN ADJUVANTED 
RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINE IN HEALTHY OLDER 
ADULTS
Investigational Product Number:
PF-06928316
Investigational Product Name:
Respiratory Syncytial Virus (RSV) Vaccine 
United States (US) Investigational New Drug
(IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
Not Applicable (N/A)
Protocol Number:
C3671002
Phase:
1/2
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
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Document History
Document
Version Date
Summary of Changes and Rationale
Protocol Amendment 3
22 August 2019
Document History: Added Summary of 
Changes for Amendment 3. Removed 
hyperlinks from Amendment 2 due to 
changes in formatting.
Protocol Summary: Added clarification 
text included in various sections of the 
main body of the protocol to match the 
revisions made to the protocol. 
Schedule of Activities: 
Table 1: Added a reference to Stage 1; 
changed the Visit 5 window; modified the 
blood volume collection for Visit 5; added 
the peripheral blood mononuclear cell 
(PBMC) abbreviation; amended the table 
footer. Table 2: Added a Schedule of 
Activities for the Primary Study Cohort -
Stage 2. Table 3: Added a schedule of 
activities for the RSV Vaccine Month-0, 
Month-2 Cohort.
Introduction: Added the rational for 
Amendment 3.
Study Objectives And Endpoints: Added 
text to clarify that the existing objectives 
and endpoints applied to the Primary 
Study Cohort - Stage 1/ vaccination 1. 
Added objectives and endpoints for the 
Primary Study Cohort - Stage 2 and the 
RSV Vaccine Month-0, Month-2 Cohort.
Study Design: Modified the text to 
introduce a new design of 3 cohorts: the 
Primary Study Cohort - Stage 1 and Stage 
2 and RSV Vaccine Month-0, Month-2 
Cohort.
Section 3.1: Updated the text to reflect the 
subject numbers based on the new design
and updated Table 4 based on the new 
subject numbers. Modified the table 

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Version Date
Summary of Changes and Rationale
footer.
Section 4: Added inclusion criterion 5. 
Modified exclusion criteria 4 and 5 to 
reflect the new design. Added exclusion 
criterion 14 so that elderly subjects are not 
compromised due to frequent blood 
draws. 
Section 5.1.2: Modified blinding text in 
line with the new design.
Section 5.4.1.1 and Table 5: Replaced 
“TBD” with the RSV vaccine dose.
Section 5.5: Modified the vaccine 
administration text to describe the timing 
of vaccinations by cohort. Table 6: 
Added administration information by 
cohort.
Section 5.8.2: Added a statement 
regarding the exclusionary period for the 
influenza vaccine for the Stage 2 cohort.
Section 5.8.3: Added applicability text for 
the administration of the influenza 
vaccine. Added a statement on the timing 
of the administration of the influenza 
vaccine for the RSV Month-0, Month-2 
Cohort.
Section 6: Added text to note that 
Section 6.1 applies to the Primary Study 
Cohort - Stage 1. Added text to 
emphasize that blood samples for cellular 
assays apply to consenting PBMC 
subjects at PBMC collection sites only. 
Section 6.2: Added a detailed visit 
schedule for the Primary Study Cohort -
Stage 2.
Section 6.3: Added a detailed visit 
schedule for the RSV Vaccine Month-0, 

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Month-2 Cohort.
Section 7.2: Modified the immunogenicity 
blood sample collection to reflect 
sampling by study cohort.
Section 7.3: Moved the text into a logical 
order based on the new design. Made 
slight modifications to text based on the 
new design.
Section 8.1.4: Clarified the text to 
emphasize the adverse event (AE)
collection periods based on the modified 
vaccination schedules.
Section 9: Modified the sample size 
determination by study cohort. Modified 
the probability table based on the new 
subject numbers per cohort.
Section 9.2: Modified study populations 
to reflect the new design.
Section 9.4: Modified text to show that 3 
interim analyses will be performed. Text 
includes timing relative to vaccination and 
data to be analyzed.
Section 9.5: Removed redundant text 
regarding the timing of the data 
monitoring committee (DMC) review as 
details are addressed in the DMC charter.
Throughout: Made minor editorial 
revisions as appropriate.

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Version Date
Summary of Changes and Rationale
Protocol Amendment 2
09 October 2018
Protocol Summary: Added clarification 
text included in various sections of the 
main body of the protocol to streamline 
the revisions made to the protocol.
Schedule of Activities: Deleted the 
sentinel-cohort table, the expanded cohort 
text within the table title, and the 2-month 
follow-up visit column; clarified the study 
assessments at scheduled visits for all 
subjects; added a subset of subjects at 
designated sites only, having whole blood 
samples collected at Visits 1, 2 (1-week 
and 1-month follow-up visits), and 4; 
added a Visit 2 (1-week follow-up visit) 
for the subset of subjects only.  Changes 
made in line with revisions to the study 
design and assessment visits.
Section 1.2 and Section 2: Added 
preliminary safety information from the 
C3671001 first-in-human study; added 
clarification regarding the rationale for 
this amendment and the revised study 
objectives and endpoints.
Section 3 and Section 5: Added 
clarification text to describe the changes 
to the study design, investigational 
product, and administration requirements 
for the study.
Section 4: Revised the inclusion and 
exclusion criteria text in line with study 
design changes and reorganized the 
criteria to address inconsistencies.
Section 6.1 through Section 6.10: Deleted 
assessment visits, including text specific 
to the sentinel cohort. Deleted text 
specific to the expanded cohort, but 
revised text to address the changes to the 
schedule of assessments and associated 
procedures. Revisions made in line with 
the revised study objectives and 

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endpoints.
Section 7.1, Section 7.2, and Section 
7.2.2: Added clarification text pertaining 
to the whole blood sampling procedures 
for the subset of subjects. New study 
assessment.
Section 7.1.1 through Section 7.1.3: 
Deleted text for laboratory assessments 
previously associated with the sentinel 
cohort, as this is no longer applicable to 
the study.
Section 7.3: Added safety text pertaining 
to the slow subject recruitment strategy 
during the first week of enrollment in the 
study, to maintain safety oversight.
Section 7.4: Revised stopping rule text for 
the current amendment. Revisions made 
in line with the changes to the study 
design and investigational product.
Section 8.1.4: Clarified the reporting 
requirements for adverse events and 
serious adverse events in the study.
Section 8.4.2: Clarified the reporting 
procedures for adverse events of specific 
interest.
Section 8.5: Clarified the medical device 
reporting requirements for the study.
Section 9: Added text to clarify the 
statistical analysis procedures in line with 
the current revisions.
Section 9.5: Deleted text regarding the 
IRC review process and dose escalation, 
as this is no longer applicable, as the 
sentinel cohort is no longer applicable to 
the study.
Appendix 2: Deleted the country-specific 

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criteria for South Africa only.
Throughout:  Several changes were made 
to this protocol amendment to incorporate 
the subset of subjects that will be 
providing whole blood samples for the 
exploratory objectives as part of the new 
study assessment.
Throughout: Made minor editorial 
revisions as appropriate.
Protocol Amendment 1
18 June 2018
Schedule of Activities (footnote b) and 
Section 3, Section 6.2, and Section 7.3: 
Added text to describe 4-hour 
observation of the first 4 subjects in the 
study age group of interest, vaccinated at 
the first site only, as requested by the 
central institutional review board (IRB).
Section 3: Revised text to clarify the 
randomization process in the sentinel and 
expanded cohorts.
Section 4.2: Expanded the exclusion 
criterion “History of severe adverse 
reaction associated with a vaccine and/or 
severe allergic reaction (eg, anaphylaxis) 
to any component of the investigational 
product(s)” to include “or history of 
severe allergic reaction (eg, anaphylaxis) 
to any substance,” for safety reasons.
Section 4.2, Section 5.8.2, and 
Section 5.8.3: Added inhaled/nebulized 
and topical epidural corticosteroids to the 
list of permitted corticosteroids, to 
address inconsistency with Section 4.3.
Section 5.1.2: Clarified that the personnel 
not directly involved in the study will 
review safety data (ie, rather than 
unblinded), according to an internal 
review committee (IRC) charter.
Section 5.4: Amended section title from 

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“Vaccine Supplies” to “Investigational 
Product Supplies.” 
Section 6.1 and Section 6.10: Added text 
to address the exception granted to 
Vaccines by the Global Standards Board 
to collect the subjectsÿ full date of birth.
Section 7.4.1: Clarified that meeting a 
stopping rule will halt randomization and 
not enrollment.
Section 9.5: Clarified that review by the 
IRC will determine if randomization in 
the next higher dose level should begin.
Appendix 2: Added the appendix to 
provide country-specific criteria for South 
Africa only.
Throughout: Made minor editorial 
revisions as appropriate.
Original protocol
05 December 2017
Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the
request of country health authorities and institutional review boards (IRBs)/ethics committees
(ECs), as well as information provided in any protocol administrative change letter(s).

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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................13
APPENDICES .........................................................................................................................14
PROTOCOL SUMMARY.......................................................................................................15
SCHEDULE OF ACTIVITIES................................................................................................22
1. INTRODUCTION ...............................................................................................................28
1.1. Indication.................................................................................................................28
1.2. Background and Rationale ......................................................................................28
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................32
3. STUDY DESIGN.................................................................................................................34
3.1. Number of Subjects.................................................................................................35
3.2. Duration of Subject Participation............................................................................37
3.3. Duration of Study....................................................................................................37
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................37
4.1. Inclusion Criteria.....................................................................................................37
4.2. Exclusion Criteria....................................................................................................38
4.3. Criteria for Temporarily Delaying Vaccine Administration...................................39
4.4. Lifestyle Requirements ...........................................................................................40
4.4.1. Contraception..............................................................................................40
4.5. Sponsor’s Qualified Medical Personnel..................................................................41
5. INVESTIGATIONAL PRODUCTS ...................................................................................41
5.1. Allocation to Investigational Product......................................................................41
5.1.1. Blinding of Study Site Personnel................................................................42
5.1.2. Blinding of the Sponsor..............................................................................42
5.2. Breaking the Blind ..................................................................................................42
5.3. Subject Compliance.................................................................................................43
5.4. Investigational Product Supplies.............................................................................43
5.4.1. Dosage Form(s) and Packaging..................................................................43
5.4.1.1. Respiratory Syncytial Virus Stabilized Prefusion F 
Subunit Vaccine.................................................................................43
5.4.1.2. Seasonal Inactivated Influenza Vaccine....................................44

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5.4.1.3. Placebo ......................................................................................44
5.4.2. Preparation and Dispensing........................................................................44
5.5. Administration.........................................................................................................44
5.6. Investigational Product Storage ..............................................................................45
5.7. Investigational Product Accountability...................................................................46
5.7.1. Destruction of Investigational Product Supplies ........................................47
5.8. Concomitant Treatment(s).......................................................................................47
5.8.1. Prohibited Nonstudy Vaccines Prior to the Study......................................47
5.8.2. Prohibited Nonstudy Vaccines and Medications During the Study ...........47
5.8.3. Permitted Nonstudy Vaccines and Medications During the Study ............47
5.8.4. Recording Nonstudy Vaccinations and Concomitant Medications............48
6. STUDY PROCEDURES .....................................................................................................48
6.1. Primary Study Cohort - Stage 1 ..............................................................................48
6.1.1. Primary Study Cohort - Stage 1, Visit 1: Vaccination (Day 1) ..................48
6.1.2. Primary Study Cohort - Stage 1, Visit 2: 1-Week Follow-up Visit (6-
8 Days After Visit 1) (applicable to consenting PBMC subjects at 
PBMC collection sites only).............................................................................50
6.1.3. Primary Study Cohort - Stage 1, Visit 2: 1-Month Follow-up Visit 
(28-35 Days After Visit 1) (applicable to all subjects) ...................................51
6.1.4. Primary Study Cohort - Stage 1, Visit 3: 3-Month Follow-up Visit 
(84-105 Days After Visit 1).............................................................................52
6.1.5. Primary Study Cohort - Stage 1, Visit 4: 6-Month Follow-up Visit 
(168-210 Days After Visit 1)...........................................................................52
6.1.6. Primary Study Cohort - Stage 1, Visit 5: 12-Month Follow-up Visit 
(300-400 Days After Visit 1)...........................................................................52
6.2. Primary Study Cohort - Stage 2 ..............................................................................53
6.2.1. Primary Study Cohort - Stage 2, Visit 5: 12-Month Follow-up Visit 
(300-400 Days After Visit 1)...........................................................................53
6.2.2. Primary Study Cohort - Stage 2, Visit 6A: 1-Week Revaccination 
Follow-up Visit (6 to 8 Days After Visit 5) (applies to subjects 
consenting to PBMC collection at PBMC collection sites only) .....................55
6.2.3. Primary Study Cohort - Stage 2, Visit 6: 1-Month Revaccination 
Follow-up Visit (28-35 Days After Visit 5) (applies to all subjects) ..............55
6.2.4. Primary Study Cohort - Stage 2, Visit 7: 3-Month Revaccination 
Follow-up Visit (84 to 105 Days After Visit 5) (applies to all subjects) ........56

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6.2.5. Primary Study Cohort - Stage 2, Visit 8: 6-Month Revaccination 
Follow-up Visit (168 to 210 Days After Visit 5) (applies to all subjects) ......56
6.2.6. Primary Study Cohort - Stage 2, Visit 9: 12-Month Revaccination 
Follow-up Visit (350 to 378 Days After Visit 5) (applies to all subjects) ......57
6.3. RSV Vaccine Month-0, Month-2 Cohort................................................................57
6.3.1. RSV Vaccine Month-0, Month-2 Cohort, Visit 1: Vaccination 1 
(Day 1) .............................................................................................................57
6.3.2. RSV Vaccine Month-0, Month-2 Cohort, Visit 2A: 1-Week Follow-
up Visit (6 to 8 Days After Visit 1) (applies to subjects consenting to 
PBMC collection at PBMC collection sites only)............................................59
6.3.3. RSV Vaccine Month-0, Month-2 Cohort, Visit 2: 1-Month Follow-
up Visit (28 to 35 Days After Visit 1) (applies to all subjects).......................60
6.3.4. RSV Vaccine Month-0, Month-2 Cohort, Visit 3: Vaccination 2 Visit 
(54 to 66 Days After Visit 1) (applies to all subjects).....................................60
6.3.5. RSV Vaccine Month-0, Month-2 Cohort, Visit 4Aa: 1-Week Post-
Vaccination 2 Follow-up Visit (6 to 8 Days After Visit 3) (applies to 
subjects consenting to PBMC collection at PBMC collection sites only) .......62
6.3.6. RSV Vaccine Month-0, Month-2 Cohort, Visit 4: 1-Month Post-
Vaccination 2 Follow-up Visit (28 to 35 Days After Visit 3) (applies to 
all subjects)......................................................................................................62
6.3.7. RSV Vaccine Month-0, Month-2 Cohort, Visit 5: 6-Month Follow-
up Visit (168 to 210 Days After Visit 3) (applies to all subjects)...................63
6.3.8. RSV Vaccine Month-0, Month-2 Cohort, Visit 6: 12-Month Follow-
up Visit (350 to 378 Days After Visit 3) (applies to all subjects)...................63
6.4. Unscheduled Reactogenicity Visits Following Vaccination...................................64
6.5. Subject Withdrawal.................................................................................................66
7. ASSESSMENTS..................................................................................................................66
7.1. Biological Samples..................................................................................................67
7.2. Immunogenicity ......................................................................................................67
7.2.1. RSV and Influenza Vaccine Antibody Testing ..........................................68
7.2.2. Exploratory Assays, Immunogenicity Assessments, and Assay 
Development....................................................................................................68
7.3. Safety Parameters....................................................................................................69
7.3.1. Subject Electronic Diary.............................................................................69
7.3.2. Grading Scales............................................................................................70
7.3.3. Local Reactions ..........................................................................................70

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7.3.4. Systemic Events..........................................................................................71
7.3.5. Fever ...........................................................................................................72
7.3.6. Use of Antipyretic/Pain Medication...........................................................73
7.4. Stopping Rules ........................................................................................................73
7.4.1. Randomization and Vaccination After a Stopping Rule Is Met .................74
8. ADVERSE EVENT REPORTING......................................................................................74
8.1. Requirements...........................................................................................................74
8.1.1. Additional Details on Recording Adverse Events on the CRF...................76
8.1.2. Eliciting Adverse Event Information..........................................................76
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Subject Withdrawal section)............................................................................76
8.1.4. Time Period for Collecting AE/SAE Information......................................76
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................77
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF...................77
8.1.5. Causality Assessment .................................................................................77
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................78
8.2. Definitions...............................................................................................................78
8.2.1. Adverse Events...........................................................................................78
8.2.2. Abnormal Test Findings .............................................................................79
8.2.3. Serious Adverse Events ..............................................................................79
8.2.4. Hospitalization............................................................................................80
8.3. Severity Assessment................................................................................................81
8.4. Special Situations ....................................................................................................82
8.4.1. Protocol-Specified Serious Adverse Events...............................................82
8.4.2. Adverse Events of Specific Interest............................................................82
8.4.3. Potential Cases of Drug-Induced Liver Injury............................................84
8.4.4. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................86
8.4.4.1. Exposure During Pregnancy......................................................86
8.4.4.2. Exposure During Breastfeeding ................................................87
8.4.4.3. Occupational Exposure .............................................................87
8.4.5. Medication Errors .......................................................................................88
8.4.5.1. Medication Errors......................................................................88

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8.5. Medical Device Complaint Reporting Requirements .............................................89
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................89
9.1. Sample Size Determination.....................................................................................89
9.2. Immunogenicity Analysis .......................................................................................90
9.2.1. Immunogenicity Analysis Populations.......................................................90
9.2.1.1. Primary Study Cohort - Stage 1 ................................................90
9.2.1.2. Primary Study Cohort - Stage 2 ................................................90
9.2.1.3. RSV Vaccine Month-0, Month-2 Cohort..................................91
9.2.2. Analysis of Immunogenicity Endpoints .....................................................91
9.3. Safety Analysis........................................................................................................92
9.4. Analysis Timing ......................................................................................................93
9.5. Data Monitoring Committee(s) ...............................................................................93
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................94
11. DATA HANDLING AND RECORD KEEPING .............................................................95
11.1. Case Report Forms/Electronic Data Record .........................................................95
11.2. Record Retention...................................................................................................95
12. ETHICS..............................................................................................................................96
12.1. Institutional Review Board/Ethics Committee......................................................96
12.2. Ethical Conduct of the Study ................................................................................96
12.3. Subject Information and Consent..........................................................................96
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................97
13. DEFINITION OF END OF TRIAL...................................................................................97
13.1. End of Trial in All Participating Countries ...........................................................97
14. SPONSOR DISCONTINUATION CRITERIA ................................................................97
15. PUBLICATION OF STUDY RESULTS..........................................................................97
15.1. Communication of Results by Pfizer ....................................................................97
15.2. Publications by Investigators ................................................................................98
16. REFERENCES ................................................................................................................100
LIST OF TABLES
Table 1.
Schedule of Activities: Primary Study Cohort - Stage 1 ..........................22

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Table 2.
Schedule of Activities: Primary Study Cohort - Stage 2..........................24
Table 3.
Schedule of Activities: RSV Vaccine Month-0, Month-2 Cohort............26
Table 4.
Randomization of Subjects by Dose and Formulation .............................36
 
Table 6.
Location of Intramuscular Injection .........................................................45
Table 7.
Grading Scale for Local Reactions...........................................................71
Table 8.
Grading Scale for Systemic Events ..........................................................71
Table 9.
Ranges for Fever.......................................................................................73
Table 10.
Autoimmune Diseases/Disorders..............................................................82
Table 11.
Probability of Observing at Least 1 AE by Assumed True Event 
Rates With Different Sample Sizes ..........................................................90
APPENDICES
Appendix 1. Abbreviations....................................................................................................101
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PROTOCOL SUMMARY
Indication
The respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSV vaccine) 
is being developed for the following indication:
•
Prevention of RSV-associated moderate to severe lower respiratory tract disease in adults 
60 years of age and older via active immunization.
Primary Objective:
Primary Endpoints:
Primary Study Cohort - Stage 1
To describe the safety and tolerability of an 
adjuvanted RSV vaccine given concomitantly 
with seasonal inactivated influenza vaccine 
(SIIV).
Primary Study Cohort - Stage 1
•
Local reactions within 14 days after 
Vaccination 1.
•
Systemic events within 14 days after 
Vaccination 1.
•
Adverse events (AEs) within 1 month 
after Vaccination 1.
•
Medically attended AEs and serious 
adverse events (SAEs) through 12 
months after Vaccination 1 (from Visit 1 
through Visit 5).
Study Design
This is a Phase 1/2, multicenter, randomized, placebo-controlled, observer-blind, dose-and 
formulation-finding study to describe the safety, tolerability, and immunogenicity of up to 
7 different RSV vaccine candidates with bivalent formulations (RSV A and RSV B) at 3 dose 
levels of 60 μg of the prefusion RSV F antigens 
 
 120 μg 
(
 
 
 and 240 μg 
 
 
formulated with aluminum 
hydroxide (Al[OH]3) or CpG/Al(OH)3, or a 240 μg RSV vaccine 
 
alone, when administered concomitantly with SIIV, or without SIIV in a Month-0, Month-2 
schedule. 
The dose for the RSV vaccine alone was selected based on 1-month postvaccination 
immunogenicity data from the sentinel-cohort subjects in Study C3671001 (A Phase 1/2, 
Placebo-Controlled, Randomized, Observer-Blind, Dose-Finding, First-in-Human Study to 
Describe the Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus 
(RSV) Vaccine in Healthy Adults; ClinicalTrials.gov identifier: NCT03529773).
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The C3671002 study was initiated under protocol Amendment 2 during the southern 
hemisphere influenza season; however, a delay in SIIV availability prevented completion of 
enrollment of the original cohort.  Consequently, only 250 subjects of the planned 312 
subjects were enrolled. In Amendment 3, this cohort will be referred to as the Primary Study 
Cohort - Stage 1.
Enrollment in the Primary Study Cohort - Stage 1 commenced in April 2019 and completed 
enrollment in June 2019. 
Approximately 250 subjects 65 to 85 years of age received 2 intramuscular injections at Visit 
1 to assess the concomitant administration of SIIV when given to subjects receiving one of 
the 3 RSV vaccine dose-level candidates formulated with Al(OH)3 or CpG/Al(OH)3 or the 
RSV vaccine–alone dose (see Section 6.1 for further details).  
The first 4 subjects vaccinated in the study were observed by blinded site staff for any acute 
reactions for at least 4 hours after vaccination.  Vaccination of the remaining subjects 
commenced no sooner than 48 hours after the fourth subject received his or her vaccination.  
Vaccination of subjects was limited to a maximum of 6 subjects per day during the first week 
of enrollment (up to 30 vaccinated subjects in total). Follow-up will continue through 
Month 12.
Protocol Amendment 3 will address 2 broad goals:
1. Evaluate a 2-dose regimen administered 2 months apart to determine whether a short 
dosing interval elicits an enhanced immune response. 
Due to the deficit in the originally planned subject enrollment, approximately 62 subjects 
aged 65-85 years will be randomized 1:1 to receive a dose of 240 g RSV vaccine with 
CpG/Al(OH)3 or placebo followed by a second dose 2 months later. Safety, tolerability, 
and immunogenicity will be evaluated. This cohort will be known as the RSV Vaccine 
Month-0, Month-2 Cohort. The subjects will be enrolled before the influenza season. 
There will be no concomitant SIIV administration. 
2. Evaluate safety and immunogenicity of a second dose of RSV vaccine administered to 
the Primary Study Cohort - Stage 1 subjects, 12 months after the initial dose to determine 
whether the immune response supports annual vaccination.
The safety and immunogenicity data from C3671001 and Stage 1 of C3671002 will guide 
the decision on whether a second dose of the RSV vaccine will be evaluated in Stage 2. If 
Stage 2 proceeds, this cohort will be known as the Primary Study Cohort - Stage 2. If 
there are no substantial differences in immune responses between the CpG/Al(OH)3 and 
Al(OH)3 formulations, then development of the CpG/Al(OH)3 formulation may cease, and 
Stage 2 will not proceed.

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If the data support implementation of Stage 2, invited, consenting subjects will be 
revaccinated with the same dose and formulation of the RSV vaccine or placebo received 
at Visit 1, concomitantly with SIIV. The safety, tolerability, and immunogenicity of the 
second dose will be evaluated through 12 months after revaccination. 

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Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document (ICD) indicating 
that the subject has been informed of all pertinent aspects of the study.
2. Healthy adults who are determined by medical history, physical examination, and clinical 
judgment of the investigator to be eligible for inclusion in the study.
Note: Healthy subjects with preexisting stable disease, defined as disease not requiring 
significant change in therapy or hospitalization for worsening disease within 6 weeks before 
enrollment, can be included.
3.
Willing and able to comply with scheduled visits, vaccination plan, laboratory tests, and 
other study procedures.
4.
Male and nonchildbearing-potential female adults 65 to 85 years of age at the time of 
enrollment (signing of the ICD).
Note: Female subjects of nonchildbearing potential must meet at least 1 of the following 
criteria:

Postmenopausal status, defined as follows: cessation of regular menses for at least 
12 consecutive months with no alternative pathological or physiological cause; status 
may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming 
the postmenopausal state;

Have undergone a documented hysterectomy and/or bilateral oophorectomy; 

Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are considered to be 
of childbearing potential.
5. Subjects must have received the primary vaccination (RSV vaccine or placebo) at Visit 1 
and have signed and dated the ICD for participating in the revaccination stage (applies to 
Primary Study Cohort - Stage 2 subjects).

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Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or subjects 
who are Pfizer employees, including their family members, directly involved in the 
conduct of the study.
2. Participation in other studies involving investigational product within 28 days prior to 
study entry and/or during study participation.
3. Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or 
hepatitis B virus (HBV).
4. Previous vaccination with any licensed or investigational RSV vaccine before enrollment 
into the study, or planned receipt throughout the study of nonstudy RSV vaccine.
5. Vaccination with any influenza vaccine within 6 months (182 days) before 
investigational product administration (applies to Primary Study Cohort - Stages 1 and 2).
6. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product(s), including 
natural rubber latex. In addition, a history of severe allergic reaction (eg, anaphylaxis) to 
any substance, including documented allergy to egg proteins (egg or egg products) or 
chicken proteins.
7. Subjects with known or suspected immunodeficiency, as determined by history and/or 
laboratory/physical examination.
8. Subjects receiving treatment with immunosuppressive therapy, including cytotoxic agents 
or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt 
throughout the study.  If systemic corticosteroids have been administered short term 
(<14 days) for treatment of an acute illness, subjects should not be enrolled into the study 
until corticosteroid therapy has been discontinued for at least 28 days before 
investigational product administration. Inhaled/nebulized, intra-articular, intrabursal, or 
topical (epidural, skin, or eyes) corticosteroids are permitted.
9. Subjects with a history of autoimmune disease or an active autoimmune disease requiring 
therapeutic intervention including but not limited to: systemic or cutaneous lupus 
erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, 
multiple sclerosis, Sjögren syndrome, idiopathic thrombocytopenic purpura, autoimmune 
glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), 
psoriasis, and insulin-dependent diabetes mellitus (type 1).

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10. Receipt of any blood/plasma products or immunoglobulin, from 60 days before 
investigational product administration or planned receipt throughout the study.
11. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
12. Female subjects of childbearing potential or who are pregnant or breastfeeding; fertile 
male subjects who are unwilling to use a highly effective method of contraception for at 
least 28 days after the last dose of investigational product.
13. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the subject inappropriate for entry into this study.
14. Planned donation of blood volumes of approximately 470 mL within 12 weeks after 
Vaccination 1 (applies to subjects having additional blood drawn for cellular assays).
Investigational Products
Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine
 
 
There are 3 different presentations of RSV drug product. The Al(OH)3- and 
CpG/Al(OH)3-containing formulations consist of 3 different dose levels of lyophilized RSV 
antigen (60 μg, 120 μg, and 240 μg). The RSV antigens without Al(OH)3 or CpG/Al(OH)3
will consist of a single dose level (240 μg).  The lyophilized cake is reconstituted with one of 
3 diluents: a sterile suspension of Al(OH)3 in water for injection, a sterile suspension of 
CpG/Al(OH)3, or sterile water for injection.
Seasonal Inactivated Influenza Vaccine
Commercially available high-dose (HD) trivalent SIIV (if available) or quadrivalent SIIV 
will be administered to the Primary Study Cohort - Stages 1 and 2. 
Investigational sites will be notified which commercially available SIIV will be provided 
prior to the start of enrollment.
Placebo
The placebo will be a sterile normal saline solution for injection (0.9% sodium chloride 
injection, in a 0.5-mL dose).
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Statistical Methods
The study sample sizes are not based on any formal statistical hypothesis testing. Statistical 
analysis will be descriptive in nature.
The safety analyses include local reactions, systemic events, AEs, medically attended AEs 
(MAEs), AEs of specific interest, and SAEs.  AEs will be categorized according to the 
Medical Dictionary for Regulatory Activities (MedDRA). The counts and percentages will 
be provided for AEs and e-diary events, with 2-sided 95% exact CIs as appropriate.
For immunogenicity endpoints, geometric mean titer (GMT) and geometric mean fold rise 
(GMFR) from baseline will be calculated by vaccine group and by cohort along with the 95% 
confidence intervals.  Relevant comparisons between vaccine groups and by cohorts will be 
based on the ratios of postvaccination GMTs, and the associated 2-sided 95% confidence 
intervals will also be constructed.
The percentages of subjects achieving seroprotection and seroconversion at 1 month after 
vaccination will be computed for each virus strain contained in SIIV separately.
Interim Analyses
Three interim analyses outlined in Section 9.4 are planned before the final analysis at the 
completion of the study. The results of these analyses will be used to select the most 
appropriate dose(s), formulation(s), and dosing schedule of the RSV vaccine for use in
further studies.

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SCHEDULE OF ACTIVITIES
The Schedule of Activities table provides an overview of the protocol visits and procedures.  Refer to the Study Procedures and 
Assessments sections of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. The investigator may schedule visits (unplanned visits) in addition to those listed on the Schedule of Activities table, in 
order to conduct evaluations or assessments required to protect the well-being of the subject.
Table 1 Schedule of Activities applies to those subjects participating in the Primary Study Cohort - Stage 1 (single dose administration 
of RSV vaccine/placebo given concomitantly with SIIV). Study procedures for this cohort are fully described in Section 6.1.
Table 1.
Schedule of Activities: Primary Study Cohort - Stage 1
Visit Number
1
2 a
2
3
4
5 b
Visit Description
Vaccination
1-Week Follow-
up Visit
1-Month 
Follow-up Visit
3-Month 
Follow-up Visit
6-Month 
Follow-up Visit
12-Month 
Follow-up Visit
Study Period
Month 0
Month 1
Month 3
Month 6
Month 12
Visit Window (Days)
Day 1
6 to 8 Days 
After Visit 1
28 to 35 Days 
After Visit 1
84 to 105 Days 
After Visit 1
168 to 210 Days 
After Visit 1
300 to 400 Days 
After Visit 1
Obtain informed consent
X
Assign subject number 
X
Obtain demography and medical history data
X
Assess tobacco usage
X
Document medications currently taken
X
Perform physical examination, including vital 
signs (weight, height, oral temperature, heart rate, 
and seated blood pressure)
X
Collect nonstudy vaccine information 
X
X
X
X
X
X
Confirm eligibility
X
Review temporary delay criteria
X
Confirm understanding of and compliance with 
protocol requirements for contraception 
(male subjects only)
X
X
X

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Table 1.
Schedule of Activities: Primary Study Cohort - Stage 1
Visit Number
1
2 a
2
3
4
5 b
Visit Description
Vaccination
1-Week Follow-
up Visit
1-Month 
Follow-up Visit
3-Month 
Follow-up Visit
6-Month 
Follow-up Visit
12-Month 
Follow-up Visit
Study Period
Month 0
Month 1
Month 3
Month 6
Month 12
Visit Window (Days)
Day 1
6 to 8 Days 
After Visit 1
28 to 35 Days 
After Visit 1
84 to 105 Days 
After Visit 1
168 to 210 Days 
After Visit 1
300 to 400 Days 
After Visit 1
Assign randomization number
X
Collect blood sample for antibody assessment
~50 mL
~50 mL
~50 mL
~50 mL
~50 mL
~25 mL
Collect blood sample for cellular assay c
~100 mL
~50 mL
~50 mL
~50 mL
Administer investigational product and SIIV in 
opposite arms
X
Assess acute reactions for at least 30 minutes after 
investigational product administration
X
Provide subject with 14-day e-diary, thermometer, 
and measuring device
X
Review e-diary data (daily review is optimal 
during the active diary period)
-------------------X---------------------
Review and/or collect e-diary
X
Collect AEs, medically attended AEs, AEs of 
specific interest, and SAEs as appropriate
X
X
X
X
X
X
Abbreviations: e-diary = electronic diary; SIIV = seasonal inactivated influenza vaccine; PBMC = peripheral blood mononuclear cell.
a.
This visit is only applicable to subjects consenting to PBMC collection at designated PBMC sites.
b.
This Visit 5 schedule applies only to subjects who are not invited or do not consent to revaccination at Month 12.
c.
This blood collection is only applicable to subjects consenting to PBMC collection at designated PBMC sites.

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Table 2 Primary Study Cohort - Stage 2 Schedule of Activities is applicable to Stage 1 subjects who are invited and consent to 
revaccination at Month 12. Study procedures for this cohort are fully described in Section 6.2.
Table 2.
Schedule of Activities: Primary Study Cohort - Stage 2
Visit Number
5 a
6A b
6
7
8
9
Visit Description
Vaccination 2
1-Week 
Revaccination 
Follow-up 
Visit
1-Month 
Revaccination 
Follow-up Visit
3-Month 
Revaccination 
Follow-up Visit
6-Month 
Revaccination 
Follow-up Visit
12-Month 
Revaccination 
Follow-up Visit
Study Period
Month 12
Month 13
Month 15
Month 18
Month 24
Visit Window (Days)
300 to 400 Days 
after Visit 1
6 to 8 Days 
After Visit 5
28 to 35 Days 
After Visit 5
84 to 105 Days 
After Visit 5
168 to 210 Days 
After Visit 5
350 to 378 Days 
After Visit 5
Confirm/obtain informed consent for Stage 2 c
X
Perform physical examination, vital signs (weight, 
oral temperature, heart rate, and seated blood 
pressure)
X
Review inclusion/exclusion criteria
X
Record nonstudy vaccine information
X
X
X
X
X
X
Review temporary delay criteria
X
Confirm understanding and compliance with 
protocol requirements for contraception 
(male subjects)
X
X
X
Obtain IP container number
X
Collect blood sample for antibody assessment
~25 mL
~25 mL
~25 mL
~25 mL
~25 mL
Collect blood sample for cellular assay d
~100 mL
~50 mL
~50 mL
~50 mL
Administer investigational product in left deltoid 
muscle and SIIV in right deltoid muscle 
X
Assess acute reactions for at least 30 minutes after 
investigational product administration
X
Provide subject with 14-day e-diary, thermometer, 
and measuring device
X
Review e-diary data (daily review is optimal 
-------------------X---------------------

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Table 2.
Schedule of Activities: Primary Study Cohort - Stage 2
Visit Number
5 a
6A b
6
7
8
9
Visit Description
Vaccination 2
1-Week 
Revaccination 
Follow-up 
Visit
1-Month 
Revaccination 
Follow-up Visit
3-Month 
Revaccination 
Follow-up Visit
6-Month 
Revaccination 
Follow-up Visit
12-Month 
Revaccination 
Follow-up Visit
Study Period
Month 12
Month 13
Month 15
Month 18
Month 24
Visit Window (Days)
300 to 400 Days 
after Visit 1
6 to 8 Days 
After Visit 5
28 to 35 Days 
After Visit 5
84 to 105 Days 
After Visit 5
168 to 210 Days 
After Visit 5
350 to 378 Days 
After Visit 5
during the active diary period)
14 days
Review and collect e-diary
X
Record AEs, medically attended AEs, AEs of 
specific interest, and SAEs as appropriate
X
X
X
X
X
X
Abbreviations: e-diary = electronic diary; SIIV = seasonal inactivated influenza vaccine; PBMC = peripheral blood mononuclear cell.
a.
This Visit 5 schedule applies to subjects invited and consenting to revaccination at Month 12.
b.
Visit 6A is only applicable to subjects consenting to PBMC collection at designated PBMC sites.
c.
Consent may be obtained prior to Visit 5.
d.
This blood collection is only applicable subjects consenting to PBMC collection at designated PBMC sites.

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Table 3 Schedule of Activities is applicable to subjects participating in the RSV Vaccine Month-0, Month-2 Cohort. Study procedures 
for this cohort are fully described in Section 6.3.
Table 3.
Schedule of Activities: RSV Vaccine Month-0, Month-2 Cohort
Visit Number
1
2A a
2
3
4A a
4
5
6
Visit Description
Vaccination
1
1-Week 
Post-
Vaccination
1 Follow-up 
Visit
1-Month 
Post-
Vaccination
1 Follow-up 
Visit
Vaccination 
2
1-Week 
Post-
Vaccination
2 Visit
1-Month
Post-
Vaccination
2 Visit
6-Month 
Post-
Vaccination
2
Visit
12-Month 
Post-
Vaccination
2
Visit
Study Period
Month 0
Month 1
Month 2
Month 3
Month 8
Month 14
Visit Window (Days)
Day 1
6 to 8 Days 
After Visit 1
28 to 35 
Days After 
Visit 1
54 to 66
Days After 
Visit 1
6 to 8 Days 
After
Visit 3
28 to 35 
Days After 
Visit 3
168 to 210 
Days After 
Visit 3
350 to 378 
Days After 
Visit 3
Obtain informed consent
X
Assign subject number
X
Obtain demography and medical history 
data
X
Assess tobacco usage
X
Document medications currently taken
X
Perform physical examination, including 
vital signs (weight, height, oral 
temperature, heart rate, and seated blood 
pressure)
X
Record nonstudy vaccine information
X
X
X
X
X
X
X
X
Confirm eligibility
X
Review temporary delay criteria
X
X
Confirm understanding of and compliance 
with protocol requirements for 
contraception (male subjects only)
X
X
X
X
X
X
Assign randomization number
X
Collect blood sample for antibody 
~25 mL
~25 mL
~25 mL
~25 mL
~25 mL
~25 mL

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Table 3.
Schedule of Activities: RSV Vaccine Month-0, Month-2 Cohort
Visit Number
1
2A a
2
3
4A a
4
5
6
Visit Description
Vaccination
1
1-Week 
Post-
Vaccination
1 Follow-up 
Visit
1-Month 
Post-
Vaccination
1 Follow-up 
Visit
Vaccination 
2
1-Week 
Post-
Vaccination
2 Visit
1-Month
Post-
Vaccination
2 Visit
6-Month 
Post-
Vaccination
2
Visit
12-Month 
Post-
Vaccination
2
Visit
Study Period
Month 0
Month 1
Month 2
Month 3
Month 8
Month 14
Visit Window (Days)
Day 1
6 to 8 Days 
After Visit 1
28 to 35 
Days After 
Visit 1
54 to 66
Days After 
Visit 1
6 to 8 Days 
After
Visit 3
28 to 35 
Days After 
Visit 3
168 to 210 
Days After 
Visit 3
350 to 378 
Days After 
Visit 3
assessment
Collect blood sample for cellular assay b
~100 mL
~50 mL
~50 mL
~50 mL
~50 mL
~50 mL
~50 mL
~50 mL
Administer investigational product in the 
LEFT deltoid muscle
X
X
Assess acute reactions for at least 30 
minutes after investigational product 
administration
X
X
Provide subject with 14-day e-diary, 
thermometer, and measuring device
X
X
Review e-diary data (daily review is 
optimal during the active diary period)
        -----------------X---------------
                       14 days
         ----------------X-------------
                  14 days
Review and collect e-diary
X
X
Record AEs, medically attended AEs, 
AEs of specific interest, and SAEs as 
appropriate
X
X
X
X
X
X
X
X
Abbreviations: e-diary = electronic diary; PBMC = peripheral blood mononuclear cell.
a.
Visit is only applicable to subjects consenting to PBMC collection at designated PBMC sites.
b.
This blood collection is only applicable subjects consenting to PBMC collection at designated PBMC sites.

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1. INTRODUCTION
1.1. Indication
The respiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine (RSV vaccine)
is being developed for the following indication:

Prevention of RSV-associated moderate to severe lower respiratory tract disease in adults 
60 years of age and older via active immunization.
1.2. Background and Rationale
Human respiratory syncytial virus (HRSV) is the type species of the genus Pneumovirus, 
subfamily Pneumovirinae, family Paramyxoviridae, order Mononegavirales. HRSV exists as 
2 antigenic subgroups, A and B, which exhibit genome-wide sequence divergence. RSV is a 
global pathogen, causing yearly wintertime epidemics in temperate climates, usually between 
late fall and early spring, lasting 3 to 4 months in a community.  In tropical climates, there is 
no distinct seasonality and outbreaks are more unpredictable, continuous, and generally 
associated with rainy seasons.1
Since its identification in 1956, RSV has consistently been noted as the single most important 
cause of lower respiratory tract infection (LRTI) in infants <1 year of age worldwide. RSV 
is most notably associated with signs and symptoms of increased airway resistance 
manifested as wheezing and, in the young child, diagnosed as bronchiolitis. The acute illness 
usually lasts about 5 to 10 days, but the cough may be prolonged for several weeks.1
Globally, the incidence of RSV-associated acute LRTI was estimated in 2015 to be 
approximately 33 million episodes in children younger than 5 years, which resulted in about 
3.2 million hospital admissions and about 59,600 hospital deaths. In children younger than 
6 months, it is estimated that globally approximately 1.4 million hospital admissions, and 
approximately 27,300 hospital deaths, were due to RSV-associated acute LRTI.2
RSV is increasingly recognized as an important cause of severe respiratory disease in adults 
60 years of age or older as well as individuals with underlying cardiopulmonary and 
immunocompromised conditions.1 The clinical presentation of RSV in older adults is not 
distinctive, and more severe illness is often diagnosed as exacerbation of comorbid 
conditions, such as chronic obstructive pulmonary disease (COPD) and congestive heart 
failure.1 It is estimated that between 11,000 and 17,000 adults die of RSV infection annually 
in the United States, with approximately 10-fold more admitted to hospital with respiratory 
symptoms.3  In a US study, it was estimated that the yearly rate of RSV hospitalization 
among persons 50 to 64 years old was 0.82/1000, and among persons 65 years of age it was 
2.5/1000.4
Currently, there is no vaccine to protect against RSV disease.  Treatment consists primarily 
of supportive care.  There is, however, a prophylactic humanized monoclonal antibody 
against the RSV fusion (F) glycoprotein, palivizumab (Synagis, AstraZeneca), with 
demonstrated safety and efficacy against severe RSV disease in young infants.5,6

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The antibody is costly, requires multiple monthly injections, and is recommended for use 
only in high-risk and premature infants.6 The protective effect of Synagis is definitive proof 
of concept that serum neutralizing antibody directed against the F protein can provide 
clinically meaningful protection against RSV lower respiratory tract disease in young infants.
Pfizer is developing a vaccine for the prevention of RSV-associated LRTI, in order to protect 
infants by maternal immunization during pregnancy, and adults 60 years of age and older via 
direct immunization.
The aim of RSV vaccination in adults 60 years of age and over is to boost the immune 
response sufficiently to protect against RSV disease before each RSV season.  After RSV 
natural infection, there is only a relatively short duration of immunity.1  Serum neutralizing 
antibody titers in RSV-infected patients who were hospitalized compared with 
nonhospitalized infected persons suggest that more severe RSV disease is associated with 
low serum neutralizing antibody.7 Additional immune mechanisms may also aid in 
protection, but the existing evidence supports an important role for serum neutralizing
antibody titers in reducing the risk of RSV disease in older adults.
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
Because immunosenescence8 could pose a barrier to effective immunization of the elderly 
against RSV, there is concern that despite findings in animals suggesting that Al(OH)3
improves the immune response to the vaccine, the addition of Al(OH)3 alone may not be 
sufficient to optimize responses in the elderly, who are at significant risk from RSV disease.
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In this study in older adults 65 to 85 years of age, a CpG with aluminum hydroxide 
(CpG/Al[OH]3)-adjuvanted formulation, given as a single dose or in a 2-dose regimen
administered 2 months apart, will be investigated to assess if the addition of CpG could 
further improve neutralizing antibody levels relative to formulations with or without Al(OH)3
at the same dose levels used in the FIH study. In this event, a CpG/Al(OH)3-adjuvanted 
formulation would be included in further development studies. CpG is a Toll-like receptor 9 
(TLR9) agonist that has been generally well tolerated in human clinical trials for infectious 
disease indications, such as hepatitis B, malaria, and influenza.9  A CpG-containing hepatitis 
B vaccine, Heplisav-B, was recently licensed in the United States.10  
 
 
  Additionally, it is anticipated that an RSV vaccine 
would optimally be given at the same time as a seasonal influenza vaccine, to facilitate its 
use in the older adult population. Therefore, this study will assess any potential impact on 
safety, tolerability, and immune responses to the seasonal inactivated influenza vaccine 
(SIIV) when the RSV vaccine and SIIV are given concomitantly; similar assessments of 
concomitant administration of influenza vaccine and RSV vaccine with or without Al(OH)3
are being conducted in the C3671001 study.
Data from the C3671001 study at 1 month after administration of the 3 dose levels of RSV 
vaccine (60 μg, 120 μg, and 240 μg), with or without Al(OH)3 in subjects aged 18 to 85 
years, have shown the vaccine is well tolerated and immunogenic, with a trend toward 
greater immunogenicity at the 240-μg dose level.
The C3671002 study was initiated under protocol Amendment 2 during the southern 
hemisphere influenza season; however, a delay in SIIV availability prevented the completion 
of enrollment of the original cohort. Consequently, only 250 subjects of the planned 312 
subjects were enrolled. In Amendment 3, this cohort will be referred to as the Primary Study 
Cohort - Stage 1.
Protocol Amendment 3 will address 2 broad goals:
1. Evaluate a 2-dose regimen administered 2 months apart to determine whether a short 
dosing interval elicits an enhanced immune response. 
Due to the deficit in the originally planned subject enrollment, approximately 62 subjects 
aged 65-85 years will be randomized 1:1 to receive a dose of 240 μg RSV vaccine with 
CpG/Al(OH)3 or placebo followed by a second dose 2 months later. Safety, tolerability, 
and immunogenicity will be evaluated. This cohort will be known as the RSV Vaccine 
Month-0, Month-2 Cohort. The subjects will be enrolled before the influenza season. 
There will be no concomitant SIIV administration. 
2. Evaluate safety and immunogenicity of a second dose of RSV vaccine administered to 
the Primary Study Cohort - Stage 1 subjects, 12 months after the initial dose to determine 
whether the immune response supports annual vaccination.
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The safety and immunogenicity data from C3671001 and Stage 1 of C3671002 will guide 
the decision on whether a second dose of the RSV vaccine will be evaluated in Stage 2. If 
Stage 2 proceeds, this cohort will be known as the Primary Study Cohort - Stage 2. If 
there are no substantial differences in immune responses between the CpG/Al(OH)3 and 
Al(OH)3 formulations, then development of the CpG/Al(OH)3 formulation may cease, 
and Stage 2 will not proceed.
If the data support implementation of Stage 2, invited, consenting subjects will be 
revaccinated with the same dose and formulation of the RSV vaccine or placebo received at 
Visit 1, concomitantly with SIIV. The safety, tolerability, and immunogenicity of the second 
dose will be evaluated through 12 months after revaccination.
Additional information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the investigator’s brochure. The SRSD for the 
SIIV will be the product information for the country where the vaccine was procured.

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2. STUDY OBJECTIVES AND ENDPOINTS
Primary Objective:
Primary Endpoints:
Primary Study Cohort - Stage 1: 
To describe the safety and tolerability of 
an adjuvanted RSV vaccine given 
concomitantly with SIIV.
Primary Study Cohort - Stage 1: 

Local reactions within 14 days after Vaccination 1.

Systemic events within 14 days after Vaccination 1.

Adverse events (AEs) within 1 month after Vaccination 1.

Medically attended AEs and serious adverse events (SAEs) 
through 12 months after Vaccination 1 (from Visit 1 through 
Visit 5).
Secondary Objectives:
Secondary Endpoints:
Primary Study Cohort - Stage 1: 
To describe the immune responses 
elicited by an adjuvanted RSV vaccine
given with SIIV.
To describe the immune responses 
elicited by SIIV given alone or with an 
adjuvanted or unadjuvanted RSV 
vaccine.
Primary Study Cohort - Stage 1: 

RSV A– and RSV B–neutralizing antibody titers measured 
before and 1 month after Vaccination 1.

Hemagglutination inhibition assay (HAI) titers for all strains 
in the SIIV measured before and 1 month after Vaccination 1.
Exploratory Objectives:
Exploratory Endpoints:
Primary Study Cohort - Stage 1:
To more fully characterize the immune 
response to an adjuvanted RSV vaccine 
and to any concurrent RSV infection.
To more fully characterize the immune 
response to SIIV.
Primary Study Cohort - Stage 1: 

RSV A– and RSV B–neutralizing antibody titers measured at
1 week (peripheral blood mononuclear cell [PBMC] subjects) 
and 3, 6, and 12 months after Vaccination 1.

Plasmablast frequencies and T-cell phenotype and functional 
analysis before and 1 week after Vaccination 1 (PBMC
subjects).

Memory B-cell and T-cell frequencies and their functional 
analysis before vaccination, and 1 and 6 months after 
Vaccination 1.

Immunoglobulin G (IgG) titers against prefusion F before 
vaccination, and 1, 3, 6, and 12 months after Vaccination 1.

IgG titers to nonvaccine RSV antigens before vaccination, and 
1, 3, 6, and 12 months after Vaccination 1.

H3N2-neutralizing antibody titers measured before 
vaccination and 1 month after Vaccination 1.

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Primary Study Cohort - Stage 2:
To describe the safety and tolerability of 
a second dose of adjuvanted RSV vaccine 
given concomitantly with SIIV.
To describe the immune responses 
elicited by a second dose of an 
adjuvanted RSV vaccine given 
concomitantly with SIIV.
To more fully characterize the immune 
response to SIIV when given 
concomitantly with a second dose of 
RSV.
Primary Study Cohort - Stage 2:

Local reactions within 14 days after Vaccination 2. 

Systemic events within 14 days after Vaccination 2. 

AEs within 1 month after Vaccination 2. 

Medically attended AEs and SAEs through 12 months after 
Vaccination 2.

RSV A– and RSV B–neutralizing antibody titers measured at
1 week (PBMC subjects) and 1, 3, 6, and 12 months after 
Vaccination 2.

Plasmablast frequencies and T-cell phenotype and functional 
analysis before Vaccination 2 and 1 week after Vaccination 2 
(PBMC subjects).

Memory B-cell and T-cell frequencies and their functional 
analysis before Vaccination 2, and 1 and 6 months after 
Vaccination 2.

IgG titers against prefusion F before Vaccination 2, and 1, 3, 
6, and 12 months after Vaccination 2.

IgG titers to nonvaccine RSV antigens before Vaccination 2, 
and 1, 3, 6, and 12 months after Vaccination 2.

HAI titers for all strains in the SIIV measured before and 
1 month after Vaccination 2.

H3N2-neutralizing antibody titers measured before 
Vaccination 2 and 1 month after Vaccination 2.
RSV Vaccine Month-0, Month-2 
Cohort
To describe the safety and tolerability of 
the first and second dose of an adjuvanted 
RSV vaccine administered 2 months 
apart.
To describe the immune responses 
elicited by the first and second dose of 
adjuvanted RSV vaccine administered 2 
months apart.
RSV Vaccine Month-0, Month-2 Cohort

Local reactions within 14 days after Vaccinations 1 and 2. 

Systemic events within 14 days after Vaccinations 1 and 2. 

AEs within 1 month after Vaccinations 1 and 2. 

AEs from Vaccination 1 through 1 month after Vaccination 2.

Medically attended AEs and SAEs through 12 months after 
Vaccination 2.

RSV A– and RSV B–neutralizing antibody titers measured at 
scheduled timepoints before and after each vaccination
scheduled. 

Plasmablast frequencies and T-cell phenotype and functional 
analysis before each vaccination and 1 week after 
Vaccinations 1 and 2 (PBMC subjects).

Memory B-cell and T-cell frequencies and their functional 
analysis before each vaccination, and 1 and 6 months after 
Vaccinations 1 and 2.  

IgG titers against prefusion F at scheduled timepoints before
and after each vaccination.

IgG titers to nonvaccine RSV antigens at scheduled timepoints 
before and after each vaccination.

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3. STUDY DESIGN
This is a Phase 1/2, multicenter, randomized, placebo-controlled, observer-blind, dose- and 
formulation-finding study to describe the safety, tolerability, and immunogenicity of up to 7 
different RSV vaccine candidates with bivalent formulations (RSV A and RSV B) at 3 dose 
levels of 60 μg of the prefusion RSV F antigens 
 
 120 μg 
 
 
 and 240 μg 
 
 
 formulated with aluminum 
hydroxide (Al[OH]3) or CpG/Al(OH)3, or a 240 μg RSV vaccine 
 
alone, when administered concomitantly with SIIV, or without SIIV in a Month-0 and 
Month-2 schedule.
The dose for the RSV vaccine alone was selected based on 1-month postvaccination 
immunogenicity data from the sentinel-cohort subjects in Study C3671001 (A Phase 1/2, 
Placebo-Controlled, Randomized, Observer-Blind, Dose-Finding, First-in-Human Study to 
Describe the Safety, Tolerability, and Immunogenicity of a Respiratory Syncytial Virus 
(RSV) Vaccine in Healthy Adults; ClinicalTrials.gov identifier: NCT03529773).
The study is organized in the following cohorts:
1. Primary Study Cohort - Stage 1, will evaluate RSV vaccine doses/formulations given 
concomitantly with SIIV at Month 0. 
2. Primary Study Cohort - Stage 2, will evaluate revaccination of the Stage 1 subjects with 
a RSV vaccine and concomitant SIIV, administered at Month 12. 
3. RSV Vaccine Month-0, Month-2 Cohort will evaluate a 240 μg dose of RSV vaccine 
with CpG/Al(OH)3 given at Months 0 and 2. No concomitant SIIV will be given.
Male and female subjects 65 to 85 years of age will be enrolled. Subjects will be randomized 
equally across all dose groups in the primary cohorts. The RSV Vaccine Month-0, Month-2 
Cohort will be randomized 1:1 to receive RSV vaccine or placebo. 
Primary Study Cohort - Stage 1
Enrollment in the Primary Study Cohort - Stage 1 commenced in April 2019 and completed 
enrollment in June 2019. Approximately 250 subjects 65 to 85 years of age received 2 
intramuscular injections at Visit 1 to assess the concomitant administration of SIIV when 
given to subjects receiving one of the 3 RSV vaccine dose-level candidates formulated with 
Al(OH)3 or CpG/Al(OH)3 or the RSV vaccine–alone dose (see Section 6.1 for further 
details). 
The first 4 subjects vaccinated in the study were observed by blinded site staff for any acute 
reactions for at least 4 hours after vaccination.  Vaccination of the remaining subjects 
commenced no sooner than 48 hours after the fourth subject received his or her vaccination.
Vaccination of subjects was limited to a maximum of 6 subjects per day during the first week 
of enrollment (up to 30 vaccinated subjects in total). Follow-up will continue through 
Month 12.
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Primary Study Cohort - Stage 2
Prior to completion of Stage 1, subjects may be invited to participate in Stage 2. Safety and 
immunogenicity data obtained from the C3671001 and C3671002 studies will be used to
determine whether Stage 2 will proceed and, if so, whether all or some of the RSV 
formulations will be evaluated. 
If the data support implementation of Stage 2, consenting subjects will be revaccinated with 
the same dose and formulation of the RSV vaccine or placebo received at Visit 1,
concomitantly with SIIV. The safety, tolerability, and immunogenicity of the second dose 
will be evaluated through 12 months after revaccination.
If the data do not support the implementation of revaccination at 12 months, Stage 2 will not 
proceed. 
RSV Vaccine Month-0, Month-2 Cohort 
Approximately 62 RSV vaccine-naive subjects will be randomized 1:1 to receive either 
240 g of RSV vaccine with CpG/Al(OH)3 or placebo at Visit 1 (Month 0). At Visit 3 
(Month 2), subjects will receive a second dose of RSV vaccine or placebo as randomized at 
Visit 1. No concomitant SIIV will be given.
In Stage 1, the 240-g dose for the nonadjuvanted RSV vaccine was selected based on the 
1-month postvaccination immunogenicity data from the sentinel-cohort subjects in 
Study C3671001. The same dose will be used for the RSV Vaccine Month-0, Month-2 
Cohort.
An internal review committee (IRC) and an external data monitoring committee (E-DMC) 
will monitor safety in this study (refer to Section 9.5).
3.1. Number of Subjects
In total, approximately 312 subjects will be randomized to receive RSV vaccine at different 
dose levels and formulations or placebo at different vaccination schedules. Approximately 
250 subjects were enrolled in the Primary Study Cohort - Stage 1 and approximately 62 RSV 
vaccine-naive subjects will be enrolled in the RSV Vaccine Month-0, Month-2 Cohort (see 
Table 4 below). Of these, a subset of subjects in all cohorts will be included in the whole 
blood collection procedural requirements for the exploratory cellular analysis endpoints for 
this study. The subset will be determined at the site level. Those sites that have access to the 
appropriate specimen-processing laboratories will provide all subjects for the PBMC 
collection subset.  It is anticipated that the subjects from the selected sites will constitute 
approximately 1/3 of the total number of randomized subjects.
Subjects who withdraw or are withdrawn from the study after randomization will not be 
replaced, regardless of the reason for withdrawal.

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Table 4.
Randomization of Subjects by Dose and Formulation
Primary Study Cohort
Approximate Number of Males and 
Females 65 to 85 Years of Age
Dose/Formulation
Stage 1 / Stage 2
Originally Planned 
Study Target
Vaccinated in 
Stage 1
60 g
RSV+Al(OH)3
SIIV
(Month 0/Month 12 a)
39
~31 b
RSV+CpG/Al(OH)3
SIIV
(Month 0/Month 12 a)
39
~31 b
120 g
RSV+Al(OH)3
SIIV
(Month 0/Month 12 a)
39
~31 b
RSV+CpG/Al(OH)3
SIIV
(Month 0/Month 12 a)
39
~31 b
240 g
RSV+Al(OH)3
SIIV
(Month 0/Month 12 a)
39
~31 b
RSV+CpG/Al(OH)3
SIIV
(Month 0/Month 12 a)
39
~31 b
240 g
RSV
SIIV
(Month 0/Month 12 a)
39
~31 b
Placebo
SIIV
(Month 0/Month 12 a)
39
~31 b
     Total
312
250
     RSV Vaccine Month-0, Month-2 Cohort
Target
240 g
RSV+CpG/Al(OH)3
(Month 0/Month 2)
31
Placebo
(Month 0/Month 2)
31
Total
62
Total study size
312
Abbreviations: Al(OH)3 = aluminum hydroxide; RSV = respiratory syncytial virus vaccine; SIIV = seasonal 
inactivated influenza vaccine.
a.
Primary Study Cohort - Stage 2 is contingent on supporting data from Stage 1 and applies to 
invited/consenting subjects only.
b.
Approximate number of subjects vaccinated in each dose/formulation group are shown, actual numbers per 
group will be known after unblinding.

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3.2. Duration of Subject Participation
Subjects enrolled in the Primary Study Cohort - Stage 1 will participate in the study for 
approximately 12 months, or up to approximately 24 months if completing Stage 2.
Subjects enrolled in the RSV Vaccine Month-0, Month-2 Cohort will participate in the study 
for approximately 14 months. 
3.3. Duration of Study
The study will last approximately 26 months.
The study is dependent on SIIV availability and access to subjects who have not received 
SIIV within the preceding 6 months. It is anticipated that the study will be conducted in the 
same geographic location; however, if required for operational reasons, this study may be 
conducted in more than 1 geographic location over more than 1 influenza season.
4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects 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 subject is suitable for this protocol.
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document (ICD) indicating 
that the subject has been informed of all pertinent aspects of the study.
2.
Healthy adults who are determined by medical history, physical examination, and 
clinical judgment of the investigator to be eligible for inclusion in the study.
Note: Healthy subjects with preexisting stable disease, defined as disease not requiring 
significant change in therapy or hospitalization for worsening disease within 6 weeks before 
enrollment, can be included.
3.
Willing and able to comply with scheduled visits, vaccination plan, laboratory tests, and 
other study procedures.
4.
Male and nonchildbearing-potential female adults 65 to 85 years of age at the time of 
enrollment (signing of the ICD).

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Note: Female subjects of nonchildbearing potential must meet at least 1 of the following 
criteria:

Postmenopausal status, defined as follows: cessation of regular menses for at least 
12 consecutive months with no alternative pathological or physiological cause; status 
may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming 
the postmenopausal state;

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are considered to be 
of childbearing potential.
5. Subjects must have received the primary vaccination (RSV vaccine or placebo) at Visit 1 
and have signed and dated the ICD for participating in the revaccination stage (applies to 
Primary Study Cohort - Stage 2 subjects).
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
subjects who are Pfizer employees, including their family members, directly involved in 
the conduct of the study.
2. Participation in other studies involving investigational product within 28 days prior to 
study entry and/or during study participation.
3. Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), 
or hepatitis B virus (HBV).
4. Previous vaccination with any licensed or investigational RSV vaccine before 
enrollment into the study, or planned receipt throughout the study of nonstudy RSV 
vaccine
5. Vaccination with any influenza vaccine within 6 months (182 days) before 
investigational product administration (applies to Primary Study Cohort - Stages 1 and 
2).
6. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product(s), including 
natural rubber latex. In addition, a history of severe allergic reaction (eg, anaphylaxis) 
to any substance, including documented allergy to egg proteins (egg or egg products) or 
chicken proteins.

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7. Subjects with known or suspected immunodeficiency, as determined by history and/or 
laboratory/physical examination.
8. Subjects receiving treatment with immunosuppressive therapy, including cytotoxic 
agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned 
receipt throughout the study.  If systemic corticosteroids have been administered short 
term (<14 days) for treatment of an acute illness, subjects should not be enrolled into 
the study until corticosteroid therapy has been discontinued for at least 28 days before 
investigational product administration. Inhaled/nebulized, intra-articular, intrabursal, or 
topical (epidural, skin, or eyes) corticosteroids are permitted.
9. Subjects with a history of autoimmune disease or an active autoimmune disease 
requiring therapeutic intervention including but not limited to: systemic or cutaneous 
lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré
syndrome, multiple sclerosis, Sjögren syndrome, idiopathic thrombocytopenic purpura, 
autoimmune glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal 
arteritis), psoriasis, and insulin-dependent diabetes mellitus (type 1).
10. Receipt of any blood/plasma products or immunoglobulin, from 60 days before 
investigational product administration or planned receipt throughout the study.
11. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
12. Female subjects of childbearing potential or who are pregnant or breastfeeding; fertile 
male subjects who are unwilling to use a highly effective method of contraception for at 
least 28 days after the last dose of investigational product.
13. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the subject inappropriate for entry into this study.
14. Planned donation of blood volumes of approximately 470 mL within 12 weeks after 
Vaccination 1 (applies to subjects having additional blood drawn for cellular assays).
4.3. Criteria for Temporarily Delaying Vaccine Administration
The following conditions are temporary or self-limiting and a subject may be vaccinated 
once the condition(s) has/have resolved and no other exclusion criteria are met.

Current febrile illness (oral temperature 100.4F [38C]) or other acute illness within 
48 hours before investigational product administration.

Any acute respiratory illness within 14 days before investigational product 
administration.

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
Receipt of any inactivated vaccine within 14 days or any live vaccine within 28 days 
before or anticipated receipt of any vaccine within the 14 days after investigational 
product administration.

Receipt of short-term (<14 days) systemic corticosteroids.  Investigational product 
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical (epidural, 
skin, or eyes) corticosteroids are permitted.
4.4. Lifestyle Requirements
4.4.1. Contraception
All fertile male subjects who are, in the opinion of the investigator, sexually active and at risk 
for pregnancy with their partner(s) must agree to use a highly effective method of 
contraception consistently and correctly at least 28 days after the last dose of investigational 
product.  The investigator or his or her designee, in consultation with the subject, will 
confirm that the subject has selected an appropriate method of contraception for the 
individual subject and his partner from the permitted list of contraception methods 
(see below) and will confirm that the subject has been instructed in its consistent and correct 
use.  At time points indicated in the Schedule of Activities, the investigator or designee will 
inform the subject of the need to use highly effective contraception consistently and correctly 
and document the conversation and the subject’s affirmation in the subject’s chart (subjects
need to affirm their consistent and correct use of at least 1 of the selected methods of 
contraception).  In addition, the investigator or designee will instruct the subject to call 
immediately if the selected contraception method is discontinued or if pregnancy is known or 
suspected in the subject’s partner.
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:

Established use of hormonal methods of contraception associated with inhibition of 
ovulation (eg, oral, inserted, injected, implanted, transdermal), provided the subject or 
male subject’s female partner plans to remain on the same treatment throughout the entire 
study and has been using that hormonal contraceptive for an adequate period of time to 
ensure effectiveness. Correctly placed intrauterine device (IUD) or hormone-releasing
intrauterine system (IUS).

Male condom or female condom used WITH a separate spermicide product (ie, foam, gel, 
film, cream, or suppository). For countries where spermicide is not available or condom 
plus spermicide is not accepted as highly effective contraception, this option is not 
appropriate.

Male sterilization with absence of sperm in the postvasectomy ejaculate.

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
Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the subject.
4.5. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card.  The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study. The contact number can also be used by investigator
staff if they are seeking advice on medical questions or problems; however, it should be used
only in the event that the established communication pathways between the investigator site 
and the study team are not available. It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigator site.
5. INVESTIGATIONAL PRODUCTS
For the purposes of this study, and per International Council for Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).
For this study, the investigational products are RSV vaccine and placebo (saline control).
Commercially available SIIV will also be provided by the sponsor.
5.1. Allocation to Investigational Product
Allocation of subjects to vaccine groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  Site staff will 
be required to enter or select information including but not limited to the user’s identification 
(ID) and password, the protocol number, and the subject number.

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The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system.
5.1.1. Blinding of Study Site Personnel
This is an observer-blinded study as the physical appearance of the RSV vaccine candidates
and placebo may differ. SIIV will be administered in an open-label fashion.
The subject, investigator, study coordinator, and other site staff will be blinded. At the study 
site, only the dispenser(s)/administrator(s) are unblinded.
Contact between the unblinded dispenser(s)/administrator(s) and study subjects should be 
kept to a minimum.  The investigator, study coordinator, and any site staff other than the 
unblinded dispenser(s)/administrator(s) must not be allowed to know the investigational 
product assigned to any study subject and must not be allowed to see the investigational 
product.
5.1.2. Blinding of the Sponsor
The sponsor study team members will be blinded to the vaccine assigned/received by all 
subjects, from subject randomization up until 1 month after vaccination for the Primary 
Study Cohort - Stage 1 and from subject randomization up until 1 month after the second 
vaccination for the RSV Vaccine Month-0, Month-2 Cohort, when safety and 
immunogenicity data are available for analysis.
Laboratory personnel performing the immunologic assays will remain blinded to vaccine 
assigned/received throughout the study.
Certain sponsor personnel not directly involved in the conduct of the study will review safety
data as defined in an IRC charter per Pfizer standard operating procedures (SOPs).
Unblinded sponsor personnel who are not part of the study team will be assigned to assess 
whether a stopping rule is triggered (see Section 7.4) for details) and for ongoing safety 
review.
Those study team members who are involved in ensuring that protocol requirements for 
investigational product handling, allocation, and administration are fulfilled at the site 
(eg, study manager; clinical research associates [CRAs]) will be unblinded for the duration of 
the study.
5.2. Breaking the Blind
At the initiation of the study, the investigator will be instructed on the method for breaking 
the blind for an individual subject.  The method will be an electronic process.  Blinding codes 
should be broken only in exceptional circumstances when knowledge of the actual treatment 
code is absolutely essential for further management of the subject.  Investigators are 
encouraged to discuss with a member of the study team if they believe that unblinding is 
necessary.  When the blinding code is broken, the reason must be fully documented and 
entered on the case report form (CRF).

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5.3. Subject Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
5.4. Investigational Product Supplies
5.4.1. Dosage Form(s) and Packaging
5.4.1.1. Respiratory Syncytial Virus Stabilized Prefusion F Subunit Vaccine
Each lyophilized vial of the RSV vaccine drug product is supplied as a mixture of equal 
 
There are 3 different presentations of RSV drug product.  The Al(OH)3- and 
CpG/Al(OH)3-containing formulations consist of 3 different dose levels of lyophilized RSV 
antigen (60 μg, 120 μg, and 240 μg).  The RSV antigens without Al(OH)3 or CpG/Al(OH)3
will consist of a single dose level (240 μg). The lyophilized cake is reconstituted with one of 
3 diluents:  a sterile suspension of Al(OH)3 in water for injection, a sterile suspension of
CpG/Al(OH)3, or sterile water for injection.
The fill volumes of the drug product vial and diluent vial are designed such that the intended 
vaccine dose is delivered in a 0.5-mL injection volume.
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5.4.1.2. Seasonal Inactivated Influenza Vaccine
Commercially available high-dose (HD) trivalent SIIV (if available) or quadrivalent SIIV 
will be used in the Primary Study Cohort - Stage 1 and Stage 2. 
Investigational sites will be notified which commercially available SIIV will be provided 
prior to the start of enrollment.
The World Health Organization may change its influenza vaccine reference strain 
recommendations from one northern or southern hemisphere influenza season to the next and 
may recommend more than 1 reference strain for each type A subtype or type B lineage; 
different national regulatory authorities may select different reference strains in a single 
season; and different SIIV manufacturers may choose different influenza vaccine strains that 
are antigenically like the selected reference strains.  Therefore, the influenza vaccines that are 
available in different seasons and in different countries may have different strain 
compositions, and this study may necessarily include more than 1 SIIV formulation.
5.4.1.3. Placebo
The placebo will be a sterile normal saline solution for injection (0.9% sodium chloride 
injection, in a 0.5-mL dose).
Placebo will be provided by the sponsor to each study site.  The placebo will be packaged 
within cartons labeled by Pfizer or its designee in accordance with current guidelines and 
applicable local and legal regulatory requirements.
5.4.2. Preparation and Dispensing
Investigational product preparation and dosing information will be provided in the 
investigational product (IP) manual.
The investigational product will be dispensed using an IRT investigational product 
management system.
5.5. Administration
Vaccine will be administered in the upper deltoid muscle by the unblinded administrator.

Primary Study Cohort - Stage 1
Subjects will receive 2 injections at Visit 1 (Day 1) in accordance with the assigned 
randomized treatment; see Table 6 below for administration guidance.

Primary Study Cohort - Stage 2
Subjects will receive 2 injections at Visit 1 (Day 1) and 2 injections at Visit 5 (Month 12) in 
accordance with the assigned randomized treatment; see Table 6 below for administration 
guidance.

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
RSV Vaccine Month-0, Month-2 Cohort 
Subjects will receive a single injection at Visit 1 (Month 0) and at Visit 3 (Month 2) in 
accordance with the assigned randomized treatment; see Table 6 below for administration 
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.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff 
(eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or medical 
assistant) as allowed by local, state, and institutional guidance.
Investigational product administration details will be recorded on the CRF.
Table 6.
Location of Intramuscular Injection
Product Administered
Location of Injection
Primary Study Cohort - Stage 1 and Stage 2
RSV+Al(OH)3
SIIV
Left deltoid muscle
Right deltoid muscle
RSV+CpG/Al(OH)3
SIIV
Left deltoid muscle
Right deltoid muscle
RSV
SIIV
Left deltoid muscle
Right deltoid muscle
Placebo
SIIV
Left deltoid muscle
Right deltoid muscle
RSV Vaccine Month-0, Month-2 Cohort
RSV+CpG/Al(OH)3 or placebo
Left deltoid muscle
Abbreviations:  Al(OH)3 = aluminum hydroxide; RSV = respiratory syncytial virus vaccine;
SIIV = seasonal inactivated influenza vaccine.
5.6. Investigational Product Storage
SIIV, investigational product, diluent, and placebo will be shipped at +2C to +8C to the 
study site after required regulatory and legal documents have been received by the sponsor.
Upon receipt at the study site, SIIV, investigational product, diluent, and placebo should be 
immediately transferred to a +2C to +8C temperature-monitored refrigerator for storage.

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The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products and SIIV are stored in a secured area with controlled access under 
required storage conditions and in accordance with applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels.
See the IP manual for storage conditions of the product once reconstituted.
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations 
(as applicable, including frozen, refrigerated, and/or room-temperature products).  This 
should be captured from the time of investigational product receipt throughout the study.  
Even for continuous-monitoring systems, a log or site procedure that ensures active 
evaluation for excursions should be available.
The intent is to ensure that the minimum and maximum temperature is checked each business 
day to confirm that no excursion occurred since the last evaluation and to provide the site 
with the capability to store or view the minimum/maximum temperature for all nonworking 
days upon return to normal operations.  The operation of the temperature-monitoring device 
and storage unit (for example, refrigerator), as applicable, should be regularly inspected to 
ensure they are maintained in working order.
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery. The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer.
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion.  Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation.  Specific details regarding information the site should report 
for each excursion will be provided to the site.
5.7. Investigational Product Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record.

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5.7.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
5.8. Concomitant Treatment(s)
5.8.1. Prohibited Nonstudy Vaccines Prior to the Study

Licensed or investigational RSV vaccines at any time.

Receipt of any inactivated vaccine within 14 days or any live vaccine within 28 days 
before investigational product administration.

Vaccination with any influenza vaccine within 6 months (182 days) before 
investigational product administration.
5.8.2. Prohibited Nonstudy Vaccines and Medications During the Study

Nonstudy investigational vaccines, investigational drugs, or investigational medical 
devices are prohibited during the course of the study.

Vaccination with any influenza vaccine within 6 months (182 days) before 
investigational product administration (applicable to Primary Study Cohort - Stage 2 
subjects).

Licensed or investigational RSV vaccines, blood/plasma products, or immunoglobulins 
are prohibited during the course of the study.

Immunosuppressive therapy is prohibited during the study with the exception of 
inhaled/nebulized, intra-articular, intrabursal, or topical (epidural, skin, or eyes) 
corticosteroids, which are permitted.

Unless considered medically necessary, no vaccines should be administered until at least
28 days after investigational product administration.

Prophylactic antipyretics and other pain medication to prevent symptoms associated with 
investigational product administration are not permitted.
5.8.3. Permitted Nonstudy Vaccines and Medications During the Study

Licensed influenza vaccine may be given during the study starting after the blood sample 
has been taken at the 1-month postvaccination visits (applicable to Primary Study 
Cohort - Stage 1 and Stage 2). 

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
For the RSV Vaccine Month-0, Month-2 Cohort, nonstudy licensed influenza vaccine 
may be given after Visit 3. 

If medically necessary (eg, pandemic), influenza vaccine may be given at any time.

Inhaled/nebulized, intra-articular, intrabursal, or topical (epidural, skin, or eyes) 
corticosteroids are permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during subject participation in the 
study.

Medication other than that described as prohibited in Section 5.8.2 required for treatment 
of preexisting stable conditions is permitted.
5.8.4. Recording Nonstudy Vaccinations and Concomitant Medications
The name and date of administration for all nonstudy vaccinations received from the time of 
signing of the ICD will be collected and recorded in the CRF. Concomitant medications will 
be assessed but not documented on the CRF.
6. STUDY PROCEDURES
6.1. Primary Study Cohort - Stage 1
6.1.1. Primary Study Cohort - Stage 1, Visit 1: Vaccination (Day 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the subject. Each signature on the 
ICD must be personally dated by the signatory. The investigator or his or her designee will 
also sign the ICD. A copy of the signed and dated ICD must be given to the subject. The 
source data must reflect that the informed consent was obtained before participation in the 
study.
It is anticipated that the procedures below will be conducted in a stepwise manner; ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.

Assign single subject identifier using the IRT system.

Obtain the subject’s demography (including date of birth, sex, race, and ethnicity). The 
date of birth will be collected to critically evaluate the immune response and safety 
profile by age.

Assess and record tobacco usage.

Obtain any medical history of clinical significance.

Obtain details of any medications currently taken.

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
Perform physical examination including vital signs (weight, height, oral temperature, 
heart rate, and seated blood pressure), evaluating any clinically significant abnormalities 
within the following body systems: general appearance; skin; head, eyes, ears, nose, and 
throat; heart; lungs; abdomen; musculoskeletal; extremities; neurological; and lymph 
nodes.

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met.

Record nonstudy vaccinations as described in Section 5.8.4.

Ensure that the subject meets none of the temporary delay criteria as described in 
Section 4.3.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Obtain the subject’s randomization number and investigational product container number 
using the IRT system. Either blinded site staff or unblinded site staff member may obtain 
this information.

Prior to vaccination, collect a blood sample of approximately 50 mL for antibody 
assessment.

Prior to vaccination, collect a blood sample of approximately 100 mL for cellular assays 
(from consenting PBMC subjects at designated PBMC collection sites only; see 
Section 3.1).

Unblinded site staff member(s) will dispense/administer a 0.5-mL injection of 
investigational product into the deltoid muscle of the left arm and a 0.5-mL injection of 
SIIV into the deltoid muscle of the right arm (see Table 6).  Please refer to the IP manual 
for further instruction on this process.

The first 4 subjects vaccinated in the study must be observed by blinded site staff for any 
acute reactions for at least 4 hours after vaccination.  For subjects enrolled thereafter, 
blinded site staff must observe the subject for at least 30 minutes after investigational 
product administration for any acute reactions.  Record any acute reactions (including 
time of onset) in the subject’s source documents and on the AE page of the CRF, and on 
an SAE form as applicable.

Record AEs as described in Section 8.

Issue a measuring device to measure local reactions at the injection site of the left arm 
and a digital thermometer for recording daily temperatures and provide instructions on 
their use.

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
Issue the subject an electronic diary (e-diary) and provide instructions on its completion.  
Ask the subject to complete the e-diary from Day 1 to Day 14, with Day 1 being the day 
of vaccination.

Ask the subject to contact the site staff or investigator immediately if he or she 
experiences any of the following from Day 1 to Day 14 after vaccination (where Day 1 is 
the day of vaccination) to determine if an unscheduled reactogenicity visit is required: 

Fever 39.0C (102.1F).

Redness or swelling at the injection site on the left arm measuring greater than 
10 cm (>20 measuring device units).

Any blackening of the skin (necrosis) at the injection site on the left arm.

Any peeling/scaling of the skin (exfoliative dermatitis) at the injection site on the 
left arm.

Severe pain at the injection site on the left arm.

Any severe systemic event.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Remind subjects that study staff may contact them to obtain additional information on 
events entered into the e-diary.

Schedule an appointment for the subject to return for the next study visit.

Remind the subject to bring the completed e-diary to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate subject compliance and as part of the ongoing safety 
review. Daily review is optimal during the active diary period.
6.1.2. Primary Study Cohort - Stage 1, Visit 2: 1-Week Follow-up Visit (6-8 Days After 
Visit 1) (applicable to consenting PBMC subjects at PBMC collection sites only)

Review the subject’s e-diary data.

Record nonstudy vaccinations as described in Section 5.8.4.

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
Confirm understanding of and compliance with protocol requirements for contraception
(male subjects only).

Collect a blood sample of approximately 50 mL for antibody assessment.

Collect a blood sample of approximately 50 mL for cellular assays.

Record AEs as described in Section 8.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Schedule an appointment for the subject to return for the next study visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
6.1.3. Primary Study Cohort - Stage 1, Visit 2: 1-Month Follow-up Visit (28-35 Days 
After Visit 1) (applicable to all subjects)

Ensure that the subject meets none of the subject withdrawal criteria as described in 
Section 6.5.

Review the subject’s e-diary data and collect the e-diary. Collect stop dates of any 
e-diary events ongoing on the last day that the e-diary was completed and record stop 
dates in the CRF if required.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Collect a blood sample of approximately 50 mL for antibody assessment.

Collect a blood sample of approximately 50 mL for cellular assays (from consenting 
PBMC subjects at PBMC collection sites only).

Record nonstudy vaccinations as described in Section 5.8.4.

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

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6.1.4. Primary Study Cohort - Stage 1, Visit 3: 3-Month Follow-up Visit (84-105 Days 
After Visit 1)

Ensure that the subject meets none of the withdrawal criteria as described in Section 6.5.

Collect a blood sample of approximately 50 mL for antibody assessment.

Record nonstudy vaccinations as described in Section 5.8.4.

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
6.1.5. Primary Study Cohort - Stage 1, Visit 4: 6-Month Follow-up Visit (168-210 Days 
After Visit 1)

Ensure that the subject meets none of the subject withdrawal criteria as described in 
Section 6.5.

Collect a blood sample of approximately 50 mL for antibody assessment.

Collect a blood sample of approximately 50 mL for cellular assays (from consenting 
PBMC subjects at PBMC collection sites only).

Record nonstudy vaccinations as described in Section 5.8.4.

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRF.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
6.1.6. Primary Study Cohort - Stage 1, Visit 5: 12-Month Follow-up Visit (300-400 Days 
After Visit 1)
For subjects not participating in Stage 2:

Collect a blood sample of approximately 25 mL for antibody assessment.

Record nonstudy vaccinations as described in Section 5.8.4.

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
Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
For the Primary Study Cohort - Stage 1 subjects invited and consenting to Stage 2 of this 
study, follow the procedures listed in Section 6.2.
6.2. Primary Study Cohort - Stage 2
6.2.1. Primary Study Cohort - Stage 2, Visit 5: 12-Month Follow-up Visit (300-400 Days 
After Visit 1)
Before any study-related procedures are performed, voluntary, written study-specific 
informed consent for the revaccination stage will be obtained from the subject. Each 
signature on the ICD must be personally dated by the signatory. The investigator or his or 
her designee will also sign the Primary Study Cohort - Stage 2 ICD. A copy of this signed 
and dated ICD must be given to the subject. The source data must reflect that this informed 
consent was obtained before participation in the second stage of this study. Ideally, informed 
consent will be obtained prior to this visit. 
It is anticipated that the procedures below will be conducted in a stepwise manner. Ensure 
that the procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.

Perform physical examination including vital signs (weight, oral temperature, heart rate, 
and seated blood pressure), evaluating any clinically significant abnormalities within the 
following body systems: general appearance; skin; head, eyes, ears, nose, and throat; 
heart; lungs; abdomen; musculoskeletal; extremities; neurological; and lymph nodes.

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met.

Record nonstudy vaccinations as described in Section 5.8.4.

Ensure that the subject meets none of the temporary delay criteria as described in 
Section 4.3.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Obtain the subject’s investigational product container number using the IRT system.
Either blinded site staff or unblinded site staff members may obtain this information.

Prior to vaccination, collect a blood sample of approximately 25 mL for antibody
assessment.

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
Prior to vaccination, collect a blood sample of approximately 100 mL for cellular assays 
(from consenting PBMC subjects at PBMC collection sites only; see Section 3.1).

Unblinded site staff member(s) will dispense/administer a 0.5-mL injection of 
investigational product into the deltoid muscle of the left arm and a 0.5-mL injection of 
SIIV into the deltoid muscle of the right arm (see Table 6).  Please refer to the IP manual 
for further instructions on this process.

Blinded site staff must observe the subject for at least 30 minutes after investigational 
product administration for any acute reactions.  Record any acute reactions (including 
time of onset) in the subject’s source documents and on the AE page of the CRF, and on 
an SAE form if applicable.

Record AEs as described in Section 8.

Issue a measuring device to measure local reactions at the injection site of the left arm 
and a digital thermometer for recording daily temperatures and provide instructions on 
their use.

Issue the subject an e-diary and provide instructions on its completion.  Ask the subject to 
complete the e-diary from Day 1 to Day 14, with Day 1 being the day of vaccination.
Review the e-diary data in Trial Manager on a daily basis for the 14-day postvaccination 
period. Follow up on all severe reactions as described in Section 7.3.1.

Ask the subject to contact the site staff or investigator immediately if he or she 
experiences any of the following from Day 1 to Day 14 after vaccination (where Day 1 is 
the day of vaccination) to determine if an unscheduled reactogenicity visit is required: 

Fever 39.0C (102.1F).

Redness or swelling at the injection site on the left arm measuring greater than 
10 cm (>20 measuring device units).

Any blackening of the skin (necrosis) at the injection site on the left arm.

Any peeling/scaling of the skin (exfoliative dermatitis) at the injection site on the 
left arm.

Severe pain at the injection site on the left arm.

Any severe systemic event.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

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
Schedule an appointment for the subject to return for the next study visit. Subjects 
consenting to PBMC collection will attend 1 week later for Visit 6A. All other subjects 
will attend Visit 6.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
6.2.2. Primary Study Cohort - Stage 2, Visit 6A: 1-Week Revaccination Follow-up Visit 
(6 to 8 Days After Visit 5) (applies to subjects consenting to PBMC collection at PBMC
collection sites only)

Review the subject’s e-diary data.

Record nonstudy vaccinations as described in Section 5.8.4.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Collect a blood sample of approximately 50 mL for cellular assays.

Record AEs as described in Section 8.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Schedule an appointment for the subject to return for the next study visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
6.2.3. Primary Study Cohort - Stage 2, Visit 6: 1-Month Revaccination Follow-up Visit 
(28-35 Days After Visit 5) (applies to all subjects)

Record nonstudy vaccinations as described in Section 5.8.4.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Collect a blood sample of approximately 25 mL for antibody assessment.

Collect a blood sample of approximately 50 mL for cellular assays (from consenting 
PBMC subjects at PBMC collection sites only).

Review the subject’s e-diary data and collect the e-diary.  Collect stop dates of any 
e-diary events ongoing on the last day that the e-diary was completed and record stop 
dates in the CRF if required.

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
Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
6.2.4. Primary Study Cohort - Stage 2, Visit 7: 3-Month Revaccination Follow-up Visit 
(84 to 105 Days After Visit 5) (applies to all subjects)

Record nonstudy vaccinations as described in Section 5.8.4.

Collect a blood sample of approximately 25 mL for antibody assessment.

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
6.2.5. Primary Study Cohort - Stage 2, Visit 8: 6-Month Revaccination Follow-up Visit 
(168 to 210 Days After Visit 5) (applies to all subjects)

Record nonstudy vaccinations as described in Section 5.8.4.

Collect a blood sample of approximately 25 mL for antibody assessment.

Collect a blood sample of approximately 50 mL for cellular assays (from consenting 
PBMC subjects at PBMC collection sites only).

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRF.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

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6.2.6. Primary Study Cohort - Stage 2, Visit 9: 12-Month Revaccination Follow-up Visit 
(350 to 378 Days After Visit 5) (applies to all subjects)

Record nonstudy vaccinations as described in Section 5.8.4.

Collect a blood sample of approximately 25 mL for antibody assessment.

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
6.3. RSV Vaccine Month-0, Month-2 Cohort 
6.3.1. RSV Vaccine Month-0, Month-2 Cohort, Visit 1: Vaccination 1 (Day 1)
Before enrollment and before any study-related procedures are performed, voluntary, written 
study-specific informed consent will be obtained from the subject. Each signature on the 
ICD must be personally dated by the signatory. The investigator or his or her designee will 
also sign the RSV Vaccine Month-0, Month-2 Cohort ICD. A copy of the signed and dated 
ICD must be given to the subject. The source data must reflect that the informed consent was 
obtained before participation in the study.
It is anticipated that the procedures below will be conducted in a stepwise manner. Ensure 
that the procedures listed prior to administration of the vaccine are conducted prior to 
vaccination.

Assign single subject identifier using the IRT system.

Obtain the subject’s demography (including date of birth, sex, race, and ethnicity). The 
date of birth will be collected to critically evaluate the immune response and safety 
profile by age.

Obtain any medical history of clinical significance.

Assess and record tobacco usage.

Record all current medications in source documents.

Perform physical examination including vital signs (weight, height, oral temperature, 
heart rate, and seated blood pressure), evaluating any clinically significant abnormalities 
within the following body systems: general appearance; skin; head, eyes, ears, nose, and 
throat; heart; lungs; abdomen; musculoskeletal; extremities; neurological; and lymph 
nodes.

Record nonstudy vaccinations as described in Section 5.8.4.

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
Ensure and document that all the inclusion criteria and none of the exclusion criteria are 
met.

Ensure that the subject meets none of the temporary delay criteria as described in 
Section 4.3.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Obtain the subject’s randomization number and investigational product container number 
using the IRT system. Either blinded site staff or unblinded site staff members may 
obtain this information.

Prior to vaccination, collect a blood sample of approximately 25 mL for antibody
assessment.

Prior to vaccination, collect a blood sample of approximately 100 mL for cellular assays 
(from consenting PBMC subjects at PBMC collection sites only; see Section 3.1).

Unblinded site staff member(s) will dispense/administer a 0.5-mL injection of 
investigational product into the deltoid muscle of the left arm (see Table 6).  Please refer 
to the IP manual for further instruction on this process.

Observe the subject for at least 30 minutes after investigational product administration for 
any acute reactions.  Record any acute reactions (including time of onset) in the subject’s 
source documents and on the AE page of the CRF, and on an SAE form if applicable.

Record AEs as described in Section 8.

Issue a measuring device to measure local reactions at the injection site of the left arm 
and a digital thermometer for recording daily temperatures and provide instructions on 
their use.

Issue the subject an e-diary and provide instructions on its completion.  Ask the subject to 
complete the e-diary from Day 1 to Day 14, with Day 1 being the day of Vaccination 1.
Review the e-diary data in Trial Manager on a daily basis for the 14-day postvaccination 
period. Follow up on all severe reactions as described in Section 7.3.1.

Ask the subject to contact the site staff or investigator immediately if he or she 
experiences any of the following from Day 1 to Day 14 after Vaccination 1 to determine 
if an unscheduled reactogenicity visit is required: 

Fever 39.0C (102.1F).

Redness or swelling at the injection site on the left arm measuring greater than 
10 cm (>20 measuring device units).

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
Any blackening of the skin (necrosis) at the injection site on the left arm.

Any peeling/scaling of the skin (exfoliative dermatitis) at the injection site on the 
left arm.

Severe pain at the injection site on the left arm.

Any severe systemic event.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Remind subjects that study staff may contact them to obtain additional information on 
events entered into the e-diary.

Schedule an appointment for the subject to return for the next study visit.

Remind the subject to bring the completed e-diary to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate subject compliance and as part of the ongoing safety 
review. Daily review is optimal during the active diary period.
6.3.2. RSV Vaccine Month-0, Month-2 Cohort, Visit 2A: 1-Week Follow-up Visit (6 to 8 
Days After Visit 1) (applies to subjects consenting to PBMC collection at PBMC collection 
sites only)

Review the subject’s e-diary data.

Record nonstudy vaccinations as described in Section 5.8.4.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Collect a blood sample of approximately 50 mL for cellular assays.

Record AEs as described in Section 8.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Schedule an appointment for the subject to return for the next study visit.

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
Complete the source documents.

The investigator or an authorized designee completes the CRFs.
6.3.3. RSV Vaccine Month-0, Month-2 Cohort, Visit 2: 1-Month Follow-up Visit (28 to 
35 Days After Visit 1) (applies to all subjects)

Review the subject’s e-diary data and collect the e-diary.  Collect stop dates of any 
e-diary events ongoing on the last day that the e-diary was completed and record stop 
dates in the CRF if required.

Record nonstudy vaccinations as described in Section 5.8.4.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Collect a blood sample of approximately 25 mL for antibody assessment.

Collect a blood sample of approximately 50 mL for cellular assays (from consenting 
PBMC subjects at PBMC collection sites only).

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
6.3.4. RSV Vaccine Month-0, Month-2 Cohort, Visit 3: Vaccination 2 Visit (54 to 66
Days After Visit 1) (applies to all subjects)

Record nonstudy vaccinations as described in Section 5.8.4.

Ensure that the subject meets none of the temporary delay criteria as described in 
Section 4.3.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Prior to vaccination, collect a blood sample of approximately 25 mL for antibody
assessment.

Prior to vaccination, collect a blood sample of approximately 50 mL for cellular assays 
(from consenting PBMC subjects at PBMC collection sites only; see Section 3.1).

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
Unblinded site staff member(s) will dispense/administer a 0.5-mL injection of 
investigational product into the deltoid muscle of the left arm (see Table 6).  Please refer 
to the IP manual for further instruction on this process.

Observe the subject for at least 30 minutes after investigational product administration for 
any acute reactions.  Record any acute reactions (include time of onset) in the subject’s 
source documents and on the AE page of the CRF, and on an SAE form as applicable.

Record AEs as described in Section 8.

Issue a measuring device to measure local reactions at the injection site of the left arm 
and a digital thermometer for recording daily temperatures and provide instructions on 
their use.

Issue the subject an e-diary and provide instructions on its completion.  Ask the subject to 
complete the e-diary from Day 1 to Day 14, with Day 1 being the day of Vaccination 2.
Review the e-diary data in Trial Manager on a daily basis for the 14-day postvaccination 
period. Follow up on all severe reactions as described in Section 7.3.1.

Ask the subject to contact the site staff or investigator immediately if he or she 
experiences any of the following from Day 1 to Day 14 after Vaccination 2 to determine 
if an unscheduled reactogenicity visit is required: 

Fever 39.0C (102.1F).

Redness or swelling at the injection site on the left arm measuring greater than 
10 cm (>20 measuring device units).

Any blackening of the skin (necrosis) at the injection site on the left arm.

Any peeling/scaling of the skin (exfoliative dermatitis) at the injection site on the 
left arm.

Severe pain at the injection site on the left arm.

Any severe systemic event.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Remind subjects that study staff may contact them to obtain additional information on 
events entered into the e-diary.

Schedule an appointment for the subject to return for the next study visit.

Remind the subject to bring the completed e-diary to the next visit.

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
Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate subject compliance and as part of the ongoing safety 
review. Daily review is optimal during the active diary period.
6.3.5. RSV Vaccine Month-0, Month-2 Cohort, Visit 4Aa: 1-Week Post-Vaccination 2
Follow-up Visit (6 to 8 Days After Visit 3) (applies to subjects consenting to PBMC 
collection at PBMC collection sites only)

Review the subject’s e-diary data.

Record nonstudy vaccinations as described in Section 5.8.4.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Collect a blood sample of approximately 50 mL for cellular assays.

Record AEs as described in Section 8.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Schedule an appointment for the subject to return for the next study visit.

Remind the subject to bring the completed e-diary to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
6.3.6. RSV Vaccine Month-0, Month-2 Cohort, Visit 4: 1-Month Post-Vaccination 2 
Follow-up Visit (28 to 35 Days After Visit 3) (applies to all subjects)

Review the subject’s e-diary data and collect the e-diary.  Collect stop dates of any 
e-diary events ongoing on the last day that the e-diary was completed and record stop 
dates in the CRF if required.

Record nonstudy vaccinations as described in Section 5.8.4.

Confirm understanding of and compliance with protocol requirements for contraception 
(male subjects only).

Collect a blood sample of approximately 25 mL for antibody assessment.

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
Collect a blood sample of approximately 50 mL for cellular assays (from consenting 
PBMC subjects at PBMC collection sites only).

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
6.3.7. RSV Vaccine Month-0, Month-2 Cohort, Visit 5: 6-Month Follow-up Visit (168 to 
210 Days After Visit 3) (applies to all subjects)

Record nonstudy vaccinations as described in Section 5.8.4.

Collect a blood sample of approximately 25 mL for antibody assessment.

Collect a blood sample of approximately 50 mL for cellular assays (from consenting 
PBMC subjects at PBMC collection sites only).

Record AEs as described in Section 8.

Schedule an appointment for the subject to return for the next study visit.

Complete the source documents.

The investigator or an authorized designee completes the CRF.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.
6.3.8. RSV Vaccine Month-0, Month-2 Cohort, Visit 6: 12-Month Follow-up Visit (350
to 378 Days After Visit 3) (applies to all subjects)

Record nonstudy vaccinations as described in Section 5.8.4.

Collect a blood sample of approximately 25 mL for antibody assessment.

Collect a blood sample of approximately 50 mL for cellular assays (from consenting 
PBMC subjects at PBMC collection sites only).

Record AEs as described in Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

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6.4. Unscheduled Reactogenicity Visits Following Vaccination
If the subject reports 1 or more of the following, a contact must occur as soon as possible 
between the subject and the investigator, or a medically qualified member of the study site 
staff, to assess if an unscheduled visit is required.

redness at the injection site measuring on the left arm >20 measuring device units 
(>10.0 cm).

swelling at the injection site measuring on the left arm >20 measuring device units 
(>10.0 cm).

any blackening of the skin (necrosis) at the injection site on the left arm.

any peeling/scaling of the skin (exfoliative dermatitis) at the injection site on the left arm.

fever 102.1F (39.0C).

severe injection site pain on the left arm.

severe fatigue.

severe headache.

severe nausea.

severe vomiting.

severe diarrhea.

severe muscle pain.

severe joint pain.
A site visit must be scheduled as soon as possible to assess the extent of the reaction unless:

The subject is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the contact, or

The subject recorded an incorrect value in the e-diary (confirmation of an e-diary data 
entry error).
This contact will be recorded in the CRF and in the subject’s source documentation.
If the subject is unable to attend the unscheduled visit, any ongoing reactions must be 
assessed at the next scheduled visit.

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The reaction(s) 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, who will:

Measure oral temperature.

Measure the subject’s pulse rate.

Measure the subject’s blood pressure (sitting).

Measure minimum and maximum diameters of redness on the left arm (if present).

Measure minimum and maximum diameters of swelling on the left arm (if present).

Assess any blackening of the skin (necrosis) at the injection site on the left arm.

Assess any peeling/scaling of the skin (exfoliative dermatitis) at the injection site on the 
left arm.

Assess any injection site pain on the left arm that is present in accordance with the 
reactogenicity grading scale provided in Section 7.3.2.

Assess for lymphadenopathy associated with any local reaction.

Assess any systemic events (fatigue, headache, nausea, vomiting, diarrhea, muscle pain, 
or joint pain) that are present in accordance with the reactogenicity grading scale 
provided in Section 7.3.4.

Ask the subject if he/she attended an emergency room visit or was hospitalized.

For severe pain at the injection site on the left arm associated with an emergency room 
visit or hospitalization, severe systemic events, associated with an emergency room visit 
or hospitalization, or any necrosis or exfoliative dermatitis, the investigator must assess 
these events in accordance with the severity AE grading scale provided in Section 8 for 
documentation on the AE CRF.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
Subjects will be instructed to contact the site to report any significant illness, medically 
attended event, or hospitalization that occurs during the study period.

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6.5. Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the 
Withdrawal From the Study Due to Adverse Events section) or behavioral reasons, or the 
inability of the subject to comply with the protocol-required schedule of study visits or 
procedures at a given study site.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record.  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject return for a final visit, if applicable, 
and follow up with the subject regarding any unresolved AEs.
If the subject withdraws from the study, and also withdraws consent 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.
Subjects who withdraw after randomization will not be replaced.
Lost to follow-up:
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status.  Lost to follow-up is defined by the inability to reach the subject after a minimum of 
2 documented phone calls, faxes, or emails as well as lack of response by the subject to 
1 registered mail letter.  All attempts should be documented in the subject’s medical records.  
If it is determined that the subject has died, the site will use locally permissible methods to 
obtain the date and cause of death.  The site staff and representative may consult publicly 
available sources, such as public health registries and databases, in order to obtain updated 
contact information.  If, after all attempts, the subject remains lost to follow-up, then the 
last-known-alive date as determined by the investigator should be reported and documented 
in the subject’s medical records.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases, the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely manner.

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For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
7.1. Biological Samples
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 subject’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 
may be stored for up to 20 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 safety 
profile and/or 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.  
 
 
 
 
 
The subject may request that his or 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.
7.2. Immunogenicity
Blood samples will be collected as detailed in Section 6:
Primary Study Cohort - Stage 1: The total volume of blood collected from each subject 
will be approximately 225 mL over the course of the 1-year study. An additional 
approximately 300 mL will be collected from consenting PBMC subjects for the exploratory 
cellular analysis endpoints. The total volume of blood collected from subjects at these sites
will be approximately 525 mL over the 1-year study period.
Primary Study Cohort - Stage 2: The additional blood volume collected from each subject 
participating in the revaccination stage is approximately 125 mL. 
At PBMC collection sites, approximately 250 mL will be collected from consenting PBMC 
subjects for the exploratory cellular analysis endpoints. The total volume of blood collected 
from subjects at these sites will be approximately 375 mL during Stage 2.
RSV Vaccine Month-0, Month-2 Cohort: The total volume of blood collected from each 
subject will be approximately 150 mL over the course of the 1-year study.  
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At PBMC collection sites, approximately 450 mL will be collected from consenting PBMC 
subjects for the exploratory cellular analysis endpoints.  The total volume of blood collected 
from subjects at these sites will be approximately 600 mL over the 1-year study period.
Whole blood will be taken for isolation of PBMCs for further research into the immune 
response (eg, B cells, plasmablasts, T cells).
Sample collection, processing, storage, and shipping information can be found in the study 
reference manual (SRM) or equivalent manual. All assays will be performed at Pfizer 
Vaccine Research & Development located at 401 North Middletown Road, Pearl River, NY 
10965 and/or at a facility designated by Pfizer.
7.2.1. RSV and Influenza Vaccine Antibody Testing
Sera collected will be assayed for RSV A– and RSV B–neutralizing antibody levels, 
anti-RSV prefusion F IgG levels, and immunoglobulin levels against nonvaccine RSV 
antigens.  RSV A– and RSV B–neutralizing antibody levels will be determined for each 
blood sample and reported as the neutralizing titer.  IgG levels will be determined against 
both RSV A and RSV B vaccine prefusion F antigens in a direct-binding Luminex 
immunoassay (dLIA) and reported as an anti-RSV prefusion F IgG antibody titer.  
Immunoglobulin levels against nonvaccine RSV antigens will also be tested by dLIA.
Hemagglutination inhibition antibody titers will be measured by the standard 
hemagglutination inhibition assay (HAI) for the influenza vaccine strains contained in the 
vaccine. H3N2-neutralizing antibody titers will also be investigated. Testing will be 
performed by a facility designated by Pfizer.
7.2.2. Exploratory Assays, Immunogenicity Assessments, and Assay Development
PBMCs isolated from whole blood will be used for evaluation of cellular immune responses 
to the RSV vaccine formulations.  Exploratory analyses may include characterization of 
B-cell, plasmablast, and T-cell immune responses, and repertoire analyses.
A subset of subjects will be included in the whole blood collection procedural requirements 
for the exploratory cellular analysis endpoints for this study.  The subset will be determined 
at the site level; specifically, those sites that have access to the appropriate 
specimen-processing laboratories will provide all subjects for the subset.  It is anticipated that 
the subjects from the selected sites will constitute approximately 1/3 of the total number of 
randomized subjects.
Sera and plasma remaining after completion of the planned immunologic assays from blood 
draws taken throughout the study may be used for additional vaccine and infectious 
disease-related research, including exploratory immunologic assays for further 
characterization of the vaccine response.
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7.3. Safety Parameters
Safety parameters will be assessed as described in the Schedule of Activities and below.
A medical history and physical examination will be performed on all subjects, to establish a 
baseline.  Significant medical history and observations from the physical examination will be 
documented in the CRF.
The safety parameters include e-diary reports of local reactions and systemic events that 
occur in the 14 days after investigational product administration at each vaccination visit.  
These prospectively collected occurrences of local reactions and systemic events are graded 
as described in Section 7.3.1.
In the Primary Study Cohort - Stage 1, the first 4 subjects vaccinated in the study must be 
observed by blinded site staff for any acute reactions for at least 4 hours after vaccination. 
Vaccination of subjects will be limited to a maximum of 6 subjects per day during the first 
week of enrollment (up to 30 vaccinated subjects in total) to maintain safety oversight.
For subjects enrolled, thereafter, irrespective of study cohort, blinded site staff must observe 
subjects for any acute reactions for at least 30 minutes after investigational product 
administration. Acute reactions after investigational product administration will be assessed 
and documented.
In addition, AEs, medically attended AEs (MAEs), AEs of specific interest, and SAEs are 
collected, recorded, and reported as defined in Section 8. An MAE is defined as a nonserious 
AE that results in an evaluation at a medical facility.
7.3.1. Subject Electronic Diary
The subject will be asked to monitor and record local reactions (left arm), systemic events, 
fever, and antipyretics/pain medication used to treat symptoms, each evening for 14 days 
following each vaccination visit (Day 1 through Day 14, where Day 1 is the day of 
vaccination). The e-diary allows recording of these assessments only within a fixed time 
window, thus providing the accurate representation of the subject’s experience at that time.  
Data on local reactions, systemic events, and antipyretics/pain medication used to treat 
symptoms recorded in the e-diary will be transferred electronically to the e-diary vendor, 
where they will be available for review by investigators, their qualified designees, and 
sponsor staff at all times via an internet-based portal.  At intervals agreed to by the vendor 
and Pfizer, these data will be transferred electronically to Pfizer for analysis and reporting.  
These data do not need to be recorded by the investigator in the CRF.  However, if a subject 
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.
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Investigators (or appropriately qualified designee) are required to review the e-diary data 
online to evaluate subject compliance and as part of the ongoing safety review (see Stopping 
Rules in Section 7.4).
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.
7.3.2. Grading Scales
The grading scales used in this study to assess local reactions and systemic events (including 
fever) described in Tables 4 through 6 below are derived from the Food and Drug 
Administration (FDA) Center for Biologics Evaluation and Research (CBER) guidelines on 
toxicity grading scales for healthy adult volunteers enrolled in preventive vaccine clinical 
trials.11
7.3.3. Local Reactions
Following each vaccination visit (Day 1 through Day 14, where Day 1 is the day of 
vaccination), subjects will be asked to assess redness, swelling, and pain at the injection site
(left arm) and to record the symptoms in the e-diary in the evening.  Subjects will also record 
any peeling/scaling (exfoliative dermatitis) or blackening of the skin (necrosis), at the 
injection site on the left arm.
Redness and swelling will be measured and recorded in measuring device units 
(range: 1 to 20, and 21) and then categorized during analysis as mild, moderate, or severe
based on the grading scale in Table 7 below.  Measuring device units can be converted to 
centimeters according to the following scale: 1 measuring device unit = 0.5 cm.
A subject with severe redness, swelling, or pain or any peeling/scaling (exfoliative 
dermatitis) or blackening of the skin (necrosis) at the injection site on the left arm will be 
prompted to contact the investigator to perform an unscheduled visit to assess the reaction. If 
the subject does not call the investigator, the site should call the subject.
Only an investigator is able to classify a subject’s local reaction as Grade 4, after clinical 
evaluation of the subject 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 subject.  If a subject experiences a Grade 4 local reaction, the investigator 
must immediately notify the sponsor. Grade 4 reactions will be collected as an AE on the 
CRF. The event will be graded using the AE severity grading scale (Section 8.3).
Site staff will educate the subject regarding signs and symptoms that would prompt site 
contact. The procedure for notification of the sponsor is provided in the study 
documentation.
If a local reaction persists beyond the end of the e-diary period, the subject 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 subject’s source notes and CRF.

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Table 7.
Grading Scale for Local Reactions
Mild 
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4 a
Redness
2.5 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
2.5 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.
Grade 4 assessment should be made by the investigator using the AE severity grading scale. The 
assessment will be collected on the AE case report form.
7.3.4. Systemic Events
Following each vaccination visit (Day 1 through Day 14, where Day 1 is the day of 
vaccination), subjects will be asked to assess fatigue, headache, vomiting, nausea, diarrhea, 
muscle pain, and joint pain and to record the symptoms in the e-diary in the evening.  The 
symptoms will be assessed by the subject according to the grading scale in Table 8 below. 
Subjects will also be instructed to contact site staff if they experience any Grade 3 prompted 
systemic event or if they visit the emergency room visit or are hospitalized for severe fatigue, 
headache, vomiting, nausea, diarrhea, muscle pain, or joint pain) within 14 days after each 
vaccination visit.  Study staff may also contact the subject to obtain additional information on 
entered into the e-diary.
Only an investigator is able to classify a subject’s systemic event as Grade 4, after clinical 
evaluation of the subject or documentation from another medically qualified source 
(eg, emergency room or hospital record) or contact with the subject.  If a subject experiences 
a Grade 4 systemic event, the investigator must immediately notify the sponsor. The 
procedure for notification of the sponsor is provided in the study documentation. Grade 4 
reactions will be collected as an AE on the CRF. The event will be graded using the AE 
severity grading scale (Section 8.3).
Further, if a systemic event persists beyond the end of the e-diary period, the subject 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 CRF.
Table 8.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4 a
Fatigue
(= tiredness in 
diaries)
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room 
visit or 
hospitalization for 
severe fatigue 

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Table 8.
Grading Scale for Systemic Events
Mild
Grade 1
Moderate
Grade 2
Severe
Grade 3
Grade 4 a
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.
Grade 4 assessment should be made by the investigator using the AE severity grading scale. The 
assessment will be collected on the AE case report form.
7.3.5. Fever
A digital thermometer will be given to the subject with instructions on how to measure oral 
temperature at home.  Temperature will be collected in the evening daily for 14 days 
following each vaccination visit (Day 1 through Day 14, where Day 1 is the day of 
vaccination) and at any time during the 14 days following vaccination that fever is suspected.  
Fever is defined as an oral temperature of 100.4°F (38.0°C).  The highest temperature for 
each day will be recorded in the e-diary.
In the event of a fever on Day 14, temperature will be measured daily until fever has resolved 
(1 day of temperature less than 100.4°F [38.0°C]) in order to collect a stop date in the CRF.
A subject with a fever 102.1F (39.0C) will be prompted to contact the investigator to 
assess the fever and perform an unscheduled visit as appropriate.
Temperature will be measured and recorded to 1 decimal place and then grouped into ranges 
for the analysis according to Table 9 below:

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Table 9.
Ranges for Fever
Fever
38.0C to 38.4C
100.4F to 101.1F
38.5C to 38.9C
101.2F to 102.0F
39.0C to 40.0C
102.1F to 104.0F
>40.0C
>104.0F
7.3.6. Use of Antipyretic/Pain Medication
For 14 days following each vaccination visit (Day 1 through Day 14, where Day 1 is the day 
of vaccination), the subject will be asked to record the use of antipyretic and/or pain 
medication in the e-diary.
7.4. Stopping Rules
AE data and e-diary reactogenicity data will be monitored on an ongoing basis by the 
investigator (or medically qualified designee) and sponsor in order to promptly identify and 
flag any event that potentially contributes to a stopping rule.
If it is suspected that a stopping rule has been met based on blinded safety assessment, the 
sponsor’s designated unblinded personnel will decide whether a stopping rule has been met 
based on unblinded randomization information.
In the event that the unblinded sponsor personnel confirm that a stopping rule is met, the 
following actions will commence:
The IRC will review all appropriate data.
The stopping rule will PAUSE all randomization and RSV vaccination.
The E-DMC will be informed.
For all subjects vaccinated, all other routine study conduct activities, including ongoing 
data entry, reporting of AEs, subject e-diary completion, blood sample collection, and 
subject follow-up, will continue during the pause.
A stopping rule is met if any of the following rules occur after administration of 
investigational RSV vaccine. E-diary data confirmed by the investigator as being entered by 
the subject in error will not contribute toward a stopping rule.
All formulations, with Al(OH)3, with CpG/Al(OH)3, or with sterile water, at a given dose 
will be evaluated for contribution to stopping rules together.  However, it is possible that the 
recommendations may include halting or continuing randomization with any of the 
formulations at a given dose.

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Stopping Rule Criteria for All Formulations:
1. If any RSV-vaccinated subject develops an SAE that is assessed as possibly related, or 
for which there is no alternative, plausible, attributable cause.
2. If any RSV-vaccinated subject develops a Grade 4 local reaction or systemic event within 
14 days after vaccination that is assessed as possibly related by the investigator, or for 
which there is no alternative, plausible, attributable cause.
3. If any RSV-vaccinated subject develops a fever >104.0°F (40°C) for at least 1 daily 
measurement within 14 days after vaccination that is assessed as possibly related by the 
investigator, or for which there is no alternative, plausible, attributable cause.
4. If 3 RSV-vaccinated subjects (at any dose level) report the same or similar severe (Grade 
3) AE within 14 days after vaccination, assessed as possibly related by the investigator, 
or for which there is no alternative, plausible, attributable cause.
7.4.1. Randomization and Vaccination After a Stopping Rule Is Met
Once the IRC has reviewed the safety data and has provided guidance, a notification will be 
sent from the sponsor to the sites with guidance on how to proceed.
8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; 
(2) nonserious AEs; and (3) exposure to the investigational product under study during 
pregnancy or breastfeeding, and occupational exposure.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the investigational 
product under study during 
pregnancy or breastfeeding, and 
occupational exposure
All (regardless of whether associated 
with an AE), except occupational 
exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure (regardless of 
whether associated with an AE)
All observed or volunteered events regardless of vaccine group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.

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Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this 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 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety.  Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
To be able to identify and clarify stopping rules, when the investigator becomes aware of a 
related SAE or a severe related AE, the investigator must immediately contact the Pfizer 
study physician. This procedure does not replace any of the standard AE recording and 
reporting requirements as described in the following sections.

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8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously
reported by the study subject.  In addition, each study subject will be questioned about the 
occurrence of AEs in a nonleading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF.
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product), as follows:

SAEs: From informed consent until study completion. 

AEs:

Primary Study Cohort - Stage 1: Informed consent until Visit 2 (1 month after 
Vaccination 1). Thereafter MAEs will be collected.

Primary Study Cohort - Stage 2: Visit 5 until Visit 6 (1 month after Vaccination 
2). Thereafter MAEs will be collected.

RSV Vaccine Month-0, Month-2 Cohort: Informed consent until Visit 4 (1 month 
after Vaccination 2). Thereafter MAEs will be collected.

Occurrences of AEs of specific interest (refer to Table 10) will be recorded from 
administration of the investigational product until the subject completes the study,
regardless of causality.

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
Any AE occurring up to 48 hours after the blood draws at all study visits must be 
recorded and reported in the CRF.

All AEs should be followed for resolution throughout the study. Stop dates are to be 
recorded in the CRF and source documents.
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally, the 
facts (evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records.
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 CT SAE Report Form and in 
accordance with the SAE reporting requirements.

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8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study subject administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to: 

Abnormal test findings;

Clinically significant signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease:

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

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
Medication error;

Occupational exposure.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met:

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result 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; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.

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Examples of such events are 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.
Medical device complaints may meet the SAE reporting requirement criteria (see the Medical 
Device Complaint Reporting Requirements section).  An incident is any malfunction (ie, the 
failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a subject, or user, or of 
other persons, or to a serious deterioration in their state of health.
A serious injury that can cause a serious deterioration in state of health can include:

A life-threatening illness, even if temporary in nature;

A permanent impairment of a body function or permanent damage to a body 
structure; 

A condition necessitating medical or surgical intervention to prevent the above 
2 bulleted items;
Examples: clinically relevant increase in the duration of a surgical procedure; a 
condition that requires hospitalization or significant prolongation of existing 
hospitalization;

Any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic 
device test results when used within the manufacturer’s instructions for use;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

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
Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
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 subject's usual function.
2
MODERATE
Interferes to some extent with subject's usual function.
3
SEVERE
Interferes significantly with subject's usual function.
4
LIFE-
THREATENING
Life-threatening consequences; urgent intervention indicated.

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Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections and will be handled as SAEs in 
the safety database.
8.4.2. Adverse Events of Specific Interest
AEs of specific interest for safety monitoring include the occurrence of autoimmune 
disorders listed in Table 10. These events will be documented as AEs on the CRF and 
reported as SAEs if the event meets the seriousness criteria (Section 8.2.3). Notification of 
AEs of specific interest to the Pfizer clinical team and completion of the AE CRF page 
should be done within 24 hours of investigator awareness.
Table 10.
Autoimmune Diseases/Disorders
Gastrointestinal disorders 

Celiac disease

Crohn disease

Ulcerative colitis

Ulcerative proctitis
Liver disorders

Autoimmune cholangitis

Autoimmune hepatitis

Primary biliary cirrhosis

Primary sclerosing cholangitis
Metabolic disorders 

Addison disease

Autoimmune thyroiditis (including Hashimoto thyroiditis)

Diabetes mellitus type 1

Graves or Basedow disease

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Table 10.
Autoimmune Diseases/Disorders
Musculoskeletal disorders 
Antisynthetase syndrome

Dermatomyositis

Juvenile chronic arthritis (including Still disease)

Mixed connective tissue disorder

Polymyalgia rheumatica

Polymyositis

Psoriatic arthropathy

Relapsing polychondritis

Rheumatoid arthritis

Scleroderma, including diffuse systemic form and CREST syndrome

Spondyloarthritis, including anklylosing spondylitis, reactive arthritis 
(Reiter syndrome), and undifferentiated spondyloarthritis

Systemic lupus erythematosus

Systemic sclerosis
Neuroinflammatory 
disorders 

Acute disseminated encephalomyelitis, including site-specific variants,
eg, noninfectious encephalitis, encephalomyelitis, myelitis, radiculomyelitis

Cranial nerve disorders, including paralyses/paresis (eg, Bell palsy)

Guillain-Barré syndrome, including Miller Fisher syndrome and other variants 

Immune-mediated peripheral neuropathies and plexopathies, including chronic 
inflammatory demyelinating polyneuropathy, multifocal motor neuropathy,
and polyneuropathies associated with monoclonal gammopathy

Multiple sclerosis

Narcolepsy

Optic neuritis

Transverse myelitis

Myasthenia gravis, including Eaton-Lambert syndrome
Skin disorders

Alopecia areata

Autoimmune bullous skin diseases, including pemphigoid, pemphigus, and 
dermatitis herpetiformis 

Cutaneous lupus erythematosus

Erythema nodosum

Morphea

Lichen planus

Psoriasis

Sweet syndrome

Vitiligo
Vasculitides

Large-vessel vasculitis, including giant cell arteritis such as Takayasu arteritis 
and temporal arteritis 

Medium-sized and/or small-vessel vasculitis, including polyarteritis nodosa, 
Kawasaki disease, microscopic polyangiitis, Wegener granulomatosis
(granulomatosis with polyangiitis), Churg-Strauss syndrome (allergic 
granulomatous angiitis), Buerger disease (thromboangiitis obliterans), 
necrotizing vasculitis and antineutrophil cytoplasmic antibody 
(ANCA)-positive vasculitis (type unspecified), Henoch-Schönlein purpura, 
Behçet syndrome, and leukocytoclastic vasculitis

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Table 10.
Autoimmune Diseases/Disorders
Others

Antiphospholipid syndrome

Autoimmune hemolytic anemia

Autoimmune glomerulonephritis, including IgA nephropathy, 
glomerulonephritis rapidly progressive, membranous glomerulonephritis, 
membranoproliferative glomerulonephritis, and mesangial proliferative 
glomerulonephritis

Autoimmune myocarditis/cardiomyopathy

Autoimmune thrombocytopenia

Goodpasture syndrome

Idiopathic pulmonary fibrosis

Pernicious anemia

Raynaud phenomenon

Sarcoidosis

Sjögren syndrome

Stevens-Johnson syndrome

Uveitis
Abbreviations: CREST = calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and 
telangiectasia; IgA = immunoglobulin A.
8.4.3. 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 subjects, transaminase elevations are a harbinger of a more 
serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury
(DILI).
Subjects who experience a transaminase elevation above 3 times the upper limit of normal 
(× ULN) should be monitored more frequently to determine if they are an “adaptor” or are 
“susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a subject 
presents with clinical signs/symptoms, such LFT results should be managed and followed as 
described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 

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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 subject’s 
individual baseline values and underlying conditions.  Subjects 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:

Subjects 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 subjects with baseline AST OR ALT OR TBili values above the ULN, the following 
threshold values are used in the definition mentioned above, as needed, depending on 
which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT values 
>2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The subject 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, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase, and acetaminophen drug and/or protein adduct levels.  
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) may be warranted.

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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.
8.4.4. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.4.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an EDP occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed during 
his partner’s pregnancy.
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, regardless of 
whether an SAE has occurred.  In addition, the investigator must submit information 
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a subject 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) to Pfizer Safety using the EDP supplemental form.  This must be done irrespective 
of whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 

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completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
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 subject with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 
subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.4.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure-during-breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.4.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 

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SAE.  Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.4.5. Medication Errors
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 24 
Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
8.4.5.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength.
Medication errors include:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the participating subject.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
Other examples include, but are not limited to:

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

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
The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use.
8.5. Medical Device Complaint Reporting Requirements
All medical device complaints, regardless of whether the medical device complaint is 
associated with an AE, will be reported by an unblinded member of the site staff to the 
assigned study team member as described in the Investigational Product Complaint section of 
the IP manual. This includes potential incidents or malfunctions associated with the use of a 
medical device product.  An incident or malfunction is an event that might have led to death 
or serious deterioration in health, or if it occurred again might lead to death or serious 
deterioration in health.
Pfizer is to be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event.
Medical device complaints that are not associated with an SAE, ie, for marketed/registered 
products, should be forwarded to Pfizer Global Manufacturing. For medical device products 
not yet approved/registered anywhere in the world, product complaints should be forwarded
to Pharmaceutical Sciences.
9. DATA ANALYSIS/STATISTICAL METHODS
Methodology for summary and statistical analyses of the data collected in this study is 
outlined here and additional details will be documented in the statistical analysis plan (SAP). 
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.
All analyses for both immunogenicity and safety data will be descriptive in nature.
9.1. Sample Size Determination
Sample size calculation is not based on any formal statistical hypothesis testing. Two (2)
study cohorts will be examined. Approximately 250 subjects were enrolled in the Primary 
Study Cohort - Stage 1, and approximately 62 subjects will be enrolled in the RSV Vaccine 
Month-0, Month-2 Cohort. Refer to Table 4 for a detailed description of the number of 
subjects per group. Sample size for the Primary Study Cohort - Stage 2 is dependent upon 
the number of invited subjects who consent to revaccination at Month 12.
For safety outcomes, Table 11 shows the probability of observing at least 1 AE for a given 
true event rate of a particular AE, for various sample sizes. For example, if the true AE rate 
is 5%, with 31 subjects in in a vaccine group, there is 80% probability of observing at least 
1 AE.

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Table 11.
Probability of Observing at Least 1 AE by Assumed True Event Rates With 
Different Sample Sizes
Assumed True Event 
Rate of an AE
N=31
N=62
N=93
N=217
0.5%
0.14
0.27
0.37
0.66
1%
0.27
0.46
0.61
0.89
2%
0.47
0.71
0.85
0.99
3%
0.61
0.85
0.94
>0.99
5%
0.80
0.96
0.99
>0.99
Note: In this study, 31 subjects are planned to be vaccinated with a specific RSV formulation at each dose 
level.  62 subjects are planned to be vaccinated with a specific dose level of adjuvanted RSV vaccine, 
93 subjects are the maximum number of subjects to be vaccinated at a dose level from all 3 formulations, 
and 217 subjects are the combined subjects from all formulations and dose levels of RSV vaccine.
9.2. Immunogenicity Analysis
Immunogenicity results will be summarized by vaccine group and by study cohort.
9.2.1. Immunogenicity Analysis Populations
For the immunogenicity analyses, 2 analysis populations will be defined for each study 
cohort: Primary Study Cohort - Stage 1, Primary Study Cohort - Stage 2, and the RSV 
Vaccine Month-0, Month-2 Cohort.
9.2.1.1. Primary Study Cohort - Stage 1

Evaluable immunogenicity population: In general, the subject must have been eligible 
for the study, have received both SIIV and RSV vaccinations or SIIV and placebo to 
which he or she was randomized, have had blood drawn within the prespecified time 
frames at the 1-month postvaccination follow-up visit, have at least 1 valid and 
determinate assay result for the proposed analysis, and have no other major protocol 
violations.

Modified intent-to-treat (mITT) population: A subject must have been randomized 
and have at least 1 valid and determinate assay result related to the proposed analysis.
9.2.1.2. Primary Study Cohort - Stage 2

Evaluable immunogenicity population: In general, the subject must have been eligible 
for the study, have received vaccination and revaccination (concomitant with SIIV) to 
which the subject was randomized, have had blood drawn within the prespecified time 
frames at the 1-month post-Vaccination 2 follow-up visit, have at least 1 valid and 
determinate assay result for the proposed analysis, and have no other major protocol 
violations.

mITT population: A subject must have been randomized in Stage 1, consented to 
participate in Stage 2 and have at least 1 valid and determinate assay result related to the 
proposed analysis.

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9.2.1.3. RSV Vaccine Month-0, Month-2 Cohort

Evaluable immunogenicity population: In general, the subject must have been eligible 
for the study, have received all vaccinations to which the subject was randomized, have 
had blood drawn within the prespecified time frames at the 1-month post-Vaccination 2 
follow-up visit, have at least 1 valid and determinate assay result for the proposed 
analysis, and have no other major protocol violations.

mITT population: A subject must have been randomized and have at least 1 valid and 
determinate assay result related to the proposed analysis.
The immunogenicity data will be summarized according to the vaccine as received for the 
evaluable immunogenicity population and as randomized for the mITT population. The 
evaluable immunogenicity population will be the primary analysis population for 
immunogenicity results.
9.2.2. Analysis of Immunogenicity Endpoints
Continuous immunogenicity endpoints will be logarithmically transformed for analysis. 
Geometric mean titers (GMTs) and associated 2-sided 95% confidence intervals (CIs) will be 
calculated at each available time point for each vaccine group and cohort. CIs will be 
calculated by back transformation of the CIs for the mean of the logarithmically transformed 
assay results computed using Student’s t distribution.
Geometric mean fold rises (GMFRs) and associated 2-sided 95% CIs will be provided for 
RSV A– and RSV B–neutralizing antibody titers from before vaccination to each available 
time point after vaccination for each vaccine group and cohort. The GMFR will be 
calculated as the mean difference of individual subject logarithmically transformed antibody 
levels (postvaccination minus prevaccination) and back transformed to the original units.
Two (2)-sided 95% CIs are also computed by back transformation of the CIs using 1-sample 
Student’s t distribution for the mean difference of measures on the logarithmically 
transformed assay results.
To assess whether concomitant administration of RSV and influenza vaccines interferes with 
the immune response to SIIV, geometric mean ratios (GMRs) and associated 2-sided 95% 
CIs will be calculated for HAI strains in SIIV by comparing sera drawn from subjects 
vaccinated with SIIV concomitantly with, for example, RSV vaccine 60 g + CpG/Al(OH)3
to sera drawn from subjects vaccinated with SIIV alone at 1 month after vaccination. This 
analysis will also be done for the other formulations and dose levels of RSV vaccine. The 
GMR will be calculated as the group mean difference of logarithmically transformed 
antibody levels and back transformed to the original units. Two (2)-sided 95% CIs are also 
computed by back transformation of the CIs using 2-sample Student’s t distribution for the 
mean difference of measures on the logarithmically transformed assay results.

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Seroprotection in HAI titers is defined as the percentage of subjects achieving a HAI 
antibody titer 1:40. The percentage of subjects achieving a seroprotection at 1 month after 
vaccination will be computed for each virus strain contained in SIIV separately.
Seroconversion in HAI titers is defined as the percentage of subjects with either a 
prevaccination HAI titer <1:10 and a postvaccination HAI titer 1:40 or a prevaccination 
HAI titer 1:10 and a minimum 4-fold rise in postvaccination HAI antibody titer with respect 
to the prevaccination titer for influenza virus strains.
All binary endpoints, including seroprotection and seroconversion rates after SIIV as well as 
those defined in Section 2, will be descriptively summarized with 2-sided 95% CIs for each 
vaccine group by the Clopper-Pearson exact method.
In addition, for seroprotection and seroconversion rates, exact, unconditional, 2-sided 95% 
CIs for the difference in percentages will be calculated between subjects immunized with 
SIIV concomitantly with each formulation and dose level of RSV vaccine and subjects 
immunized with SIIV and placebo at 1 month after vaccination. The CIs will be computed 
using the procedure of Chan and Zhang, using the standardized test statistic and 
gamma=0.000001.
Reverse cumulative distribution curves (RCDCs) for RSV-neutralizing antibody titers for a 
combination of prespecified time points and vaccine groups will be generated.
Detailed analyses of all the immunogenicity endpoints including graphical displays will be 
described in the SAP.
9.3. Safety Analysis
Safety and tolerability results will be summarized by vaccine group and by study cohort.
All subjects receiving at least 1 dose of the investigational products will be included in the 
safety population. For the safety analyses, subjects will be analyzed according to the 
investigational product received.
The safety endpoints are primary endpoints in the study and their analyses are based on the 
safety population.
The safety analyses are descriptive evaluations of local reactions, systemic events, AEs, 
MAEs, AEs of specific interest, and SAEs. AEs will be categorized according to the Medical 
Dictionary for Regulatory Activities (MedDRA).
Descriptive summary statistics (eg, counts and percentages) will be provided for AEs and 
e-diary events, with 2-sided 95% exact CIs as appropriate.
The 3-tier approach will be used for the summary of AEs. Detailed definitions for each tier 
will be described in the SAP.

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9.4. Analysis Timing
Three interim analyses will be conducted before the final analysis at the completion of the 
study:

Primary Study Cohort - Stage 1
An analysis will be conducted when 1-month postvaccination immunogenicity data from all 
subjects in the Primary Study Cohort - Stage 1 are available. All available safety, 
tolerability, and immunogenicity data from subjects will be included in the analysis.

Primary Study Cohort - Stage 2
An analysis will be conducted when 1-month post-Vaccination 2 immunogenicity data from 
all subjects in the Primary Study Cohort - Stage 2 are available. All available safety, 
tolerability, and immunogenicity data will be included in the analysis.

RSV Vaccine Month-0, Month-2 Cohort
An analysis will be conducted when 1-month post-Vaccination 2 immunogenicity data from 
all subjects in this cohort are available. All available safety, tolerability, and immunogenicity 
data will be included in the analysis.
The results of these analyses will be used to select the most appropriate dose(s),
formulation(s), and dosing schedule of the RSV vaccine for use in further studies in older 
adults.
Additional analysis may be conducted before the final analysis to support other internal 
program level decisions as needed.
Safety data will be summarized on an ongoing basis. No multiplicity adjustments will be 
applied for these analyses.
The final analysis will be performed after all the subjects complete the study and when all of 
the data are available.
9.5. Data Monitoring Committee(s)
This study will use an unblinded IRC and an E-DMC. The IRC will consist of at least 
3 qualified Pfizer experts, including at least a physician and a statistician, who are not 
directly involved in the study conduct.
The IRC will convene to review data on an ad hoc basis (eg, stopping rules are met,
occurrence of suspected unexpected serious adverse reactions (SUSARs), unexpected safety 
or study conduct concerns). The committee will also review the results of any planned 
analysis when the required data are available.

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The E-DMC will review study data according to the charter and any time a stopping rule is
met, or other safety concern is identified.
The E-DMC will be responsible for ongoing monitoring of the safety of subjects in the study
according to the charter. The recommendations made by the E-DMC to alter the conduct of 
the study will be forwarded to Pfizer for final decisions. Pfizer will forward such decisions, 
which may include summaries of aggregate analyses of endpoint events and of safety data 
that are not endpoints, to regulatory authorities, as appropriate.
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and GCPs are being followed.  The monitors may review source documents to 
confirm that the data recorded on CRFs are accurate.  The investigator and institution will 
allow Pfizer monitors/auditors or its agents and appropriate regulatory authorities direct 
access to source documents to perform this verification.  This verification may also occur 
after study completion.
During study conduct and/or after study completion, the investigator site may be subject to 
review by the institutional review board (IRB)/ethics committee (EC), and/or to quality 
assurance audits performed by Pfizer, or companies working with or on behalf of Pfizer, 
and/or to inspection by appropriate regulatory authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer 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 subject's medical records.
The investigator will promptly provide copies of the inspection findings to Pfizer or its agent.  
Before response submission to the regulatory authorities, the investigator will provide Pfizer 
or its agents with an opportunity to review and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.

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11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.
Any corrections to entries made in the CRFs or source documents must be dated, initialed,
and explained (if necessary) and should not obscure the original entry.
In most cases, the source documents are the hospital or the physician subject chart.  In these 
cases, data collected on the CRFs must match the data in those charts.
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
ICDs, copies of all CRFs, safety reporting forms, source documents, and detailed records of 
treatment disposition, and adequate documentation of relevant correspondence (eg, letters, 
meeting minutes, and telephone call reports).  The records should be retained by the 
investigator according to the ICH guidelines, according to local regulations, or as specified in 
the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer.
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.

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The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, ICDs, and other relevant documents, eg, recruitment advertisements, if 
applicable, from the IRB/EC.  All correspondence with the IRB/EC should be retained in the 
investigator file.  Copies of IRB/EC approvals should be forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects. The investigator
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.
The ICDs and any subject recruitment materials must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements, including applicable privacy laws.
The ICDs used during the informed consent process and any subject recruitment materials 
must be reviewed and approved by Pfizer, approved by the IRB/EC before use, and available 
for inspection.
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation.

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12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in All Participating Countries
End of trial in all participating countries is defined as last subject last visit (LSLV).
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of the 
investigational product at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within a reasonable time frame.  As directed by Pfizer, all study materials 
must be collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  
US Basic Results are submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.

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PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication. However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.

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For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.

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16. REFERENCES
1.
Hall CB, Simőes EAF, Anderson LJ. Clinical and epidemiologic features of respiratory 
syncytial virus. In: Anderson LJ, Graham BS, eds. Challenges and Opportunities for 
Respiratory Syncytial Virus Vaccines. Berlin/Heidelberg, Germany: Springer-Verlag 
Berlin Heidelberg; 2013:39-57. Curr Top Microbiol Immunol. 2013;372:39-57. 
doi:10.1007/978-3-642-38919-1_2.
2.
Shi T, McAllister DA, O’Brien KL, et al; for RSV Global Epidemiology Network. 
Global, regional, and national disease burden estimates of acute lower respiratory 
infections due to respiratory syncytial virus in young children in 2015: a systematic 
review and modelling study. Lancet. 2017;390(10098):946-958. doi:10.1016/S0140-
6736(17)30938-8.
3.
Walsh EE, Falsey AR. Respiratory syncytial virus infection in adult populations. Infect
Disord Drug Targets. 2012;12(2):98-102.
4.
Widmer K, Zhu Y, Williams JV, Grifﬁn MR, Edwards KM, Talbot HK. Rates of 
hospitalizations for respiratory syncytial virus, human metapneumovirus, and inﬂuenza 
virus in older adults. J Infect Dis. 2012;206(1):56-62.
5.
American Academy of Pediatrics. Committee on Infectious Diseases and Bronchiolitis 
Guidelines Committee. Policy statement: Updated guidance for palivizumab 
prophylaxis among infants and young children at increased risk of hospitalization for 
respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-420.
6.
Prescott WA Jr, Doloresco F, Brown J, Paladino JA. Cost effectiveness of respiratory 
syncytial virus prophylaxis: a critical and systematic review. Pharmacoeconomics. 
2010;28(4):279-293.
7.
Walsh EE, Peterson DR, Falsey AR. Risk factors for severe respiratory syncytial virus 
infection in elderly persons. J Infect Dis. 2004;189(2):233-238.
8.
Boraschi D, Italiani P. Immunosenescence and vaccine failure in the elderly: strategies 
for improving response. Immunol Lett. 2014;162(1 pt B):346-353.
9.
Scheiermann J, Klinman DM. Clinical evaluation of CpG oligonucleotides as adjuvants 
for vaccines targeting infectious diseases and cancer. Vaccine. 2014;32:6377-6389.
10.
Heplisav-B. Food and Drug Administration Website. 
https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm584752.
htm. Updated 13 Nov 2017; accessed 11 Dec 2017.
11.
Food and Drug Administration, Center for Biologics Evaluation and Research. 
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; September 2007.

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Appendix 1. Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
Al(OH)3
aluminum hydroxide
ALT
alanine aminotransferase
AST
aspartate aminotransferase
CBER
Center for Biologics Evaluation and Research
CI
confidence interval
CK
creatine kinase
COPD
chronic obstructive pulmonary disease
CRA
clinical research associate
CRF
case report form
CSA
clinical study agreement
CT
clinical trial
DILI
drug-induced liver injury
dLIA
direct-binding Luminex immunoassay
EC
ethics committee
e-diary
electronic diary
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FIH
first-in-human
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HAI
hemagglutination inhibition assay
HBV
hepatitis B virus
HCV
hepatitis C virus
HD
high-dose
HIV
human immunodeficiency virus
HRSV
Human respiratory syncytial virus
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IgG
immunoglobulin G
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
IUS
intrauterine system
IWR
interactive Web-based response

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Abbreviation
Term
LFT
liver function test
LRTI
lower respiratory tract infection
LSLV
last subject last visit 
MAE
medically attended adverse event
MedDRA
Medical Dictionary for Regulatory Activities
mITT
modified intent-to-treat
N/A
not applicable
NHP
nonhuman primate
PBMC
peripheral blood mononuclear cell
PCD
primary completion date
PI
principal investigator
PT
prothrombin time
RCDC
reverse cumulative distribution curve
RNA
ribonucleic acid
RSV
respiratory syncytial virus
RSV vaccine
respiratory syncytial virus stabilized prefusion F subunit vaccine
SAE
serious adverse event
SAP
statistical analysis plan
SIIV
seasonal inactivated influenza vaccine
SOP
standard operating procedure
SRSD
single reference safety document
SRM
study reference manual
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
TLR9
Toll-like receptor 9
ULN
upper limit of normal
US
United States

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