A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Modified RNA COVID-19 Vaccine and a Recombinant Influenza Vaccine Administered as a Single Injection in Healthy Adults 50 Years of Age or Older
Phase: PHASE2
Conditions: Influenza, Human, SARS-CoV-2 Infection, COVID-19
Sponsor: Pfizer

PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
Page 1
A PHASE 1/2 RANDOMIZED STUDY TO EVALUATE THE SAFETY, 
TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA COVID-19
VACCINE AND A RECOMBINANT INFLUENZA VACCINE ADMINISTERED AS 
A SINGLE INJECTION IN HEALTHY ADULTS 50 YEARS OF AGE OR OLDER
Study Intervention Number:
PF-08044562
Study Intervention Name:
Combination COVID-19 Vaccine and RIV
US IND Number:
Not Available
EudraCT/EU CT Number:
Not Applicable
ClinicalTrials.gov ID:  
Not Available
Pediatric Investigational Plan Number:
Not Applicable
Protocol Number:
C5681001
Phase:
1/2
Sponsor Legal Address:
Pfizer Inc.
66 Hudson Boulevard East
New York, NY 10001
Brief Title: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 
COVID-19 Vaccine and an Influenza Vaccine Given as a Single Injection in Healthy 
Adults
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.
090177e19f7ceb11\Approved\Approved On: 18-Dec-2023 16:34 (GMT)

PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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Document History
Document 
Version Date
Original protocol
18 December 2023
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................18
1.3. Schedule of Activities .............................................................................................19
2. INTRODUCTION ...............................................................................................................22
2.1. Study Rationale .......................................................................................................22
2.2. Background .............................................................................................................22
2.2.1. Clinical Overview.......................................................................................23
2.2.1.1. BNT162b2.................................................................................23
2.2.1.2. RIV............................................................................................24
2.3. Benefit/Risk Assessment.........................................................................................25
2.3.1. Risk Assessment.........................................................................................26
2.3.2. Benefit Assessment.....................................................................................29
2.3.3. Overall Benefit/Risk Conclusion................................................................29
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ...........................................................29
4. STUDY DESIGN.................................................................................................................31
4.1. Overall Design.........................................................................................................31
4.2. Scientific Rationale for Study Design.....................................................................33
4.2.1. Choice of Contraception/Barrier Requirements .........................................33
4.3. Justification for Dose ..............................................................................................33
4.3.1. Monovalent BNT162b2 (Omi XBB.1.5)....................................................33
4.3.2. RIV .............................................................................................................33
4.3.3. BNT162b2 (Omi XBB.1.5)/RIV ................................................................33
4.4. End of Study Definition ..........................................................................................33
5. STUDY POPULATION......................................................................................................33
5.1. Inclusion Criteria.....................................................................................................34
5.2. Exclusion Criteria....................................................................................................35
5.3. Lifestyle Considerations..........................................................................................37
5.3.1. Contraception..............................................................................................37
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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5.4. Screen Failures ........................................................................................................37
5.5. Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention...........................37
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................38
6.1. Study Intervention(s) Administered........................................................................38
6.1.1. Administration............................................................................................41
6.1.2. Medical Devices .........................................................................................41
6.2. Preparation, Handling, Storage, and Accountability...............................................41
6.2.1. Preparation and Dispensing........................................................................42
6.3. Assignment to Study Intervention...........................................................................43
6.4. Blinding...................................................................................................................43
6.4.1. Blinding of Participants..............................................................................43
6.4.2. Blinding of Site Personnel..........................................................................43
6.4.3. Blinding of the Sponsor..............................................................................43
6.4.4. Breaking the Blind......................................................................................43
6.5. Study Intervention Compliance...............................................................................43
6.6. Dose Modification...................................................................................................43
6.7. Continued Access to Study Intervention After the End of the Study......................44
6.8. Treatment of Overdose............................................................................................44
6.9. Prior and Concomitant Therapy..............................................................................44
6.9.1. Prohibited During the Study.......................................................................44
6.9.2. Permitted During the Study ........................................................................45
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................45
7.1. Discontinuation of Study Intervention ....................................................................45
7.2. Participant Discontinuation/Withdrawal From the Study.......................................46
7.2.1. Withdrawal of Consent...............................................................................47
7.3. Lost to Follow-Up ...................................................................................................47
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................47
8.1. Administrative Procedures ......................................................................................47
8.1.1. Telehealth Visits.........................................................................................48
8.2. Efficacy and/or Immunogenicity Assessments .......................................................48
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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8.2.1. Testing for SARS-CoV-2 and Influenza Exposure ....................................49
8.2.2. Biological Samples.....................................................................................49
8.3. Safety Assessments .................................................................................................49
8.3.1. Physical Examinations................................................................................49
8.3.2. Vital Signs ..................................................................................................50
8.3.3. Clinical Safety Laboratory Assessments ....................................................50
8.3.4. Electronic Diary..........................................................................................50
8.3.4.1. Grading Scales...........................................................................51
8.3.4.2. Local Reactions.........................................................................51
8.3.4.3. Systemic Events ........................................................................52
8.3.4.4. Fever..........................................................................................53
8.3.4.5. Antipyretic Medication .............................................................54
8.3.5. Phase 1 Stopping Rules ..............................................................................54
8.3.6. Pregnancy Testing ......................................................................................55
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................55
8.4.1. Time Period and Frequency for Collecting AE and SAE Information.......56
8.4.1.1. Reporting SAEs to Pfizer Safety...............................................57
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF...................57
8.4.2. Method of Detecting AEs and SAEs ..........................................................57
8.4.3. Follow-Up of AEs and SAEs......................................................................57
8.4.4. Regulatory Reporting Requirements for SAEs...........................................58
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................58
8.4.5.1. Exposure During Pregnancy......................................................58
8.4.5.2. Exposure During Breastfeeding ................................................60
8.4.5.3. Occupational Exposure .............................................................60
8.4.6. Cardiovascular and Death Events...............................................................60
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................61
8.4.8. Adverse Events of Special Interest.............................................................61
8.4.8.1. Lack of Efficacy........................................................................61
8.4.9. Medical Device Deficiencies......................................................................61
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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8.4.9.1. Time Period for Detecting Medical Device Deficiencies .........62
8.4.9.2. Follow-Up of Medical Device Deficiencies..............................62
8.4.9.3. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................62
8.4.10. Vaccination Errors....................................................................................63
8.5. Pharmacokinetics ....................................................................................................64
8.6. Genetics...................................................................................................................64
8.7. Biomarkers ..............................................................................................................64
8.8. Immunogenicity Assessments.................................................................................64
8.9. Health Economics ...................................................................................................64
8.10. Study Procedures...................................................................................................64
8.10.1. Visit 1 – Vaccination (Day 1)...................................................................64
8.10.2. Visit 2 – 4-Week Follow-Up Visit (After Vaccination) – 28 to 35 
Days After Visit 1............................................................................................67
8.10.3. Visit 3 – 6-Month Follow-Up Visit (After Vaccination) – 175 to 
189 Days After Visit 1.....................................................................................67
8.10.4. Unscheduled Visit for a Grade 3 or Suspected Grade 4 Reaction............68
8.10.5. Additional Procedures for Monitoring of Potential Myocarditis or 
Pericarditis .......................................................................................................69
8.10.6. Additional Procedures for Monitoring of Potential Menstrual Cycle 
Disturbances.....................................................................................................69
9. STATISTICAL CONSIDERATIONS ................................................................................70
9.1. Statistical Hypotheses .............................................................................................70
9.1.1. Estimands....................................................................................................70
9.1.2. Multiplicity Adjustment..............................................................................70
9.2. Analysis Sets ...........................................................................................................70
9.3. Statistical Analyses .................................................................................................71
9.3.1. General Considerations...............................................................................71
9.3.1.1. Analysis for Binary Data...........................................................71
9.3.1.2. Analysis for Continuous Data ...................................................72
9.3.2. Primary Endpoint(s)/Estimand(s) Analysis ................................................73
9.3.3. Secondary Endpoint(s)/Estimand(s) Analysis............................................73
9.3.4. Tertiary/Exploratory Endpoint(s) Analysis ................................................74
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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9.4. Interim Analyses .....................................................................................................75
9.4.1. Analysis Timing..........................................................................................75
9.5. Sample Size Determination.....................................................................................75
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................76
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............76
10.1.1. Regulatory and Ethical Considerations ....................................................76
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................76
10.1.2. Financial Disclosure .................................................................................77
10.1.3. Informed Consent Process ........................................................................77
10.1.3.1. Electronic Consent ..................................................................78
10.1.4. Data Protection .........................................................................................78
10.1.5. Committees Structure ...............................................................................79
10.1.5.1. Data Monitoring Committee ...................................................79
10.1.6. Dissemination of Clinical Study Data ......................................................79
10.1.7. Data Quality Assurance ............................................................................80
10.1.8. Source Documents....................................................................................81
10.1.9. Use of Medical Records............................................................................82
10.1.10. Study and Site Start and Closure ............................................................82
10.1.11. Publication Policy...................................................................................83
10.1.12. Sponsor’s Medically Qualified Individual..............................................84
10.2. Appendix 2: Clinical Laboratory Tests .................................................................85
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................86
10.3.1. Definition of AE .......................................................................................86
10.3.2. Definition of an SAE ................................................................................87
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................89
10.3.4. Reporting of SAEs....................................................................................92
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................94
10.4.1. Male Participant Reproductive Inclusion Criteria....................................94
10.4.2. Female Participant Reproductive Inclusion Criteria.................................94
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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10.4.3. Woman of Childbearing Potential ............................................................95
10.4.4. Contraception Methods.............................................................................96
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments .......98
10.6. Appendix 6: Kidney Safety Monitoring Guidelines ...........................................100
10.6.1. Laboratory Assessment of Change in Kidney Function and 
Detection of Kidney Injury............................................................................100
10.6.2. Age-Specific Kidney Function Calculation Recommendations.............100
10.6.2.1. Adults (18 Years and Above)—2021 CKD-EPI 
Equations .........................................................................................100
10.6.3. Kidney Function Calculation Tools........................................................101
10.6.4. Adverse Event Grading for Kidney Safety Laboratory 
Abnormalities.................................................................................................101
10.7. Appendix 7: AEs, ADEs, SAEs, SADEs, USADEs, and Device 
Deficiencies: Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting in Medical Device Studies ...........................................102
10.7.1. Definition of AE and ADE .....................................................................102
10.7.2. Definition of SAE, SADE, and USADE ................................................102
10.7.3. Definition of Device Deficiency.............................................................103
10.7.4. Recording/Reporting and Follow-Up of Medical Device 
Deficiencies....................................................................................................103
10.8. Appendix 8: Abbreviations .................................................................................106
11. REFERENCES ................................................................................................................110
LIST OF TABLES
Table 1.
Schedule of Activities...............................................................................19
Table 2.
Phase 1/2 Vaccine Group Summary.........................................................32
Table 3.
Anatomical Location for Study Intervention Administration...................41
Table 4.
Local Reaction Grading Scale ..................................................................51
Table 5.
Systemic Event Grading Scale..................................................................52
Table 6.
Scale for Fever..........................................................................................53
Table 7.
Probability of Observing at Least 1 AE, by Assumed True Event 
Rate...........................................................................................................75
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and 
Immunogenicity of a Modified RNA COVID-19 Vaccine and a Recombinant Influenza 
Vaccine Administered as a Single Injection in Healthy Adults 50 Years of Age or Older
Brief Title: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 
COVID-19 Vaccine and an Influenza Vaccine Given as a Single Injection in Healthy Adults
Regulatory Agency Identification Number(s):
US IND Number:
Not Available
EudraCT/EU CT Number:
Not Applicable
ClinicalTrials.gov ID:  
Not Available
Pediatric Investigational Plan Number:
Not Applicable
Protocol Number:
C5681001
Phase:
1/2
Rationale:
BNT162b2 (Comirnaty®) is a messenger ribonucleic acid (mRNA)-based vaccine that, as of 
January 2023, has been granted full marketing authorization, conditional marketing 
authorization, emergency use authorization (EUA), or temporary authorization in a total of 
more than 184 countries for the prevention of coronavirus disease 2019 (COVID-19) caused 
by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The original version 
of BNT162b2 encodes the ancestral Wuhan-Hu-1 strain spike glycoprotein. In the 
United States (US), it has been fully licensed for use in individuals 12 years of age and above 
as of 08 July 2022. All versions of the vaccine encode the SARS-CoV-2 spike protein(s) in 
nucleoside-modified messenger ribonucleic acid (modRNA) encapsulated in ribonucleic acid
lipid nanoparticles (RNA-LNPs), which has demonstrated potent immunogenicity, high 
vaccine efficacy (VE), and a favorable safety profile in Phase 1, 2, and 3 human trials, as 
well as in real-world usage. As SARS-CoV-2 continues to circulate, at very high levels, 
Pfizer/BioNTech are investigating RNA-based COVID-19 vaccines to further protect against 
COVID-19 caused by emergent and potentially more antigenically diverse variants. 
BNT162b2 (Omicron [Omi] XBB.1.5), a monovalent vaccine containing mRNA encoding 
the spike protein of the XBB.1.5 variant, will be used in this study as this is the variant 
recommended by the Food and Drug Administration (FDA) beginning in fall 2023.
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
Page 10
Flublok Quadrivalent (referred to as RIV [recombinant influenza virus]) is a recombinant 
influenza vaccine, manufactured in a baculovirus expression vector and insect cell culture 
system, consisting of 4 recombinant influenza hemagglutinin (HA) antigens derived from 
influenza virus type A, subtypes H1 and H3, and 2 type B virus strains (lineages B/Victoria 
and B/Yamagata). HA genes from each of the 4 influenza viruses are inserted into a plasmid 
baculovirus expression vector system (BEVS) and expressed in Spodoptera frugiperda insect 
cells. RIV is indicated for active immunization against influenza disease caused by influenza 
A subtype viruses and type B viruses contained in the vaccine, for use in adults 18 years and 
older.
Annual vaccine programs for SARS-CoV-2 are likely to run concurrently with annual 
influenza campaigns. In practice, BNT162b2 may be given simultaneously with licensed 
influenza vaccines. 
Combining BNT162b2 with RIV in a single injection would increase the likelihood that 
persons seeking either vaccination against SARS-CoV-2 or influenza would opt to protect 
themselves against both pathogens.
This Phase 1/2 study will evaluate the safety, reactogenicity, and immunogenicity of 
BNT162b2 (Omi XBB.1.5) and RIV administered as a mixture in a single injection. 
Objectives, Endpoints, and Estimands:
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
Safety
To describe the safety and 
tolerability of the study 
interventions

Local reactions (pain at the 
injection site, redness, and 
swelling) 

Systemic events (fever, 
fatigue, headache, chills, 
vomiting, diarrhea, new or 
worsened muscle pain, and 
new or worsened joint pain)

Adverse events (AEs)

Serious adverse events (SAEs)
The percentage of participants 
receiving at least 1 dose of study 
intervention reporting:

Local reactions for up to 
7 days following vaccination

Systemic events for up to 
7 days following vaccination

AEs from vaccination 
through 4 weeks after 
vaccination

SAEs from vaccination 
through 6 months after 
vaccination
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (14 April 2023)
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Objectives
Endpoints
Estimands
Immunogenicity
To describe the immune responses 
elicited by BNT162b2 
(Omi XBB.1.5)/RIV, BNT162b2 
(Omi XBB.1.5) + RIV 
coadministered, and BNT162b2 
(Omi XBB.1.5) and RIV 
administered alone (4 weeks after 
vaccination)
SARS-CoV-2 
Omicron (XBB.1.5)–neutralizing 
titers
In participants complying with the 
key protocol criteria 
(evaluable participants):

Geometric mean titers 
(GMTs) before vaccination 
and at 4 weeks after 
vaccination 

Geometric mean fold rise 
(GMFR) from before 
vaccination to 4 weeks after 
vaccination 

Percentage of participants 
with seroresponsea at 4 weeks 
after vaccination
Hemagglutinin inhibition assay 
(HAI) titers against the seasonal 
strains recommended by the World 
Health Organization (WHO) for the 
northern hemisphere 2023-2024 
influenza season
In participants complying with the 
key protocol criteria 
(evaluable participants):

GMTs before vaccination and 
at 4 weeks after vaccination

GMFRs from before 
vaccination to 4 weeks after 
vaccination 

The percentages of 
participants achieving HAI 
seroconversionb at 4 weeks 
after vaccination 

The percentages of 
participants with HAI titers 
≥1:40 before vaccination and 
at 4 weeks after vaccination
a.
Seroresponse is defined as achieving a ≥4-fold rise from baseline (before the study vaccination). If the 
baseline measurement is below the lower limit of quantitation (LLOQ), the postvaccination measure of 
≥4 × LLOQ is considered seroresponse.
b.
Seroconversion is defined as an HAI titer 1:10 prior to vaccination and ≥1:40 at the time point of 
interest, or an HAI titer of ≥1:10 prior to vaccination with a minimum 4-fold rise at the time point of 
interest.
Overall Design:
This is a Phase 1/2 single-blind (site- and sponsor-unblinded) study to evaluate the safety, 
tolerability, and immunogenicity of licensed BNT162b2 (Omi XBB.1.5) and RIV 
administered together as a single injection (referred to as BNT162b2 [Omi XBB.1.5]/RIV) in 
healthy adults 50 years of age or older. 
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
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PFIZER CONFIDENTIAL
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The safety, tolerability, and immunogenicity of BNT162b2 (OmiXBB1.5)/RIV administered 
as a single injection will be compared to BNT162b2 (Omi XBB.1.5) + RIV administered 
simultaneously as 2 separate injections (coadministered), and to BNT162b2 (Omi XBB.1.5) 
or RIV when administered alone. 
Across Phases 1 and 2, approximately 640 participants in total will be randomized with an 
equal randomization ratio (1:1:1:1) to each of the following vaccine groups and stratified by 
age group (50 through 64 years of age and ≥65 years of age):  

Group 1: BNT162b2 (Omi XBB.1.5)/ RIV (as a single injection) administered in the left 
deltoid and placebo administered in the right deltoid

Group 2: BNT162b2 (Omi XBB.1.5) administered in the left deltoid and RIV 
administered in the right deltoid

Group 3: BNT162b2 (Omi XBB.1.5) administered in the left deltoid and placebo 
administered in the right deltoid

Group 4: RIV administered in the left deltoid and placebo administered in the right 
deltoid
During Phase 1, a total of ~20 participants will be enrolled in each vaccine group. Enrollment 
of participants in each vaccine group will be controlled such that ~10 participants 50 through 
64 years of age (sentinel participants, considered Phase 1a) can be vaccinated in each of the 
groups on the first day. This will be monitored by the sponsor, who will inform sites to pause 
enrollment once the target has been reached. Vaccination of the remaining ~40 participants 
(~10 per vaccine group) will commence no sooner than 24 hours after this safety pause. The 
participants vaccinated after the safety pause will be ≥65 years of age (considered Phase 1b). 
Once ~20 participants per vaccine group have been vaccinated in Phase 1, the interactive 
response technology (IRT) system will block any further randomization, pending a review of 
at least 72 hours of safety data for all participants by the internal review committee (IRC). 
The outcome of the safety data review will be documented in a memo, which will be 
circulated to all sites prior to starting enrollment in Phase 2. In Phase 2, approximately 
140 participants 50 years of age or older will be enrolled in each of the 4 vaccine groups. 
Participants will be stratified by age group, 50 through 64 years of age and ≥65 years of age.
Prespecified local reaction and systemic event data will be collected in an electronic diary 
(e-diary) during the 7 days, or longer for ongoing symptoms, after study intervention 
(ie, from Day 1, the day of vaccination, until symptom resolution), as well as any 
medications taken during this period to treat any pain symptoms or fever. 
Blood samples of approximately 20 mL will be collected from all participants for 
immunogenicity assessments prior to vaccination and at 4 weeks and 6 months after 
vaccination.
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PF-08044562 (Combination COVID-19 Vaccine and RIV)
Protocol C5681001
Final Protocol, 18 December 2023
PFIZER CONFIDENTIAL
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Following vaccination, AEs will be collected from informed consent signing through Visit 2
(approximately 4 weeks after vaccination), and SAEs will be collected from informed 
consent signing through Visit 3 (approximately 6 months after vaccination). In addition, AEs 
occurring up to 48 hours after blood draws will also be collected.
Number of Participants:
Phase 1: Approximately 80 participants will be enrolled. 
Phase 2: Approximately 560 participants will be enrolled.
Study Population:
Inclusion Criteria 
Participants must meet the following inclusion criteria to be eligible for enrollment into the 
study:
Age and Sex:
1. Male or female participants aged 50 years or older at Visit 1 (Day 1). 

Refer to the protocol for reproductive criteria for male and female participants.
Disease Characteristics:
Not applicable. 
Other Inclusion Criteria:
2. Participants who are willing and able to comply with all scheduled visits, the 
investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Healthy participants who are determined by medical history, physical examination 
(if required), and clinical judgment of the investigator to be eligible for inclusion in the 
study.

Note: Healthy participants with preexisting stable disease, defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease 
during the 6 weeks before enrollment, can be included. 
4. Capable of giving signed informed consent as described in the protocol, which includes 
compliance with the requirements and restrictions listed in the informed consent 
document (ICD) and in this protocol.
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Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Any medical or psychiatric condition including recent (within the past year) or active 
suicidal ideation/behavior or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the 
study.
2. Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or 
hepatitis B virus (HBV).
3. History of severe adverse reaction associated with any vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study interventions.
4. Participants 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, multiple sclerosis, 
Sjögren’s syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, 
autoimmune thyroiditis, temporal arteritis, psoriasis, and/or insulin-dependent diabetes 
mellitus.
5. Immunocompromised individuals with known or suspected immunodeficiency, 
determined by history and/or laboratory/physical examination.

Note: Individuals who have had a splenectomy or have functional asplenia will be 
considered ineligible. 
6. Current heart disease, uncontrolled hypertension, or a prior history of myocarditis or 
pericarditis.

Note: Hypertension that has been controlled a minimum of 12 weeks, stable coronary 
artery disease, and stable mild valvular disease are not exclusionary.
7. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
8. Women who are pregnant, plan to become pregnant during the study, or are 
breastfeeding.
9. Prior history of ischemic stroke or transient ischemic attack.
10. Prior history of Guillain-Barré syndrome (GBS).
11. Participants with a calculated body mass index (BMI) of ≥35.
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Prior/Concomitant Therapy:
12. Receipt of chronic medications with known systemic immunosuppressant effects 
(including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days 
before enrollment through conclusion of the study.

Note: Systemic corticosteroids are defined as those administered for ≥14 days at a 
dose of ≥20 mg/day of prednisone or equivalent (eg, for cancer or an autoimmune 
disease) or planned receipt throughout the study. Inhaled/nebulized, intra-articular, 
intrabursal, or topical (skin or eyes) corticosteroids are permitted.
13. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies used for 
the treatment or prevention of COVID-19 or those that are considered 
immunosuppressive, from 90 days before study intervention administration, or planned 
receipt throughout the study.
14. Vaccination with any investigational or licensed influenza vaccine within 6 months 
(180 days) before study intervention administration, or ongoing receipt of chronic 
antiviral therapy with activity against influenza.
15. Vaccination with any investigational or licensed COVID-19 vaccine within 6 months 
(180 days) before study intervention administration.
Prior/Concurrent Clinical Study Experience:
16. Participation in other studies involving administration of an investigational product
within 28 days prior to, and/or during, participation in this study.

Note: In addition to administration of investigational products, study interventions 
may include additional procedures, such as collection of biological samples. 
Therefore, participants may not be in another study whereby procedures, such as 
respiratory illness visits, may interfere with compliance with this study’s protocol.
Diagnostic Assessments:
Not applicable.
Other Exclusion Criteria:
17. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members.
18. Deprived of freedom by an administrative or court order, or in an emergency setting, or 
hospitalized involuntarily.
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19. Current alcohol abuse or drug addiction that in the opinion of the investigator might 
interfere with the study conduct or completion.
Study Arms and Duration:
Study Intervention(s)
Intervention 
Name
BNT162b2 (Omi 
XBB.1.5)/RIV
BNT162b2 
(Omi XBB.1.5)
RIV
Normal saline 
placebo
Type
mRNA and
recombinant 
protein vaccine 
mRNA vaccine
Recombinant 
protein vaccine
Placebo
Use
Experimental
Comparator 
Comparator
Placebo for 
blinding
Investigational 
Medicinal Product 
(IMP) or 
Noninvestigational 
Medicinal Product 
(NIMP)/Auxiliary 
Medicinal Product 
(AxMP)
IMP
IMP
IMP
IMP
Dose Formulation
Suspension for 
injection and 
recombinant 
Suspension for 
injection
Solution for 
injection
Normal saline 
(0.9% sodium 
chloride solution 
for injection)
Unit Dose 
Strength(s)
As detailed in the 
investigational 
product manual 
(IPM)
As detailed in the 
IPM
As detailed in the 
IPM
Not applicable 
(N/A)
Targeted 
Influenza Strains
As recommended 
by WHO for cell 
culture or 
recombinant-based 
vaccines 
(2023-2024 
northern 
hemisphere 
influenza season)a
N/A
As recommended 
by WHO for cell 
culture or 
recombinant-based 
vaccines 
(2023-2024 
northern 
hemisphere 
influenza season)a
N/A
Dosage Level(s)
BNT162b2 
(Omi XBB.1.5) 
30 µg
RIV 180 µg
30 µg mRNA
180 µg 
Recombinant 
protein
0.5 mL
Route of 
Administration
Intramuscular 
injection
Intramuscular 
injection
Intramuscular 
injection
Intramuscular 
injection
Sourcing
Provided centrally 
by the sponsor
Provided centrally 
by the sponsor
Provided centrally 
by the sponsor
Provided centrally 
by the sponsor
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Study Intervention(s)
Packaging and 
Labeling
Study intervention 
will be generated 
by mixing the 
following at the 
site at the 
dose-level 
combinations 
detailed below:

BNT162b2 
(Omi 
XBB.1.5)

RIV 
Each vial will be 
labeled per country 
requirement
Study intervention 
will be provided in 
a glass vial as 
open-label supply. 
Each vial will be 
labeled per country 
requirement
Study intervention 
will be provided as 
either a PFS or a 
glass/plastic vial as 
open-label supply
Study intervention 
will be provided in 
a plastic vial as 
open-label supply
Single Reference 
Safety Document 
(SRSD)
Combined 
investigator’s 
brochures (IBs)
IB
Flublok IB
N/A
a.
For the 2023-2024 influenza season, Flublok Quadrivalent is formulated to contain 180 µg HA per 
0.5-mL dose, with 45 µg HA of each of the following 4 influenza virus strains: A/West Virginia/30/2022 
(A/Wisconsin/67/2022 pdm09-like virus) (H1N1), A/Darwin/6/2021 (H3N2), B/Austria/1359417/2021,
and B/Phuket/3073/2013.
Statistical Methods:
The sample size is not based on any formal hypothesis test. All statistical analyses will be 
descriptive. Data from Phase 1 and Phase 2 participants will be combined for the safety and 
immunogenicity analyses.
The safety primary objective will be evaluated by descriptive summary statistics for local 
reactions, systemic events, AEs, and SAEs for each vaccine group. The immunogenicity 
primary objective will be evaluated descriptively by GMTs and GMFRs of SARS-CoV-2 
Omicron (XBB.1.5)–neutralizing titers and strain-specific HAI titers (for the seasonal strains 
recommended by WHO), percentages of participants with seroresponse to SARS-CoV-2 
Omicron (XBB.1.5), percentages of participants with HAI seroconversion and HAI 
titers ≥1:40, and the associated 2-sided 95% CIs, for each vaccine group. 
Ethical Considerations:
Potential risks to individual participants may include the following, mitigations for which are 
detailed in the protocol:

The safety profile of administering BNT162b2 and RIV concomitantly as a single 
vaccine is not yet fully characterized, so the full extent of risks is unknown.
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
Local reactions, such as injection site redness, injection site swelling, and injection site 
pain, and systemic events, such as fever, fatigue, headache, chills, vomiting, diarrhea,
muscle pain, and joint pain.

Cases of anaphylaxis, myocarditis, and pericarditis have been reported after authorization 
in recipients of BNT162b2. 

Venipuncture will be performed during the study. There is the risk of bleeding, bruising, 
hematoma formation, and infection at the venipuncture site.
Benefits to individual participants may be:

Receipt of at least 1 licensed vaccine against COVID-19 or influenza at no cost to the 
participant, and provision of the immunogenicity results.

Contributing to research to help others.
1.2. Schema
Phase 1
N = 80
Group 1
BNT162b2/RIV (1.0 mL)
+
placebo (0.5 mL)
Group 2
RIV (0.5 mL)
+
BNT162b2 (0.3 mL)
Group 3
BNT162b2 (0.3 mL)
+
placebo (0.5 mL)
Group 4
RIV (0.5 mL)
+
placebo (0.5 mL)
Phase 1a (Participants 50 through 64 years of age)
Sentinel
n = 10
Sentinel
n = 10
Sentinel
n = 10
Sentinel
n = 10
Sponsor Safety Data Reviewa
Phase 1b (Participants ≥65 years of age)
n = 10
n = 10
n = 10
n = 10
IRCb
Phase 2 N = 560
Participants ≥50 years of age
n = 140
n = 140
n = 140
n = 140
a.
Progression of the study will occur upon confirmation of an acceptable safety assessment of data 
accumulated after at least 24 hours and up to 7 days after vaccination.  
b.
Progression of the study will occur upon confirmation of an acceptable safety assessment of data 
accumulated after at least 72 hours and up to 7 days after vaccination, once approximately 
20 participants in each vaccine group have been vaccinated.  
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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Table 1.
Schedule of Activities
Visit Identifier
1
2
3
Notes
Visit Window
Day 1
28 to 35 Days 
After Visit 1
175 to 189 
Days After 
Visit 1
Day 1 = Day of Vaccination
Visit Description
Vaccination
4-Week 
Follow-Up 
Visit
6-Month 
Follow-Up 
Visit
Visit Type/Location
Site
Site
Site
Obtain informed consent
X

Informed consent should be obtained prior 
to undergoing any study-specific 
procedures.

See Section 10.1.3 for additional 
information.
Assign participant number
X
Obtain demography and medical history data 
X
Perform clinical assessment, including oral 
temperature and seated blood pressure
X
Including, if indicated, a physical examination.
Measure height and weight
X
See Section 8.3.1 for additional information.
Collect nonstudy vaccine information, including 
COVID-19 and influenza vaccine information
X
X
X
See Section 6.9.1 for additional information.
Perform urine pregnancy test on WOCBP
X
See Section 8.3.6 for additional information. 
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Table 1.
Schedule of Activities
Visit Identifier
1
2
3
Notes
Visit Window
Day 1
28 to 35 Days 
After Visit 1
175 to 189 
Days After 
Visit 1
Day 1 = Day of Vaccination
Visit Description
Vaccination
4-Week 
Follow-Up 
Visit
6-Month 
Follow-Up 
Visit
Visit Type/Location
Site
Site
Site
Confirm use of contraceptives (if appropriate)
X
X
See Section 5.3.1 for additional information.
Confirm eligibility
X
See Section 5 for additional information.
Review temporary delay criteria
X
See Section 5.5 for additional information.
Obtain randomization number and study intervention 
allocation
X
At registration, the participant enrollment 
number and dose-level allocation are assigned.
Collect blood sample for immunogenicity assessment
~20 mL
~20 mL
~20 mL

See Section 8.2 for additional information.

For laboratory collection volumes, see the 
laboratory manual.
Administer study intervention
X
Postvaccination observation (at least 30 minutes) and 
assessment of immediate events
X
Explain participant communication methods (including 
for reactogenicity e-diary completion), assist the 
participant with downloading the application, or issue 
provisioned device, if required
X
See Section 8.3.4 for additional information.
Provide/ensure the participant has a thermometer and 
measuring device
X
Review reactogenicity e-diary data (daily review is 
optimal during the active reactogenicity e-diary period 
[Days 1 through 7])
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Table 1.
Schedule of Activities
Visit Identifier
1
2
3
Notes
Visit Window
Day 1
28 to 35 Days 
After Visit 1
175 to 189 
Days After 
Visit 1
Day 1 = Day of Vaccination
Visit Description
Vaccination
4-Week 
Follow-Up 
Visit
6-Month 
Follow-Up 
Visit
Visit Type/Location
Site
Site
Site
Site reviews e-diary data with participant follow-up 
until ongoing symptom/medication resolution, if 
applicable
X
X
Review the participant’s e-diary data and record 
assessment in the CRF. Assess compliance, and 
any medically attended events (including 
hospitalizations). For symptoms still ongoing, 
continue to follow up until resolution, and 
document and record stop dates in the CRF.
Collect reactogenicity e-diary medication use
X
Collect AEs and SAEs as appropriate
X
X
X

See Section 8.4 for additional information.

AEs are collected from the completion of 
informed consent through Visit 2. SAEs are 
collected from the completion of informed 
consent through the end of study 
participation. Additionally, any AEs 
occurring up to 48 hours after a blood draw 
must be recorded.
Collect e-diary or assist the participant with deleting 
the application
X
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2. INTRODUCTION
2.1. Study Rationale 
This Phase 1/2 study will evaluate the safety, tolerability, and immunogenicity of licensed 
BNT162b2 (Omi XBB.1.5) and RIV when administered together in a single injection to
healthy adults 50 years of age or older.
Annual vaccine programs for SARS-CoV-2 and influenza are likely to run concurrently. In 
practice, BNT162b2 may be given simultaneously with licensed influenza vaccines.1,2
Combining BNT162b2 with RIV would allow for a single injection and could increase the 
likelihood that persons seeking either vaccination against SARS-CoV-2 or influenza would 
opt to protect themselves against both pathogens.
2.2. Background 
SARS-CoV-2, a novel β-coronavirus, is a highly transmissible and pathogenic respiratory 
virus responsible for the ongoing COVID-19 pandemic. Studies of SARS-CoV-2 and 
SARS-CoV, a closely related coronavirus that caused the 2003 SARS pandemic, 
demonstrated that effective antibody protection could be achieved through spike-specific 
antibodies.3,4 Therefore, vaccines targeting the spike protein of SARS-CoV-2 have been used 
as a critical mitigation strategy for the COVID-19 pandemic.
BNT162b2 (Comirnaty®) is an mRNA-based vaccine that, as of January 2023, has been 
granted full marketing authorization, conditional marketing authorization, EUA, or 
temporary authorization in a total of more than 184 countries for the prevention of 
COVID-19 caused by SARS-CoV-2.5 The original version of BNT162b2 encodes the 
ancestral Wuhan-Hu-1 strain spike glycoprotein. In the US, it has been fully licensed for use 
in individuals 12 years of age and above as of 08 July 2022.6
With high background rates of population seropositivity, bivalent (original/Omi BA.4/BA.5) 
mRNA vaccines continued to provide effective protection against Omicron-related 
COVID-19,7,8,9,10,11,12 including during periods of early XBB sublineage dominance.8  
Additional bivalent (original/Omi BA.4/BA.5) mRNA doses have been reported to have 
higher VE against Omicron than the original vaccine,13 supporting the hypothesis that better 
strain-matched vaccines improve protection against COVID-19. However, as of May 2023, 
the descendent sublineages of Omicron XBB (eg, XBB.1.5, XBB.1.16, XBB.1.9) have 
shown improved transmissibility and reduced susceptibility to neutralization by the bivalent 
(original/Omi BA.4/BA.5) compared to earlier Omicron strains (eg, BA.1, BA.4, BA.5).7
Multiple reports have suggested potential waning VE of bivalent BA.4/BA.5 mRNA 
vaccination against severe illness, as well as less severe endpoints (ie, urgent/emergency 
care), roughly 2 to 6 months following vaccination.12,14,15 These data suggest that continual 
virus evolution toward improved viral fitness, immune escape, and transmission is impacting 
VE over time.16 On 12 September 2023, the Advisory Committee on Immunization Practices 
(ACIP) recommended vaccination for all persons aged ≥6 months with the updated 
2023-2024 COVID-19 vaccine including monovalent BNT162b2 (Omi XBB.1.5).17
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Influenza is a major cause of morbidity and mortality worldwide, occurring in annual 
seasonal epidemics and occasionally in global pandemics.18 Symptomatic influenza infection 
causes a febrile illness with respiratory and systemic symptoms,19 although it may often be 
asymptomatic.20 The risk of complications and hospitalization from influenza are higher in 
people ≥65 years of age, young children, and people with certain underlying medical 
conditions. In the US, since 2010 an average of 445,000 hospitalizations per year are related 
to influenza,21 while the annual global number of deaths is estimated to range from almost 
300,000 to over 600,000.22
Influenza viruses are part of the Orthomyxoviridae family and are divided into 4 genera 
(3 of which are known to infect humans [A, B, and C]).21,23 Influenza A viruses are further 
classified into subtypes based upon the membrane glycoproteins, HA and NA.23 The RNA 
genome is segmented, which allows for genetic reassortment among influenza A viruses.23
This genetic instability can result in the phenomenon known as antigenic shift, involving a 
major change in one (HA) or both (HA + NA) of the surface antigens, which, if efficiently 
transmissible, can result in a pandemic. More common are multiple point mutations in the 
genome, leading to more minor changes in the HA and NA, known as antigenic drift.21 This 
genetic instability, which can occur in influenza A, B, and C, is what necessitates vaccines 
that are tailored annually.21
Most available influenza vaccines require the culturing of influenza virus in chicken egg 
cells. The growth process not only introduces opportunity for mutations that are antigenically 
mismatched to the circulating strain, but the process also requires many months.24 Flublok is 
a unique influenza vaccine that harnesses recombinant technology to produce purified HA 
within 6 to 8 weeks.24,25  
There is a recommendation in the US for routine annual influenza vaccination for all persons 
aged ≥6 months who do not have contraindications.26
2.2.1. Clinical Overview
2.2.1.1. BNT162b2
Study C4591001 (NCT04368728) was a Phase 1/2/3 trial in ~47,000 participants, designed to 
generate safety, tolerability, immunogenicity, and efficacy data from a novel RNA-based 
vaccine candidate. The trial was conducted in a heterogeneous study population: eligible 
participants ≥12 years of age who are healthy, including those participants with stable 
chronic medical conditions, including HIV-, HCV-, and HBV-positive participants.27
Available immunogenicity data from Phase 1 participants showed that BNT162b2 induced a 
robust IgG-binding response to S1 and a SARS-CoV-2–neutralizing response. 
Immunogenicity substantially increased following the second dose of vaccine. BNT162b2 
induces a strong antigen-specific Th1-skewed CD4+ response and a strong antigen-specific 
CD8+ response.
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In a mid–November 2020 analysis of 36,523 participants randomized 1:1 to vaccine or 
placebo and who were included in the per-protocol efficacy analysis population of 
participants without evidence of SARS-CoV-2 infection prior to 7 days after completion of 
the vaccination schedule, the efficacy in preventing confirmed COVID-19 occurring at least 
7 days after the second dose of vaccine was 95.0%, with 8 COVID-19 cases in the active 
vaccine group and 162 COVID-19 cases in the placebo group.27
In a subsequent analysis of 927 confirmed symptomatic cases of COVID-19, an efficacy rate 
of 91.3% was observed for BNT162b2 in preventing such cases occurring between 7 days 
and 6 months after the second dose.28 Furthermore, from the same analysis, BNT162b2 was 
shown to have an efficacy of: 

100% in preventing severe disease as defined by the CDC.

95.3% in preventing severe disease as defined by the FDA.

100% in preventing COVID-19 cases in South Africa, where the B.1.351 lineage was 
prevalent at the time of analysis.
Safety data from approximately 38,000 participants at least 16 years of age randomized 
1:1 to vaccine or placebo with a median of 2 months of follow-up after the second dose 
demonstrated a favorable safety profile. Available safety data from all participants enrolled 
through the 14 November 2020 data cutoff (N = 43,252), which includes late enrollment of 
additional adolescent and adult participants, were consistent with the safety profile for the 
approximately 38,000 participants with a median follow-up of 2 months and also did not 
raise specific safety concerns.27
Considering the continuous emergence of variants with cumulative mutations in the spike 
protein that are resilient to the existing immune response, development of enhanced 
variant-specific vaccines that generate improved immune responses against the variants 
remains imperative, to better protect individuals against COVID-19. 
WHO issued its statement on the antigen composition of COVID-19 vaccines on 
18 May 2023 recommending use of a monovalent XBB.1 descendent lineage, such as 
XBB.1.5, as the vaccine antigen.7 The EMA released similar guidance on 06 June 2023 
recommending that a monovalent vaccine targeting the XBB.1 descendent lineages be 
administered beginning in autumn 2023.29 On 11 September 2023, the FDA approved 
authorization of a monovalent vaccine targeting the XBB.1.5 Omicron subvariant.30,31
2.2.1.2. RIV
RIV was studied in a Phase 3 multicenter, randomized, double-blind controlled trial in adults 
65 years of age and older during the 2006-2007 influenza season where participants were 
randomized to RIV or a licensed trivalent influenza vaccine. The frequency and severity of 
injection site reaction and systemic events after immunization were similar in both groups.
RIV was found to be both safe and well tolerated.32,33
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Trivalent RIV was studied in a randomized trial study of 4648 individuals 18 to 55 years of 
age during the 2007-2008 influenza season. RIV was well tolerated, immunogenic, and 
protective against culture-confirmed influenza.33,34
Trivalent RIV was studied in a Phase 3 observer-blind study in heathy adults 50 to 64 years 
of age during the 2007-2008 influenza season and was found to be both safe and
immunogenic.33,35
Quadrivalent RIV was studied in an observer-blind, randomized, active-controlled, Phase 3 
study of 1350 individuals aged 18 to 49 years during the 2014-2015 influenza season. RIV 
was compared directly with a standard-dose, egg-grown, quadrivalent-inactivated influenza 
vaccine for immunogenicity and safety. Quadrivalent RIV showed comparable safety, 
tolerability, and immunogenicity to inactivated quadrivalent influenza vaccine.36
2.3. Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of BNT162b2 (Omi XBB.1.5)/RIV may be found in the combined IBs, which 
is the SRSD for this study. The SRSD for BNT162b2 (Omi XBB.1.5) and RIV is the 
Comirnaty® IB and Flublok Quadrivalent IB, respectively. Refer to the Study Intervention(s) 
table in Section 6.1 for a complete description of SRSDs.
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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): BNT162b2 (Omi XBB.1.5)/RIV administered together as a single injection or BNT162b2 (Omi XBB.1.5) and RIV administered 
simultaneously
Allergic reactions/anaphylaxis may occur.
Allergic reactions have been observed with an 
unknown frequency.
Sites will have appropriate medication and
supportive measures for management of an acute 
hypersensitivity reaction.
Local and systemic reactions to the vaccine may 
occur (injection site redness, injection site swelling, 
and injection site pain; fever, fatigue, headache, 
chills, vomiting, diarrhea, muscle pain, and joint 
pain) following vaccination.
These are common adverse reactions seen with other 
vaccines,37 as well as the COVID-19 vaccine 
BNT162b2. The most common events reported in a 
large-scale efficacy study with BNT162b2 
(C4591001) were mild to moderate pain at the 
injection site, fatigue, and headache.27 The most 
common adverse reactions seen in a 
placebo-controlled safety and efficacy trial of RIV 
were local injection site pain, muscle aches, 
headache, and fatigue or lack of energy.34   
Slightly increased reactogenicity has been shown 
when a COVID-19 booster is coadministered with 
an influenza vaccine.38
The study employs the use of a reactogenicity 
e-diary, which allows the investigator to monitor 
local reactions and systemic events in real time after
each vaccination through an electronic portal. Severe 
reactions will require an unscheduled telephone call, 
and visit if required, to be conducted per protocol.
All study participants will be observed for at least 
30 minutes after vaccination.
The safety profile of a novel vaccine is not yet fully 
characterized.
BNT162b2 (Omi XBB1.5)/RIV is a novel 
combination; however, the individual active 
components from which it is made have been shown 
to have a positive benefit/risk profile.
AE and SAE reports will be collected from the 
signing of the ICD through 4 weeks and 6 months, 
respectively, after vaccination.
All participants will be observed for at least 
30 minutes after vaccination.
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): BNT162b2 (Omi XBB.1.5)
This vaccine has the same modRNA platform and 
LNP formulation as the original BNT162b2; 
therefore, the safety profile is expected to be similar 
to that of BNT162b2, ie, local reactions, such as 
injection site redness, injection site swelling, and 
injection site pain, and systemic events, such as 
fever, fatigue, headache, chills, vomiting, diarrhea, 
muscle pain, and joint pain.
Other key risks identified for BNT162b2 are 
lymphadenopathy; hypersensitivity reactions, such 
as rash, pruritus, urticaria, angioedema, and 
anaphylaxis; and myocarditis and pericarditis.
These are common adverse reactions seen with other 
vaccines as well as the COVID-19 vaccine.
Data available from the C4591001 study 
(with BNT162b2) showed low incidence of severe 
or serious events and no clinically concerning safety 
observations across the safety population and within 
demographic subgroups based on age, sex, 
race/ethnicity, country, and baseline SARS-CoV-2 
status.27
Anaphylaxis: Frequency not known.
Myocarditis and pericarditis: Very rare cases of 
myocarditis and pericarditis have been reported 
following vaccination with modRNA SARS-CoV-2 
vaccines after authorization. Typically, the cases 
have occurred more often in younger men and after 
the second dose of the vaccine and within 14 days 
after vaccination. These are generally mild cases, 
and individuals tend to recover within a short time 
following standard treatment and rest. Healthcare 
professionals should be alert to the signs and 
symptoms of myocarditis and pericarditis in vaccine 
recipients.
Postauthorization safety data surveillance has 
confirmed the safety profile observed in Study 
C4591001 and has resulted in identification of some 
additional adverse reactions (risks) as noted in the 
SRSD.
Local reactions and systemic events will be recorded 
using a reactogenicity e-diary to monitor local 
reactions and systemic events in real time after 
vaccination.
AE and SAE reports will be collected from the 
signing of the ICD through 4 weeks and 6 months, 
respectively, after vaccination.
Specific reference to these risks is made within the 
ICD, with instruction to contact a healthcare 
professional if a case is suspected.
For anaphylaxis, there is an on-site 30-minute 
observation period after vaccination.
Instructions for handling suspected cases of 
myocarditis and pericarditis are found in 
Section 8.10.5.
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): RIV (Flublok)
Local and systemic reactions to the vaccines may 
occur (injection site redness, injection site swelling, 
and injection site pain; fever, fatigue, headache, 
chills, vomiting, diarrhea, new or worsened muscle 
pain, and new or worsened joint pain) following 
vaccination.
These are common reactions seen with other 
vaccines as well as RIV.33,37
Anaphylaxis: Frequency not known. 
GBS: The 1976 swine influenza vaccine was 
associated with an increased frequency of GBS. 
Evidence for a causal relation of GBS with other 
influenza vaccines is inconclusive; if an excess risk 
exists, it is probably slightly more than 1 additional 
case per 1 million persons vaccinated. If GBS has 
occurred within 6 weeks after receipt of a prior 
influenza vaccine, the decision to give Flublok 
should be based on careful consideration of the 
potential benefits and risks.33
Altered immunocompetence: If RIV is administered 
to immunocompromised individuals, including 
persons receiving immunosuppressive therapy, the 
immune response may be diminished.33
Limitations of vaccine effectiveness: Vaccination 
with RIV may not protect all vaccine recipients.33
AE and SAE reports will be collected from the 
signing of the ICD through 4 weeks and 6 months, 
respectively, after vaccination.
All study participants will be observed for at least 
30 minutes after vaccination.
For anaphylaxis, there is an on-site 30-minute
observation period after vaccination. 
Immunocompromised individuals and individuals 
receiving immunosuppressive therapies will be 
excluded from Phase 1 and 2 of this study. 
Study Procedures 
Venipuncture will be performed during the study.
There is the risk of bleeding, bruising, hematoma 
formation, and infection at the venipuncture site.
Only appropriately qualified personnel will obtain 
the blood draw.
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2.3.2. Benefit Assessment
See Section 2.3 for overall study risks. Benefits to individual participants enrolled in this 
study may be:

Receipt of an efficacious or potentially efficacious COVID-19 vaccine.

Receipt of an efficacious or potentially efficacious influenza vaccine.

Receipt of both a COVID-19 vaccine and an influenza vaccine.

Contributing to research to help others.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with BNT162b2 (Omi XBB.1.5)/RIV are justified by the anticipated 
benefits that may be afforded to healthy participants.
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
Safety
To describe the safety and 
tolerability of the study
interventions

Local reactions (pain at the 
injection site, redness, and 
swelling) 

Systemic events (fever, 
fatigue, headache, chills, 
vomiting, diarrhea, new or 
worsened muscle pain, and 
new or worsened joint pain)

AEs

SAEs
The percentage of participants 
receiving at least 1 dose of study 
intervention reporting:

Local reactions for up to 
7 days following vaccination

Systemic events for up to 
7 days following vaccination

AEs from vaccination 
through 4 weeks after 
vaccination

SAEs from vaccination 
through 6 months after 
vaccination
Immunogenicity
To describe the immune responses 
elicited by BNT162b2 
(Omi XBB.1.5)/RIV, BNT162b2 
(Omi XBB.1.5) + RIV
coadministered, and BNT162b2 
(Omi XBB.1.5) and RIV
administered alone (4 weeks after 
vaccination)
SARS-CoV-2 
Omicron (XBB.1.5)–neutralizing 
titers
In participants complying with the 
key protocol criteria (evaluable 
participants):

GMTs before vaccination and 
at 4 weeks after vaccination 

GMFR from before 
vaccination to 4 weeks after 
vaccination 

Percentage of participants 
with seroresponsea at 4 weeks 
after vaccination
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Objectives
Endpoints
Estimands
HAI titers against the seasonal 
strains recommended by WHO for 
the northern hemisphere 2023-2024 
influenza season
In participants complying with the 
key protocol criteria (evaluable 
participants):

GMTs before vaccination and 
at 4 weeks after vaccination

GMFRs from before 
vaccination to 4 weeks after 
vaccination 

The percentages of 
participants achieving HAI
seroconversionb at 4 weeks 
after vaccination 

The percentages of 
participants with HAI titers 
≥1:40 before vaccination and 
at 4 weeks after vaccination
Exploratory:
Exploratory:
Exploratory:
To describe the immune responses 
elicited by BNT162b2 
(Omi XBB.1.5)/RIV, BNT162b2 
(Omi XBB.1.5) + RIV 
coadministered, and BNT162b2 
(Omi XBB.1.5) and RIV 
administered alone (6 months
after vaccination)
SARS-CoV-2 
Omicron (XBB.1.5)–neutralizing 
titers
In participants complying with the 
key protocol criteria (evaluable 
participants):

GMTs before vaccination and 
at 6 months after vaccination 

GMFR from before 
vaccination to 6 months after 
vaccination 

Percentage of participants 
with seroresponsea at 
6 months after vaccination
HAI titers against the seasonal 
strains recommended by WHO for 
the northern hemisphere 2023-2024 
influenza season
In participants complying with the 
key protocol criteria (evaluable 
participants):

GMTs before vaccination and 
at 6 months after vaccination

GMFRs from before 
vaccination to 6 months after 
vaccination 

The percentages of 
participants achieving HAI
seroconversionb at 6 months 
after vaccination 

The percentages of 
participants with HAI titers 
≥1:40 before vaccination and 
at 6 months after vaccination
To describe the immune response 
to emerging variants (under 
monitoring, of interest, and/or of 
concern)
SARS-CoV-2–neutralizing titers
and/or HAI titers for variants 
(under monitoring, of interest, 
and/or of concern) not already 
specified
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Objectives
Endpoints
Estimands
To descriptively compare the
immune responses between 
vaccine groups
SARS-CoV-2 Omicron 
(XBB.1.5)–neutralizing titers and 
HAI titers for the seasonal strains 
recommended by WHO
GMRs and differences in 
percentage of participants with 
seroresponse or seroconversion
between vaccine groups
To describe the immune response 
elicited by RIV using virus 
microneutralization assays
HAI titers against the seasonal 
strains recommended by WHO for 
the northern hemisphere 2023-2024 
influenza season
a.
Seroresponse is defined as achieving a ≥4-fold rise from baseline (before the study vaccination). If the 
baseline measurement is below the LLOQ, the postvaccination measure of ≥4 × LLOQ is considered 
seroresponse.
b.
Seroconversion is defined as an HAI titer 1:10 prior to vaccination and ≥1:40 at the time point of 
interest, or an HAI titer of ≥1:10 prior to vaccination with a minimum 4-fold rise at the time point of 
interest.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 1/2 single-blind (site- and sponsor-unblinded) study to evaluate the safety, 
tolerability, and immunogenicity of licensed BNT162b2 (Omi XBB.1.5) and RIV 
administered together as a single injection (referred to as BNT162b2 [Omi XBB.1.5]/RIV) in 
healthy adults 50 years of age or older. 
The safety, tolerability, and immunogenicity of BNT162b2 (OmiXBB1.5)/RIV administered 
as a single injection will be compared to BNT162b2 (Omi XBB.1.5) and RIV administered 
simultaneously as 2 separate injections (coadministered), and to BNT162b2 (Omi XBB.1.5)
or RIV when administered alone. 
Across Phases 1 and 2, approximately 640 participants in total will be randomized with an 
equal randomization ratio (1:1:1:1) to each of the following vaccine groups and stratified by 
age group (50 through 64 years of age and ≥65 years of age):  

Group 1: BNT162b2 (Omi XBB.1.5)/RIV (as a single injection) administered in the left 
deltoid and placebo administered in the right deltoid

Group 2: BNT162b2 (Omi XBB.1.5) administered in the left deltoid and RIV
administered in the right deltoid

Group 3: BNT162b2 (Omi XBB.1.5) administered in the left deltoid and placebo
administered in the right deltoid

Group 4: RIV administered in the left deltoid and placebo administered in the right 
deltoid
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During Phase 1, a total of ~20 participants will be enrolled in each vaccine group. Enrollment 
of participants in each vaccine group will be controlled such that ~10 participants 50 through 
64 years of age (sentinel participants, considered Phase 1a) can be vaccinated in each of the 
groups on the first day. This will be monitored by the sponsor, who will inform sites to pause 
enrollment once the target has been reached. Vaccination of the remaining ~40 participants
(~10 per vaccine group) will commence no sooner than 24 hours after this safety pause. The 
participants vaccinated after the safety pause will be ≥65 years of age (considered Phase 1b).
Once ~20 participants per vaccine group have been vaccinated in Phase 1, the IRT system 
will block any further randomization, pending a review of at least 72 hours of safety data for 
all participants by the IRC. The outcome of the safety data review will be documented in a 
memo, which will be circulated to all sites prior to starting enrollment in Phase 2. In Phase 2, 
140 participants 50 years of age or older will be enrolled in each of the 4 vaccine groups
(Table 2). Participants will be stratified by age group, 50 through 64 years of age and 
≥65 years of age.
Table 2.
Phase 1/2 Vaccine Group Summary
Vaccine Group 
Number
Vaccine Group Description
Phase 1a
(Number of 
Participants per 
Vaccine Group)
Phase 2b
(Number of 
Participants per 
Vaccine Group)
1
BNT162b2 (Omi XBB.1.5)/RIV 
and placebo
20
140
2
BNT162b2 (Omi XBB.1.5) and 
RIV
20
140
3
BNT162b2 (Omi XBB.1.5) and 
placebo
20
140
4
RIV and placebo
20
140
a.
Phase 1a participants will be 50 through 64 years of age at Visit 1 (Day 1). Phase 1b participants will be 
≥65 years of age at Visit 1 (Day 1).
b.
Phase 2 participants will be 50 years of age or older at Visit 1 (Day 1).
Prespecified local reaction and systemic event data will be collected in an e-diary during the 
7 days, or longer for ongoing symptoms, after study intervention (ie, from Day 1, the day of 
vaccination, until symptom resolution), as well as any medication taken during this period to 
treat any pain symptoms or fever. 
Blood samples of approximately 20 mL will be collected from all participants for 
immunogenicity assessments prior to vaccination and at 4 weeks and 6 months after 
vaccination.
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Following vaccination, AEs will be collected from informed consent signing through Visit 2
(approximately 4 weeks after vaccination), and SAEs will be collected from informed 
consent signing through Visit 3 (approximately 6 months after vaccination). In addition, AEs 
occurring up to 48 hours after blood draws will also be collected.
4.2. Scientific Rationale for Study Design
The overall scientific rationale for the study design is presented in Section 2.1.
4.2.1. Choice of Contraception/Barrier Requirements 
Human reproductive safety data are not available for the RIV used in this study, but there is 
no suspicion of human teratogenicity based on the intended pharmacology of the 
compound. The use of a highly effective method of contraception is required 
(see Appendix 4).
4.3. Justification for Dose
4.3.1. Monovalent BNT162b2 (Omi XBB.1.5)
The 30-μg dose level of BNT162b2 was shown to be effective and is licensed for use in the 
US.39
4.3.2. RIV
The 180-μg dose level of RIV was shown to be effective and is licensed for use in the US.33
4.3.3. BNT162b2 (Omi XBB.1.5)/RIV
This will be a combination of BNT162b2 (Omi XBB.1.5) and RIV using the dose levels 
detailed in Section 4.3.1 and Section 4.3.2.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study.
A participant is considered to have completed the study if they have completed the last visit 
of the study.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. If a 
prescreening tool is utilized for study recruitment purposes, it will include collection of 
information that reflects the enrollment of a diverse participant population including, where 
permitted under local regulations, age, sex, race, and ethnicity. The following eligibility 
criteria are designed to select participants for whom participation in the study is considered 
appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular participant is suitable for this protocol.
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Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
Individual participants may not be enrolled in this study more than once.
Note: "Enrolled" means a participant's agreement to participate in a clinical study following 
completion of the informed consent process and randomization.
5.1. Inclusion Criteria
Participants are eligible to be included in this study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants aged 50 years or older at Visit 1 (Day 1). 

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Disease Characteristics:
Not applicable. 
Other Inclusion Criteria:
2. Participants who are willing and able to comply with all scheduled visits, the 
investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Healthy participants who are determined by medical history, physical examination 
(if required), and clinical judgment of the investigator to be eligible for inclusion in the 
study.

Note: Healthy participants with preexisting stable disease, defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease 
during the 6 weeks before enrollment, can be included. 
4. Capable of giving signed informed consent as described in the protocol, which includes 
compliance with the requirements and restrictions listed in the ICD and in this protocol.
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5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Any medical or psychiatric condition including recent (within the past year) or active 
suicidal ideation/behavior or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the 
study.
2. Known infection with HIV, HCV, or HBV.
3. History of severe adverse reaction associated with any vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study interventions.
4. Participants 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, multiple sclerosis, 
Sjögren’s syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, 
autoimmune thyroiditis, temporal arteritis, psoriasis, and/or insulin-dependent diabetes 
mellitus.
5. Immunocompromised individuals with known or suspected immunodeficiency, 
determined by history and/or laboratory/physical examination.

Note: Individuals who have had a splenectomy or have functional asplenia will be 
considered ineligible.
6. Current heart disease, uncontrolled hypertension, or a prior history of myocarditis or 
pericarditis.

Note: Hypertension that has been controlled a minimum of 12 weeks, stable coronary 
artery disease, and stable mild valvular disease are not exclusionary.
7. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
8. Women who are pregnant, plan to become pregnant during the study, or are 
breastfeeding.
9. Prior history of ischemic stroke or transient ischemic attack.
10. Prior history of GBS.
11. Participants with a calculated BMI of ≥35.
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Prior/Concomitant Therapy:
12. Receipt of chronic medications with known systemic immunosuppressant effects 
(including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days 
before enrollment through conclusion of the study.

Note: Systemic corticosteroids are defined as those administered for ≥14 days at a 
dose of ≥20 mg/day of prednisone or equivalent (eg, for cancer or an autoimmune 
disease) or planned receipt throughout the study. Inhaled/nebulized, intra-articular, 
intrabursal, or topical (skin or eyes) corticosteroids are permitted.
13. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies used for 
the treatment or prevention of COVID-19 or those that are considered 
immunosuppressive, from 90 days before study intervention administration, or planned 
receipt throughout the study.
14. Vaccination with any investigational or licensed influenza vaccine within 6 months 
(180 days) before study intervention administration, or ongoing receipt of chronic 
antiviral therapy with activity against influenza.
15. Vaccination with any investigational or licensed COVID-19 vaccine within 6 months 
(180 days) before study intervention administration.
Prior/Concurrent Clinical Study Experience:
16. Participation in other studies involving administration of an investigational product
within 28 days prior to, and/or during, participation in this study.

Note: In addition to administration of investigational products, study interventions 
may include additional procedures, such as collection of biological samples. 
Therefore, participants may not be in another study whereby procedures, such as 
respiratory illness visits, may interfere with compliance with this study’s protocol.
Diagnostic Assessments:
Not applicable.
Other Exclusion Criteria:
17. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members.
18. Deprived of freedom by an administrative or court order, or in an emergency setting, or 
hospitalized involuntarily.
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19. Current alcohol abuse or drug addiction that in the opinion of the investigator might 
interfere with the study conduct or completion.
5.3. Lifestyle Considerations
5.3.1. Contraception 
The investigator or their designee, in consultation with the participant, will confirm that the 
participant is utilizing an appropriate method of contraception for the individual participant 
and their partner(s) from the permitted list of contraception methods (see Appendix 4,
Section 10.4.4) and will confirm that the participant has been instructed in its consistent and 
correct use. The investigator or designee will advise the participant to seek advice about the 
donation and cryopreservation of germ cells prior to the start of study intervention, if 
applicable.
At time points indicated in the SoA, the investigator or designee will inform the participant 
of the need to use acceptable effective contraception consistently and correctly and document 
the conversation and the participant’s affirmation in the participant’s chart. Participants need 
to affirm their consistent and correct use of at least 1 of the selected methods of 
contraception, considering that their risk for pregnancy may have changed since the last visit. 
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued and document the requirement to use an 
alternate protocol-specified method, including if the participant will no longer use abstinence 
as the selected contraception method, or if pregnancy is known or suspected in the participant 
or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the CONSORT 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, and any SAEs.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened under a different participant number, once eligibility criteria are met.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Administration of 
Study Intervention 
The following conditions may allow a participant to be randomized once the conditions have 
resolved and the participant is otherwise eligible. Participants meeting these criteria at Visit 1 
will be considered screen failures if enrollment has closed once the condition(s) has/have 
resolved.

A positive influenza or SARS-CoV-2 test result (NAAT or rapid antigen test) within the 
previous 28 days.
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
Current febrile illness (oral temperature ≥38.0°C [≥100.4°F]) or other acute illness within 
48 hours before study intervention administration.

Receipt of any nonstudy vaccine within 28 days before study intervention administration 
at Visit 1.

Anticipated receipt of any nonstudy vaccine within 28 days after study intervention 
administration at Visit 1.

Receipt of short-term (14 days) systemic corticosteroids at a dose of ≥20 mg/day of 
prednisone or equivalent. Study intervention administration should be delayed until 
systemic corticosteroid use has been discontinued for at least 28 days.

Note: Systemic corticosteroids administered at a dose of 20 mg/day of prednisone or 
equivalent are permitted. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study interventions are all prespecified investigational and medical devices, and other 
interventions (eg, surgical and behavioral), intended to be administered to the study 
participants during the study conduct.
6.1. Study Intervention(s) Administered
Participants will be enrolled and randomized to each of the following vaccine groups: 

Group 1: BNT162b2 (Omi XBB.1.5)/RIV (as a single injection) administered in the left 
deltoid and placebo administered in the right deltoid

Group 2: BNT162b2 (Omi XBB.1.5) administered in the left deltoid and RIV 
administered in the right deltoid

Group 3: BNT162b2 (Omi XBB.1.5) administered in the left deltoid and placebo 
administered in the right deltoid

Group 4: RIV administered in the left deltoid and placebo administered in the right 
deltoid
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Study Intervention(s)
Intervention Name
BNT162b2 
(Omi XBB.1.5)/RIV
BNT162b2 (Omi XBB.1.5)
RIV
Normal saline placebo
Type
mRNA and recombinant 
protein vaccine 
mRNA vaccine
Recombinant protein vaccine
Placebo
Use
Experimental
Comparator
Comparator
Placebo for blinding
IMP or NIMP/AxMP
IMP
IMP
IMP
IMP
Dose Formulation
Suspension for injection and 
Recombinant 
Suspension for injection
Solution for injection
Normal saline (0.9% sodium 
chloride solution for 
injection)
Unit Dose Strength(s)
As detailed in the IPM
As detailed in the IPM
As detailed in the IPM
N/A
Targeted Influenza Strains
As recommended by WHO 
for cell culture or 
recombinant-based vaccines 
(2023-2024 northern 
hemisphere influenza 
season)a
N/A
As recommended by WHO 
for cell culture or 
recombinant-based vaccines 
(2023-2024 northern 
hemisphere influenza 
season)a
N/A
Dosage Level(s)
BNT162b2 (Omi XBB.1.5) 
30 µg
RIV 180 μg
30 µg mRNA
180 μg Recombinant protein
0.5 mL
Route of Administration
Intramuscular injection
Intramuscular injection
Intramuscular injection
Intramuscular injection
Sourcing
Provided centrally by the 
sponsor
Provided centrally by the 
sponsor
Provided centrally by the 
sponsor
Provided centrally by the 
sponsor
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Study Intervention(s)
Packaging and Labeling
Study intervention will be 
generated by mixing the 
following at the site at the 
dose-level combinations 
detailed below:

BNT162b2 
(Omi XBB.1.5)

RIV
Each vial will be labeled per 
country requirement
Study intervention will be 
provided in a glass vial as 
open-label supply. Each vial 
will be labeled per country 
requirement
Study intervention will be 
provided as either a PFS or a 
glass/plastic vial as 
open-label supply
Study intervention will be 
provided in a plastic vial as 
open-label supply
SRSD
Combined IBs
IB
Flublok IB
N/A
a.
For the 2023-2024 influenza season, Flublok Quadrivalent is formulated to contain 180 µg HA per 0.5-mL dose, with 45 µg HA of each of the following 
4 influenza virus strains: A/West Virginia/30/2022 (A/Wisconsin/67/2022 pdm09-like virus) (H1N1), A/Darwin/6/2021 (H3N2), 
B/Austria/1359417/2021, and B/Phuket/3073/2013.
Study Arm(s)
Group
1
2
3
4
Arm Title
BNT162b2 
(Omi XBB.1.5)/RIV + 
normal saline placebo
BNT162b2 
(Omi XBB.1.5) + RIV
BNT162b2 (Omi XBB.1.5) + 
normal saline placebo
RIV + normal saline placebo
Arm Description
Participants will receive a 
single injection combination 
of BNT162b2 
(Omi XBB.1.5) (30 µg) and 
RIV (180 µg) administered
in the left deltoid and normal 
saline placebo administered
in the right deltoid at Visit 1 
(Day 1)
Participants will receive 
BNT162b2 (Omi XBB.1.5) 
(30 µg) administered in the 
left deltoid and RIV (180 µg) 
administered in the right 
deltoid at Visit 1 (Day 1)
Participants will receive 
BNT162b2 (Omi XBB.1.5)
(30 µg) administered in the 
left deltoid and normal saline 
placebo administered in the 
right deltoid at Visit 1 
(Day 1)
Participants will receive RIV 
(180 µg) administered in the 
left deltoid and normal saline 
placebo administered in the 
right deltoid
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6.1.1. Administration
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 must be available in accordance with local guidelines for standard 
immunization practices.
Administration of study interventions will be performed by an appropriately qualified, 
trained, and vaccine-experienced member of the study staff (eg, physician, nurse, physician’s 
assistant, nurse practitioner, pharmacist, or medical assistant) as allowed by local, state, and 
institutional guidance. 
Study intervention administration details will be recorded on the CRF.
Participants will receive 2 injections at Visit 1 as randomized in accordance with the SoA. 
Study intervention should be administered intramuscularly into the deltoid muscle of the 
appropriate arm as detailed in Table 3, and in such a way as to ensure that the participants 
remain blinded.
Table 3.
Anatomical Location for Study Intervention Administration
Vaccine Group Number
Left Deltoida
Right Deltoida
1
BNT162b2 (Omi XBB.1.5)/RIV
Placebo
2
BNT162b2 (Omi XBB.1.5)
RIV
3
BNT162b2 (Omi XBB.1.5)
Placebo
4
RIV
Placebo
a.
Study intervention will be administered in contralateral arms. Local reactions will be assessed at the 
injection site on both the left and right deltoids.
6.1.2. Medical Devices 
RIV and normal saline placebo may be provided as a PFS, in which case the PFS should be 
considered a medical device.
All medical device deficiencies (including malfunction, use error, and inadequate labeling) 
for the medical devices listed above shall be documented and reported by the investigator 
throughout the clinical investigation (see Section 8.4.9) and appropriately managed by the 
sponsor.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm that appropriate conditions (eg, temperature) 
have been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply, prepare, and/or administer study intervention. 
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3. All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a minimum, 
daily minimum and maximum temperatures for all site storage locations must be 
documented and available upon request. Data for nonworking days must indicate the 
minimum and maximum temperatures since previously documented upon return to 
business.
4. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with actions taken. The site should actively pursue options 
for returning the study intervention to labeled storage conditions, as soon as possible. 
Once an excursion is identified, the study intervention must be quarantined and not used 
until Pfizer provides permission to use the study intervention. Specific details regarding 
the excursion definition and information to report for each excursion will be provided to 
the site in the IPM.
5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the label. See the IPM for storage conditions of the study intervention.
6. Study interventions should be stored in their original containers.
7. The investigator, institution, head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records), such as 
the IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record. 
8. Further guidance and information for the final disposition of unused study interventions 
are provided in the IPM. All destruction must be adequately documented. If destruction is 
authorized to take place at the investigator site, the investigator must ensure that the 
materials are destroyed in compliance with applicable environmental regulations, 
institutional policy, and any special instructions provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IPM.
6.2.1. Preparation and Dispensing
See the IPM, package insert, or equivalent for instructions on how to prepare the study 
intervention for administration. Study intervention should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance. A second staff member will verify the 
dispensing.
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6.3. Assignment to Study Intervention
Allocation (randomization) of participants to study arms will proceed through the use of an 
IRT system (IWR). The site personnel (study coordinator or specified designee) will be 
required to enter or select information including but not limited to the user’s ID and 
password, the protocol number, and the participant number. The site personnel will then be 
provided with a randomization number corresponding to the assigned study intervention.* 
The IRT system will provide a confirmation report containing the participant number, 
randomization number, and study intervention allocation assigned. Confirmation report must 
be stored in the site’s files.
* Do not randomize until eligibility is confirmed and the participant is present.
Study intervention will be dispensed at the study visits summarized in the SoA. 
The study-specific IRT reference manual and IPM will provide the contact information and 
further details on the use of the IRT system.
6.4. Blinding
This is a single-blind study. 
6.4.1. Blinding of Participants
Participants will be blinded to their assigned study intervention.
6.4.2. Blinding of Site Personnel
Investigators and other site staff will be unblinded to participants’ assigned study 
intervention. 
6.4.3. Blinding of the Sponsor
Sponsor staff will be unblinded to participants’ assigned study intervention. 
6.4.4. Breaking the Blind 
Not applicable.
6.5. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention.
6.6. Dose Modification
Not applicable.
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6.7. Continued Access to Study Intervention After the End of the Study
No study intervention will be provided to participants at the end of their study participation.
6.8. Treatment of Overdose
For this study, any dose of study intervention greater than 1 dose of study intervention within 
a 24-hour time period will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the study medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs as medically appropriate and follow up 
until resolution, stabilization, the event is otherwise explained, or the participant is lost to 
follow-up (as defined in Section 7.3). 
3. Document the quantity of the excess dose as well as the duration of the overdose in the 
CRF.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.
6.9. Prior and Concomitant Therapy
The following concomitant medications and vaccinations will be recorded in the CRF:

Receipt of any COVID-19 vaccine from 12 months prior to enrollment until the last visit 
(Visit 3).

Receipt of licensed or investigational influenza vaccine from 12 months prior to 
enrollment until the last visit (Visit 3).

Any vaccinations received from 28 days prior to Visit 1 until the last visit (Visit 3).

Details of any concomitant medication taken to treat fever or pain (solicited 
reactogenicity symptoms) as reported in the e-diary will be collected.
6.9.1. Prohibited During the Study
Receipt of the following vaccines and medications during the time periods listed below may 
exclude a participant from the per-protocol analysis from that point onward; however, it is 
anticipated that the participant would not be withdrawn from the study (see Section 7). 
Medications should not be withheld if required for a participant’s medical care.

Unless considered medically necessary, no vaccines other than study intervention should 
be administered within 14 days before and 14 days after study vaccination at Visit 1.
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
Receipt of any other (nonstudy) coronavirus vaccine from enrollment throughout the 
entire study is prohibited.

Receipt of any other (nonstudy) seasonal influenza vaccine from enrollment throughout 
the entire study is prohibited.

Receipt of chronic medications with known systemic immunosuppressant effects, or 
radiotherapy, within 60 days before enrollment through conclusion of the study is 
prohibited.

Receipt of systemic corticosteroids (≥20 mg/day of prednisone or equivalent) for 
≥14 days is prohibited from 28 days prior to enrollment through 28 days after 
administration of the study intervention.

Planned receipt of blood/plasma products, immunoglobulins, or monoclonal antibodies, 
from 90 days before study intervention administration through conclusion of the study, is 
prohibited.

Prophylactic antipyretics and other pain medication to prevent symptoms associated with 
study intervention administration are not permitted. However, if a participant is taking a 
medication for another condition, even if it may have antipyretic or pain-relieving 
properties, it should not be withheld prior to study vaccination.
6.9.2. Permitted During the Study

Hormonal contraceptives that meet the requirements of this study are allowed to be used 
in participants who are WOCBP (see Appendix 4).

Medication other than that described as prohibited in Section 6.9.1 required for treatment 
of preexisting conditions or acute illness is permitted.

Inhaled, topical, or localized injections of corticosteroids (eg, intra-articular or intrabursal 
administration) are permitted.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following: AEs; participant 
request; investigator request; pregnancy; protocol deviation (including no longer meeting all 
the inclusion criteria, or meeting 1 or more exclusion criteria).
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Discontinuation of study intervention does not represent withdrawal from the study. If study 
intervention is permanently discontinued, the participant should remain in the study to be 
evaluated for safety. See the SoA for data to be collected at the time of discontinuation of 
study intervention and follow-up for any further evaluations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, further study follow-up, and/or 
future collection of additional information.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at their own request. Reasons for 
discontinuation from the study include the following:

Refused further study procedures;

Lost to follow-up;

Death;

Study terminated by sponsor;

Reactogenicity event;

AEs;

Participant request; 

Investigator request;

Select protocol deviations (eg, receipt of a COVID-19 and influenza vaccine at any time 
during this study).
If a participant withdraws from the study, they may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1)
for disclosure of future information, no further evaluations will be performed and no 
additional data will be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
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7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with them or persons previously authorized by the participant to provide this information. 
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible. The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of study intervention or also from study procedures and/or postvaccination
study follow-up, and entered on the appropriate CRF page. In the event that vital status 
(whether the participant is alive or dead) is being measured, publicly available information 
should be used to determine vital status only as appropriately directed in accordance with 
local law.
7.3. Lost to Follow-Up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return 
for scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to attend a required study visit:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible. Counsel the participant on the importance of maintaining the assigned visit 
schedule, and ascertain whether the participant wishes to and/or should continue in the 
study;

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record;

Should the participant continue to be unreachable, the participant will be considered to 
have withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
8.1. Administrative Procedures
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Age will be collected to critically evaluate the immune response and safety profile by age.
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
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Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that make it unfeasible to perform the 
test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that they have taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study is approximately 
60 mL The actual collection times of blood sampling may change. Additional blood samples 
may be taken for safety assessments at times specified by Pfizer, provided the total volume 
taken during the study does not exceed 550 mL during any period of 56 consecutive days.
8.1.1. Telehealth Visits
Telehealth visits may be used to assess participant safety and collect data points. Telehealth 
includes the exchange of healthcare information and services via telecommunication 
technologies (eg, audio, video, videoconferencing software) remotely, allowing the 
participant and the investigator to communicate on aspects of clinical care, including medical 
advice, reminders, education, and safety monitoring. Assessments that may be performed 
during a telehealth visit are described in the SoA.
Study participants must be reminded to promptly notify site staff about any change in their 
health status.
8.2. Efficacy and/or Immunogenicity Assessments
Samples will be collected at the time points specified in the SoA from all participants and the 
following assays will be performed:

SARS-CoV-2 neutralization assays (Omi XBB.1.5).

HAI titers (from HAI based on cell-derived virus) for the seasonal strains (2×A, 2×B) 
recommended by WHO.
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To describe the immune response to emerging variants of SARS-CoV-2 and/or influenza, 
additional assay may be run on an exploratory basis. 
Virus microneutralization assays may be run on all or a subset of samples on an exploratory 
basis as detailed in the SAP.
8.2.1. Testing for SARS-CoV-2 and Influenza Exposure
The N-binding antibody test will be performed by the central laboratory on each blood 
sample to establish prior exposure to SARS-CoV-2 up to each time point. These data will be 
used for study analyses.
Additional testing to evaluate influenza infection during study participation may be 
performed if assays are available. 
8.2.2. Biological Samples
Blood samples will be used only for scientific research. Each sample will be labeled with a 
code so that the laboratory analyst testing the samples will not know the participant’s 
identity, study visit, or study cohort associated with the sample. Samples that remain after 
performing assays outlined in the protocol may be stored by Pfizer. Unless a time limitation 
is required by local regulations or ethical requirements, the samples will be stored for up to 
15 years after the end of the study and then destroyed. If allowed by the ICD, stored samples 
may be used for additional testing to better understand the immune responses to the 
vaccine(s) under study in this protocol, to inform the development of other vaccines or 
vaccine-related products, and/or for vaccine-related assay work supporting vaccine programs.
No testing of the participant’s DNA will be performed.
The participant may request that their samples, if still identifiable, be destroyed at any time; 
however, any data already collected from those samples will still be used for this research. 
The biological samples may be shared with other researchers as long as confidentiality is 
maintained and no testing of the participant’s DNA is performed.
8.3. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled safety 
measurements may be obtained at any time during the study to assess any perceived safety 
issues.
8.3.1. Physical Examinations
In this study, a physical examination may be performed prior to vaccination, if clinically 
indicated.
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Physical examination findings collected during the study will be considered source record 
and will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.4.1 to 8.4.3.
8.3.2. Vital Signs
For this study, the participant’s oral temperature, pulse rate, and seated blood pressure will be 
measured prior to vaccination. Additionally, weight and height will be measured prior to 
vaccination.
Vital sign findings collected during the study will be considered source record and will not be 
required to be reported, unless otherwise noted.
Any untoward vital sign findings that are identified during the active collection period and 
meet the definition of an AE or SAE (Appendix 3) must be reported according to the 
processes in Sections 8.4.1 to 8.4.3.
8.3.3. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study. 
8.3.4. Electronic Diary
All participants will be required to complete a reactogenicity e-diary after vaccination given 
at Visit 1, through an application installed on a provisioned device or on the participant’s 
own personal device. All participants will be asked to monitor and record local reactions, 
systemic events, and use of any medication for solicited pain symptoms or fever for 7 days, 
or longer for ongoing symptoms, from the day of administration of the study intervention 
given at Visit 1. The reactogenicity e-diary allows recording of these assessments each day, 
thus providing the accurate representation of the participant’s experience. Data on local 
reactions and systemic events reported in the reactogenicity e-diary will be transferred 
electronically to a third-party vendor, where they will be available for review by investigators 
and the Pfizer clinicians at all times via an internet-based portal.
At intervals agreed to by the vendor and Pfizer, these data will be transferred electronically 
into Pfizer’s database for analysis and reporting. Generally, these data do not need to be 
reported by the investigator in the CRF as AEs. However, if a participant has a serious 
adverse event reported in the e-diary, the event(s) should be recorded on the CRF, regardless 
of whether the investigator considers the event(s) to be related. If a participant missed 
reporting an event in the e-diary and reports it to the study site instead, the event should also 
be recorded on the CRF.
Investigators (or designee) will be required to review the reactogenicity e-diary data online at 
frequent intervals to evaluate participant compliance and as part of the ongoing safety review.
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The investigator or designee must obtain stop dates from the participant for any symptoms 
ongoing on the last day from Day 7 onwards and follow up daily until resolution. The stop 
dates should be documented in the source documents and the information entered in the CRF.
8.3.4.1. Grading Scales
The grading scales used in this study to assess local reactions and systemic events as 
described below are derived from the FDA CBER guidelines on toxicity grading scales for 
healthy adult volunteers enrolled in preventive vaccine clinical trials.37
8.3.4.2. Local Reactions
During the reactogenicity e-diary reporting period, participants will be asked to assess 
redness, swelling, and pain at each injection site and to record the symptoms in the 
reactogenicity e-diary. 
If a local reaction persists beyond the end of the 7-day e-diary collection period following 
vaccination, the participant will be requested to report that information and/or any new 
reactogenicity reactions that develop to the investigator or the study staff. The investigator 
will enter this additional information in the CRF.
Participants will be provided with a measuring device. Redness and swelling will be 
measured and recorded in measuring device units (range: 1 to 21) and then categorized 
during analysis as absent, mild, moderate, or severe based on the grading scale in Table 4. 
Measuring device units can be converted to centimeters according to the following formula: 
1 measuring device unit = 0.5 cm. Pain at the injection site will be assessed by the participant 
as absent, mild, moderate, or severe according to the grading scale in Table 4.
If a Grade 3 local reaction is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated. Only an investigator or medically qualified person is able to classify a participant’s 
local reaction as Grade 4. If a participant experiences a confirmed Grade 4 local reaction, the 
investigator must immediately notify the sponsor.
Table 4.
Local Reaction Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4)
Pain at the 
injection site
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain
Redness
2.0 cm to 5.0 cm
(5 to 10 measuring 
device units)
5.0 cm to 10.0 cm 
(11 to 
20 measuring 
device units)
10 cm 
(≥21 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
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Table 4.
Local Reaction Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4)
Swelling
2.0 cm to 5.0 cm
(5 to 10 measuring 
device units)
5.0 cm to 10.0 cm 
(11 to 
20 measuring 
device units)
10 cm 
(≥21 measuring 
device units)
Necrosis
8.3.4.3. Systemic Events
During the reactogenicity e-diary reporting period, participants will be asked to assess 
vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain, and new or 
worsened joint pain and to record the symptoms in the reactogenicity e-diary. The symptoms 
will be assessed by the participant as absent, mild, moderate, or severe according to the 
grading scale in Table 5.
If a systemic event persists beyond the end of the 7-day e-diary collection period following 
vaccination, the participant will be requested to report that information and/or any new 
reactogenicity events that develop to the investigator or the study staff. The investigator will 
enter this additional information in the CRF. If a Grade 3 systemic event is reported in the 
reactogenicity e-diary, a telephone contact should occur to ascertain further details and 
determine whether a site visit is clinically indicated. Only an investigator or medically 
qualified person is able to classify a participant’s systemic event as Grade 4. If a participant 
experiences a confirmed Grade 4 systemic event, the investigator must immediately notify 
the sponsor. A Grade 4 systemic event will be collected on the CRF.
Table 5.
Systemic Event Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4)
Vomiting
1-2 times in 24 
hours
2 times in 24 
hours
Requires IV 
hydration
Emergency room 
visit or 
hospitalization for 
hypotensive shock
Diarrhea
2 to 3 loose stools 
in 24 hours
4 to 5 loose stools 
in 24 hours
6 or more loose 
stools in 24 hours
Emergency room 
visit or 
hospitalization for 
severe diarrhea
Headache
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe headache
Fatigue/tiredness
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe fatigue
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Table 5.
Systemic Event Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4)
Chills
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe chills
New or worsened 
muscle pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe new or 
worsened muscle 
pain
New or worsened 
joint pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily 
routine activity
Emergency room 
visit or 
hospitalization for 
severe new or 
worsened joint pain
8.3.4.4. Fever
In order to record information on fever, a thermometer will be given to participants with 
instructions on how to measure oral temperature at home. Temperature will be collected in 
the reactogenicity e-diary daily for 7 days or longer following vaccination (where Day 1 is 
the day of vaccination). It will also be collected at any time during the reactogenicity e-diary 
data collection periods when fever is suspected. Fever is defined as an oral temperature 
≥38.0°C (≥100.4°F). The highest temperature for each day will be recorded in the 
reactogenicity e-diary. Temperature will be measured and recorded to 1 decimal place. 
Temperatures recorded in degrees Fahrenheit will be programmatically converted to degrees 
Celsius and then categorized according to the scale shown in Table 6 during analysis.
If a fever of ≥39.0°C (≥102.1°F) is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated. Only an investigator or medically qualified person is able to confirm a 
participant’s fever as >40.0°C (>104.0°F). If a participant experiences a confirmed fever 
>40.0°C (>104.0°F), the investigator must immediately notify the sponsor. Fevers >40.0°C 
(>104.0°F) will be collected on the CRF.
Table 6.
Scale for Fever
≥38.0-38.4°C (100.4-101.1°F)
>38.4-38.9°C (101.2-102.0°F)
>38.9-40.0°C (102.1-104.0°F)
>40.0°C (>104.0°F)
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8.3.4.5. Antipyretic Medication
The use of antipyretic medications to treat pain symptoms or fever associated with study 
intervention administration will be recorded in the reactogenicity e-diary daily during the 
7-day reporting period or longer for ongoing symptoms.
8.3.5. Phase 1 Stopping Rules
The following stopping rules are in place for all Phase 1 participants, based on review of AE 
data and e-diary reactogenicity data, until the start of Phase 2 or 30 days after the 
administration of the last dose of study intervention in Phase 1, whichever is later. These data 
will be monitored on an ongoing basis by the investigator (or medically qualified designee) 
and sponsor in order to promptly identify and flag any event that potentially contributes to a 
stopping rule.
The sponsor study team will be unblinded so will be able to assess whether or not a stopping 
rule has been met on the basis of a participant’s individual study intervention allocation.
In the event that sponsor personnel confirm that a stopping rule is met, the following actions 
will commence:

The IRC will review all appropriate data.

The stopping rule will PAUSE randomization and study intervention administration for 
the impacted vaccine group.

For all participants vaccinated, all other routine study conduct activities, including 
ongoing data entry, reporting of AEs, participant reactogenicity e-diary completion, 
blood sample collection, and participant follow-up, will continue during the pause.
A stopping rule is met if any of the following rules occur after the administration of study 
intervention. Reactogenicity e-diary data confirmed by the investigator as being entered by 
the participant in error will not contribute toward a stopping rule. Once the IRC have 
reviewed the safety data and provided guidance, a notification will be sent from the sponsor 
to the sites with guidance on how to proceed.
Stopping Rule Criteria for Each Vaccine Group:

If any vaccinated participant develops an SAE that is assessed by the investigator as 
possibly related to the study intervention, or for which there is no alternative, plausible, 
attributable cause.

If any participant develops a Grade 4 local reaction or systemic event after vaccination 
(see Section 8.3.4) that is assessed as possibly related by the investigator, or for which 
there is no alternative, plausible, attributable cause.
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
If any participant develops a fever >40°C (>104.0°F) for at least 1 daily measurement 
after vaccination (see Section 8.3.4.4) that is assessed as possibly related by the 
investigator, or for which there is no alternative, plausible, attributable cause. 

If any vaccinated participant develops confirmed myocarditis or pericarditis.

If any vaccinated participant dies.

If any vaccinated participant experiences a Grade 4 unsolicited AE, or SAE of any 
severity, assessed as related to the study intervention by the investigator.

If any 2 participants vaccinated participants develop the same or similar Grade 3 or 
higher unsolicited AE, other than myocarditis/pericarditis, assessed as related to study 
intervention by the investigator. Note that the solicited local reactions, systemic events, 
and fever specified in Section 8.3.4, reported within 7 days from the day of 
administration of the study intervention, irrespective of whether they are recorded in the 
e-diary or as AEs, are excluded from this stopping rule.
8.3.6. Pregnancy Testing 
Following screening, pregnancy tests may be urine or serum tests, but must have a sensitivity 
of at least 25 mIU/mL. Pregnancy tests will be performed in WOCBP at the times listed in 
the SoA, immediately before the administration of each dose of study intervention. A 
negative pregnancy test result will be required prior to receiving the study intervention. 
Pregnancy tests may also be repeated if requested by IRBs/ECs or if required by local 
regulations. In the case of a positive confirmed pregnancy, the participant will be withdrawn 
from administration of study intervention but may remain in the study.
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study (see Section 7.1). 
During the active collection period as described in Section 8.4.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.
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In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.4.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including 
Visit 2. At Visit 3 (approximately 6 months after vaccination), the participant will be asked 
about AESIs since Visit 1.
Additionally, any AEs occurring up to 48 hours after any subsequent blood draws must be 
recorded in the CRF.
SAEs will be collected from the time the participant provides informed consent through the 
duration of the study (Visit 3, approximately 6 months after vaccination).
Follow-up by the investigator continues throughout the active collection period and until the 
AE or SAE or its sequelae resolve or stabilize at a level acceptable to the investigator.
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues until the AE or SAE or its sequelae resolve or 
stabilize at a level acceptable to the investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant permanently discontinues or temporarily discontinues from the study because 
of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE reported using 
the Vaccine SAE Report Form or via PSSA.
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has concluded study participation, and they 
consider the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the Vaccine SAE Report Form or via PSSA.
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8.4.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in
Section 8.4.1 are reported to Pfizer Safety on the Vaccine SAE Report Form/PSSA
immediately upon awareness and under no circumstance should this exceed 24 hours, as 
indicated in Appendix 3. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of its being available.
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.4.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
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.
8.4.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.4.3. Follow-Up of AEs and SAEs
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is provided in Appendix 3.
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8.4.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.4.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure.
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.4.5.1. Exposure During Pregnancy
An EDP occurs if:

A female participant is found to be pregnant while receiving or after discontinuing study 
intervention.

A male participant who is receiving or has discontinued study intervention inseminates a 
female partner.

A female nonparticipant is found to be pregnant while being exposed or having been 
exposed to study intervention because of environmental exposure. Below are examples of 
environmental EDP:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by inhalation or skin contact.
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
A male family member or healthcare provider who has been exposed to the study 
intervention by inhalation or skin contact then inseminates his female partner prior to 
or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 

If EDP occurs in a participant/participant’s partner, the investigator must report this 
information to Pfizer Safety using the Vaccine SAE Report Form and an EDP 
Supplemental Form or via PSSA, regardless of whether an SAE has occurred. Details of 
the pregnancy will be collected after the start of study intervention and until 28 days after 
study intervention.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the Vaccine SAE Report Form and an EDP 
Supplemental Form or via PSSA. Since the exposure information does not pertain to the 
participant enrolled in the study, the information is not recorded on a CRF; however, a 
copy of the completed report is maintained in the investigator site file.

Follow-up is conducted to obtain general information on the pregnancy and its outcome 
for all EDP reports with an unknown outcome. The investigator will follow the 
pregnancy until completion (or until pregnancy termination) and notify Pfizer Safety of 
the outcome as a follow-up to the initial report. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, 
the reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion should be reported as an 
SAE;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs. In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the study intervention. 
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Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.5.2. Exposure During Breastfeeding
An EDB occurs if:

A female participant is found to be breastfeeding while receiving or after discontinuing 
study intervention.

A female nonparticipant is found to be breastfeeding while being exposed or having been 
exposed to study intervention (ie, environmental exposure). An example of 
environmental EDB is a female family member or healthcare provider who reports that 
she is breastfeeding after having been exposed to the study intervention by inhalation or 
skin contact.  
The investigator must report EDB to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The information must be reported 
using the Vaccine SAE Report Form or via PSSA. When EDB occurs in the setting of 
environmental exposure, the exposure information does not pertain to the participant enrolled 
in the study, so the information is not recorded on a CRF. However, a copy of the completed
report is maintained in the investigator site file.
An EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accordance with authorized use. 
However, if the infant experiences an SAE associated with such a drug, the SAE is reported 
together with the EDB.
8.4.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the Vaccine SAE Report Form or via PSSA, 
regardless of whether there is an associated SAE. Since the information about the 
occupational exposure does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed report is maintained in the 
investigator site file.
8.4.6. Cardiovascular and Death Events
Deaths and cardiovascular events will be recorded throughout the study as detailed in
Section 8.4.1.
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8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.4.8. Adverse Events of Special Interest
The following events are protocol-specified AESIs:

Confirmed COVID-19 diagnosis (clinical signs/symptoms and positive SARS-CoV-2 
NAAT or antigen test) after Visit 1 through the end of the study.

Confirmed diagnosis of myocarditis or pericarditis occurring after vaccination. See
Section 8.10.5.

Potential menstrual cycle disturbances. See Section 8.10.6.

GBS.

Neuritis, including Bell’s palsy.

Vasculitis.
AESIs are examined as part of routine safety data review procedures throughout the clinical 
trial and as part of signal detection processes. Should an aggregate analysis indicate that 
these prespecified events occur more frequently than expected, eg, based on epidemiological 
data, literature, or other data, then this will be submitted and reported in accordance with 
Pfizer’s safety reporting requirements. Aggregate analyses of safety data will be performed 
on a regular basis per internal SOPs.
All AESIs must be reported as an AE or SAE following the procedures described in 
Section 8.4.1 through Section 8.4.4. An AESI is to be recorded as an AE or SAE on the CRF. 
In addition, an AESI that is also an SAE must be reported using Vaccine SAE Report Form
or via PSSA.
8.4.8.1. Lack of Efficacy
The investigator must report signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy. Lack of efficacy or failure of expected pharmacological action is reportable to Pfizer 
Safety only if associated with an SAE.  
8.4.9. Medical Device Deficiencies
Medical devices being provided for use in this study are those listed in Section 6.1.2. In order 
to fulfill regulatory reporting obligations worldwide, the unblinded site staff is responsible 
for the detection and documentation of events meeting the definitions of device deficiency
that occur during the study with such devices.
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The definition of a medical device deficiency can be found in Appendix 7.
Note: AEs and/or SAEs that are associated with a medical device deficiency will follow the 
same processes as other AEs or SAEs, as outlined in Sections 8.4.1 through 8.4.4 and
Appendix 3 of the protocol.
8.4.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies that result in an incident will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
Importantly, reportable device deficiencies are not limited to problems with the device itself 
but also include incorrect or improper use of the device and even intentional misuse, etc. 
If the unblinded site staff learns of any device deficiency at any time after a participant has 
been discharged from the study, and such deficiency is considered reasonably related to a 
medical device provided for the study, the unblinded site staff will promptly notify the 
sponsor.
Refer to Section 10.7.4 for instructions for documenting and reporting medical device 
deficiencies. 
8.4.9.2. Follow-Up of Medical Device Deficiencies
Follow-up applies to all participants, including those who discontinue study intervention.
The unblinded site staff are responsible for ensuring that follow-up includes any 
supplemental investigations as indicated to elucidate the nature and/or causality of the 
deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the unblinded site staff.
8.4.9.3. Regulatory Reporting Requirements for Device Deficiencies
The unblinded site staff will promptly report all device deficiencies occurring with any 
medical device provided for use in the study in order for the sponsor to fulfill the legal 
responsibility to notify appropriate regulatory authorities and other entities about certain 
safety information relating to medical devices being used in clinical studies.
The unblinded site staff, or responsible person according to local requirements (eg, the head 
of the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB/EC.
Note: There are additional reporting obligations for medical device deficiencies that are 
potentially related to SAEs (ie, an SADE) that must fulfill the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety information relating 
to medical devices being used in clinical studies.
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
Any device deficiency that is associated with an SAE must be reported to the sponsor 
within 24 hours after the investigator determines that the event meets the definition of a 
device deficiency.

The sponsor shall review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These shall be reported to the regulatory 
authorities and IRBs/ECs as required by national regulations.
8.4.10. Vaccination Errors
Vaccination errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Vaccination errors are recorded and reported as follows:
Recorded on the 
Medication Error Page 
of the CRF
Recorded on the 
Adverse Event Page 
of the CRF
Reported on the Vaccine 
SAE Report Form/PSSA
to Pfizer Safety Within 
24 Hours of Awareness
All (regardless of whether 
associated with an AE)
Any AE or SAE associated 
with the vaccination error
Only if associated with an 
SAE
Vaccination errors include:

Vaccination errors involving participant exposure to the study intervention;

Potential vaccination errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;

The administration of expired study intervention;

The administration of an incorrect study intervention;

The administration of an incorrect dosage;

The administration of study intervention that has undergone temperature excursion from 
the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use.

The administration of the prepared combined vaccine after more than 4 hours of 
storage at 25°C. 
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Whether or not the vaccination error is accompanied by an AE, as determined by the 
investigator, such vaccination errors occurring to a study participant are recorded on the 
medication error page of the CRF, which is a specific version of the AE page and, if 
applicable, any associated serious and nonserious AE(s) are recorded on the AE page of the 
CRF.
In the event of a vaccination dosing error, the sponsor should be notified within 24 hours.
Vaccination errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Report Form or via PSSA only when associated with an SAE.
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. Genetics
Not applicable.
8.7. Biomarkers
Biomarkers are not evaluated in this study.
8.8. Immunogenicity Assessments
Refer to Section 8.2. 
8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.10. Study Procedures
8.10.1. 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 participant. Each signature on the 
ICD must be personally dated by the signatory. The investigator or his or her designee will 
also sign the ICD. A copy of the signed and dated ICD must be given to the participant. 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.

Assign a single participant number using the IRT system.

Obtain the participant’s demography (including age in years, sex, race, and ethnicity).

Obtain medical history and any other medical history of clinical significance.
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On the day of and prior to study intervention administration, perform a clinical 
assessment. If the clinical assessment indicates that a physical examination is necessary 
to comprehensively evaluate the participant, perform a physical examination and record 
any findings in the source documents and, if clinically significant, record findings on the 
medical history CRF.

Measure the participant’s height and weight.

On the day of and prior to study intervention administration, measure the participant’s 
oral temperature and seated blood pressure. 

Record nonstudy vaccinations and prior receipt of any licensed or investigational 
COVID-19 or influenza vaccine as described in Section 6.9.

On the day of and prior to study intervention administration, perform a urine pregnancy 
test on WOCBP as described in Section 8.3.6.

If applicable, discuss contraceptive use as described in Section 10.4.4.

On the day of and prior to study intervention administration, ensure and document that all 
of the inclusion criteria and none of the exclusion criteria are met.

On the day of and prior to study intervention administration, ensure that the participant 
meets none of the temporary delay criteria as described in Section 5.5.

On the day of and prior to study intervention administration, obtain the participant’s 
randomization number and study intervention allocation using the IRT system.

On the day of and prior to study intervention administration, collect a blood sample 
(approximately 20 mL), before administration of study intervention, for immunogenicity 
assessment.

Site staff member(s) will dispense/administer 2 injections (1 in each arm) into the deltoid 
muscle of the prescribed arm based on the study intervention allocation as detailed in
Table 3. Please refer to the IPM for further instruction on this process.

Site staff must observe the participant for at least 30 minutes after study intervention 
administration for any acute reactions. Record any acute reactions (including time of 
onset) in the participant’s source documents, on the CRF, and on an SAE form as 
applicable.

Explain the e-diary technologies available for this study (see Section 8.3.4), and assist the 
participant in downloading the study application onto the participant’s own device or 
issue a provisioned device if required.
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Provide instructions on reactogenicity e diary completion and ask the participant to 
complete the reactogenicity e-diary from Day 1 through Day 7 or longer until any 
symptoms that are ongoing are resolved, with Day 1 being the day of vaccination.

Issue a measuring device to measure local reactions at the injection site and a 
thermometer for recording daily temperatures; provide instructions on their use.

Ask the participant to contact the site staff or investigator immediately if the 
participant experiences any of the following from Day 1 through Day 7 after 
vaccination (where Day 1 is the day of vaccination) to determine if an unscheduled 
reactogenicity visit is required:

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring greater than 10 cm 
(20 measuring device units).

Severe pain at the injection site.

Any severe systemic event.

Record AEs as described in Section 10.3.

Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.10.5).

Schedule an appointment for the participant to return for the next study visit.

Remind the participant to bring the e-diary to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs and a
dispenser/administrator updates the study intervention accountability records.

The investigator or appropriately qualified designee reviews the reactogenicity
e-diary data online and records the assessment in the CRF following vaccination to 
evaluate participant compliance and as part of the ongoing safety review. Daily review is 
optimal during the active diary period.
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8.10.2. Visit 2 – 4-Week Follow-Up Visit (After Vaccination) – 28 to 35 Days After 
Visit 1

Record AEs as described in Section 8.4.

Record nonstudy vaccinations as described in Section 6.9.

If applicable, discuss contraceptive use as described in Section 10.4.4.

Collect a blood sample of approximately 20 mL for immunogenicity testing.

Review the participant’s reactogenicity e-diary data and record assessment in the CRF. 
Assess compliance, record any medically attended events (including hospitalizations), 
and collect stop dates for any symptoms/medications ongoing on the last day of the 
e-diary collection period in the CRF. For symptoms still ongoing, continue to follow up 
until resolution, and document and record stop dates in the CRF.

Record reactogenicity medication used as described in Section 8.3.4.

Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Collect the participant’s e-diary or assist the participant with removing the study 
application from his or her own personal device.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

Record any AEs that occur within the 48 hours after the blood draw as described in
Section 8.4.
8.10.3. Visit 3 – 6-Month Follow-Up Visit (After Vaccination) – 175 to 189 Days After 
Visit 1

Record SAEs and AESIs as described in Section 8.4.

Record nonstudy vaccinations as described in Section 6.9.

Collect a blood sample of approximately 20 mL for immunogenicity testing.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

Record any AEs that occur within the 48 hours after the blood draw as described in
Section 8.4.
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8.10.4. Unscheduled Visit for a Grade 3 or Suspected Grade 4 Reaction
If a Grade 3 local reaction (Section 8.3.4.2), systemic event (Section 8.3.4.3), or fever 
(Section 8.3.4.4) is reported in the reactogenicity e-diary, a telephone contact should occur to 
ascertain further details and determine whether a site visit is clinically indicated. If a 
suspected Grade 4 local reaction (Section 8.3.4.2), systemic event (Section 8.3.4.3), or fever 
(Section 8.3.4.4) is reported in the reactogenicity e-diary, a telephone contact or site visit 
should occur to confirm whether the event meets Grade 4 criteria.
A site visit must be scheduled as soon as possible to assess the participant unless any of the 
following is true:

The participant is unable to attend the unscheduled visit.

The local reaction/systemic event is no longer present at the time of the telephone 
contact.

The participant recorded an incorrect value in the reactogenicity e-diary (confirmation of 
a reactogenicity e-diary data entry error).

The PI or authorized designee determined it was not needed.
This telephone contact will be recorded in the participant’s source documentation and the 
CRF.
If the participant is unable to attend the unscheduled visit, or the PI or authorized designee 
determined it was not needed, any ongoing local reactions/systemic events must be followed
daily until resolution.
During the unscheduled visit, the reactions should be assessed by the investigator or a 
medically qualified member of the study staff, such as a study physician or a study nurse, as 
applicable to the investigator’s local practice, who will:

Measure oral temperature (°F/°C).

Measure minimum and maximum diameters of redness (if present).

Measure minimum and maximum diameters of swelling (if present).

Assess injection site pain (if present) in accordance with the grades provided in
Section 8.3.4.2.

Assess systemic events (if present) in accordance with the grades provided in
Section 8.3.4.3.

Assess for other findings associated with the reaction and record these on the CRF if 
appropriate.
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The investigator or an authorized designee will complete the unscheduled visit assessment 
page of the CRF.
8.10.5. Additional Procedures for Monitoring of Potential Myocarditis or Pericarditis
Any study participant who reports the following within 28 days after the study vaccination 
should be specifically evaluated, preferably by a cardiologist, for possible myocarditis or 
pericarditis: 

Acute chest pain, 

Shortness of breath, 

Palpitations, or 

Any other symptom(s) that might be indicative of myocarditis or pericarditis.
In addition to a clinical evaluation, the following should be performed:

ECG and

Measurement of the troponin level.
If myocarditis or pericarditis is suspected based upon the initial evaluation, the following 
should also be performed:

Cardiac echocardiogram and/or

Cardiac magnetic resonance study.

Details of the symptoms reported, and results of the investigations performed, will be 
recorded in the CRF. Any diagnosis made (myocarditis, pericarditis, or other) should be 
recorded as an SAE. Refer also to Section 8.4.8.
8.10.6. Additional Procedures for Monitoring of Potential Menstrual Cycle 
Disturbances
Any female study participant who reports any symptoms that may indicate a disturbance of 
their normal menstrual cycle (including, but not exclusively, heavy menstrual bleeding, 
amenorrhea, irregular periods) following receipt of study intervention until 6 months after the 
last vaccination should be specifically evaluated by the investigator. Details of the symptoms, 
menstrual history, and results of any investigations performed will be recorded in the CRF.
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9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in the SAP, which will be maintained by the sponsor. The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
There is no formal hypothesis testing. All statistical analyses will be descriptive.
9.1.1. Estimands
The estimands corresponding to the primary objectives are described in the table in 
Section 3.
The safety primary objective evaluations are based on the safety population. In general, 
completely missing reactogenicity data (ie, all 7 days of collection were missing) will not be 
imputed. For partially missed reactogenicity data (eg, 1-6 days of reactogenicity data are 
available), it is assumed that no reactions or events were experienced on the missing days. 
Missing AE start dates will be imputed according to Pfizer safety rules. No other missing 
information will be imputed in the safety analysis.
The estimands to evaluate the immunogenicity objective are based on the evaluable 
immunogenicity population (Section 9.2). These estimands estimate the vaccine effect in the 
hypothetical setting where participants follow the study schedules and protocol requirements 
as directed. Missing antibody results will not be imputed. Immunogenicity results that are 
below the LLOQ will be set to 0.5 × LLOQ in the analysis. This may be adjusted once 
additional data on the assay characteristics become available.
9.1.2. Multiplicity Adjustment
No multiplicity adjustment is needed for the study as there is no statistical hypothesis.
9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set
Description
Screened
All participants who have a signed ICD.
Randomized
All participants who are assigned a randomization number in 
the IRT system.
Safety 
All participants who receive at least 1 dose of the study 
intervention.
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Participant Analysis Set
Description
Evaluable immunogenicity
All eligible assigned participants who receive the study 
intervention to which they are assigned, have at least 1 valid 
and determinate immunogenicity result from the blood 
sample collected within an appropriate window, and have no 
other important protocol deviations as determined by the 
clinician.
All-available 
immunogenicity
All assigned participants who receive the study intervention 
and have 1 valid and determinate immunogenicity result after 
vaccination.
9.3. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data.
This section is a summary of the planned statistical analyses of the primary and exploratory
endpoints.
9.3.1. General Considerations
Other than IRC review of early Phase 1 safety data before initiation of Phase 2 enrollment, 
data from Phase 1 and Phase 2 participants will be combined for the safety and 
immunogenicity analyses.
CIs for all endpoints in the statistical analysis will be presented as 2-sided at the 95% level 
unless specified otherwise.
The safety analyses are based on the safety population. Participants will be summarized by 
vaccine group according to the study interventions they actually received.
For all the immunogenicity endpoints, the analysis will be based on the evaluable 
immunogenicity population. An additional analysis may be performed based on the 
all-available immunogenicity population if there is a large enough difference in sample size 
between the all-available immunogenicity population and the evaluable immunogenicity 
population. Participants will be summarized according to the vaccine group to which they 
were randomized.
9.3.1.1. Analysis for Binary Data
Descriptive statistics for categorical variables (eg, proportions) are the percentage (%), the 
numerator (n) and the denominator (N) used in the percentage calculation, and the 95% CIs, 
where applicable.
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The exact 95% CI for binary endpoints for each group will be computed using the 
F distribution (Clopper-Pearson).40 The 95% CI for the between-group difference for binary 
endpoints will be calculated using the Miettinen and Nurminen method.
9.3.1.2. Analysis for Continuous Data
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
standard deviation, minimum, and maximum.
9.3.1.2.1. Geometric Means
The geometric means will be calculated as the mean of the assay results after making the 
logarithm transformation and then exponentiating the mean to express results on the original 
scale. Two-sided 95% CIs will be obtained by taking log transformations of assay results, 
calculating the 95% CI with reference to the Student t distribution, and then exponentiating 
the confidence limits.
9.3.1.2.2. Geometric Mean Ratios
Model-Based GMR:
The GMR and associated 95% CI will be calculated by exponentiating the difference in LS 
means and the corresponding CIs based on analysis of logarithmically transformed assay 
results using a linear regression model that includes terms for baseline assay results
(log scale), age, and comparison group.
Unadjusted GMR:
The GMR will be calculated as the mean of the difference of logarithmically transformed 
assay results and exponentiating the mean. Two-sided CIs will be obtained by calculating CIs 
using the Student t distribution for the mean difference of the logarithmically transformed 
assay results and exponentiating the confidence limits.
9.3.1.2.3. Geometric Mean Fold Rises
GMFRs are defined as ratios of the results after vaccination to the results before vaccination. 
GMFRs are limited to participants with nonmissing values at both time points. GMFRs will 
be calculated as the mean of the difference of logarithmically transformed assay results (later 
time point minus earlier time point) and exponentiating the mean. The associated 2-sided 
95% CIs will be obtained by constructing CIs using the Student t distribution for the mean 
difference on the logarithm scale and exponentiating the confidence limits.
9.3.1.2.4. Reverse Cumulative Distribution Curves
Empirical RCDCs will plot proportions of participants with values equal to or exceeding a 
specified assay value versus the indicated assay value, for all observed assay values. Data 
points will be joined by a step function with data points on the left side of the step.
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9.3.2. Primary Endpoint(s)/Estimand(s) Analysis
Endpoint
Statistical Analysis Methods
Safety
Descriptive statistics will be provided for each reactogenicity endpoint
for each vaccine group. Local reactions and systemic events from Day 1 
through Day 7 after vaccination (where Day 1 is the day of vaccination) 
will be presented by severity and cumulatively across severity levels. 
Descriptive summary statistics will include counts and percentages of 
participants with the indicated endpoint and the associated 
Clopper-Pearson 95% CIs.
AEs and SAEs will be categorized according to MedDRA terms. 
Counts, percentages, and associated Clopper-Pearson 95% CIs of AEs 
from vaccination through 4 weeks and SAEs from vaccination through 
6 months after vaccination will be provided for each vaccine group.
Immunogenicity

GMTs and 2-sided 95% CIs of SARS-CoV-2 Omicron
(XBB.1.5)–neutralizing titers and strain-specific HAI titers (for the 
seasonal strains recommended by WHO) before vaccination and at 
4 weeks after vaccination will be provided for each vaccine group. 
Statistical methods are described in Section 9.3.1.2.1.

GMFRs of SARS-CoV-2 Omicron (XBB.1.5)–neutralizing titers and 
strain-specific HAI titers (for the seasonal strains recommended by 
WHO) from before vaccination to 4 weeks after study vaccination, 
along with the associated 2-sided 95% CIs, will be provided for each 
vaccine group. Statistical methods are described in Section 9.3.1.2.3.

The percentages of participants with seroresponse to SARS-CoV-2 
Omicron (XBB.1.5) at 4 weeks after vaccination, the percentages of 
participants with HAI seroconversion at 4 weeks after vaccination, 
and percentages of participants with HAI titers ≥1:40 before 
vaccination and at 4 weeks after vaccination and the associated 
Clopper-Pearson 95% CIs will be provided for each vaccine group.
9.3.3. Secondary Endpoint(s)/Estimand(s) Analysis
Not applicable.
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9.3.4. Tertiary/Exploratory Endpoint(s) Analysis
Immunogenicity

GMTs and 2-sided 95% CIs of SARS-CoV-2 Omicron 
(XBB.1.5)–neutralizing titers and strain-specific HAI titers (for the 
seasonal strains recommended by WHO) before vaccination and at 
6 months after vaccination will be provided for each vaccine group. 
Statistical methods are described in Section 9.3.1.2.1.

GMFRs of SARS-CoV-2 Omicron (XBB.1.5)–neutralizing titers 
and strain-specific HAI titers (for the seasonal strains 
recommended by WHO) from before vaccination to 6 months after 
study vaccination, along with the associated 2-sided 95% CIs, will 
be provided for each vaccine group. Statistical methods are 
described in Section 9.3.1.2.3.

The percentages of participants with seroresponse to SARS-CoV-2 
Omicron (XBB.1.5) at 6 months after vaccination, the percentages 
of participants with HAI seroconversion at 6 months after 
vaccination, and percentages of participants with HAI titers ≥1:40 
before vaccination and at 6 months after vaccination and the 
associated Clopper-Pearson 95% CIs will be provided for each 
vaccine group.
Immune response 
to emerging 
variants

For SARS-CoV-2-neutralizing titers and/or HAI titers for emerging 
variants (under monitoring, of interest, and/or of concern), GMTs, 
GMFRs, percentages of participants with seroresponse, and 
percentages of participants with seroconversion or HAI titers ≥1:40
at the specific time point, along with the associated 95% CIs, will 
be summarized in the same way as for the immunogenicity primary 
endpoints described above. This analysis may be conducted in a 
selected subset of participants.
Descriptive 
comparison of 
immune response

GMRs and the differences in percentages of participants with 
seroresponse to SARS-CoV-2 Omicron (XBB.1.5) and with HAI 
seroconversion between certain groups of interest will be calculated 
along with the associated 2-sided 95% CIs.
HAI titers by virus 
microneutralization 
assay

For HAI titers measured by virus microneutralization assays, 
GMTs, GMFRs, and percentages of participants with 
seroconversion or HAI titers ≥1:40 at the specific time point, along 
with the associated 95% CIs, will be summarized in the same way 
as for the immunogenicity primary endpoints described above. This 
analysis may be conducted in a selected subset of participants.
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9.4. Interim Analyses
No interim analysis will be conducted for this study. As this is a sponsor–open-label study,
Pfizer may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment and/or supporting clinical development. Statistical analyses will 
be carried out when the final data for specified objectives are available while the study is 
ongoing. The timing of these planned analysis and reporting events is described in 
Section 9.4.1.
9.4.1. Analysis Timing
Statistical analyses will be carried out when the following data are available:

Safety and immunogenicity data through 4 weeks after vaccination.

Safety and immunogenicity data through 6 months after vaccination.
Additional analyses may be conducted if required for regulatory purposes, to inform product 
development, and/or for program-level decisions. Certain analyses may be combined as 
1 regulatory submission report if the data become available around the same time.
9.5. Sample Size Determination
The sample size is not based on any formal hypothesis test. All statistical analyses will be 
descriptive.
For safety outcomes, Table 7 shows the probability of observing at least 1 AE for a given 
true event rate of a particular AE. For example, if the true AE rate is 1%, with approximately 
160 participants in a vaccine group, there is 80% probability of observing at least 1 AE.
Table 7.
Probability of Observing at Least 1 AE, by Assumed True Event Rate
Assumed True Event Rate of an 
AE
N=20
N=80
N=160
N=640
0.1%
0.02
0.08
0.15
0.47
0.5%
0.10
0.33
0.55
0.96
1%
0.18
0.55
0.80
0.99
2%
0.33
0.80
0.96
0.99
3%
0.46
0.91
0.99
0.99
4%
0.56
0.96
0.99
0.99
5%
0.64
0.98
0.99
0.99
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 536/2014 for clinical 
studies, European MDR 2017/745 for clinical device research, and all other applicable 
local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participant and answer all questions regarding the 
study. The participant should be given sufficient time and opportunity to ask questions and to 
decide whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each participant is fully informed about the nature and 
objectives of the study, the sharing of data related to the study, and possible risks associated 
with participation, including the risks associated with the processing of the participant’s 
personal data. 
The participant must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about their
right to access and correct their personal data and to withdraw consent for the processing of 
their personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.
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Participants must be reconsented to the most current version of the IRB/EC-approved ICD(s) 
during their participation in the study as required per local regulations.
A copy of the ICD(s) must be provided to the participant.
Participants who are rescreened are required to sign a new ICD.
10.1.3.1. Electronic Consent
Participants may be able to experience the informed consent process by electronic means 
(eConsent). The eConsent process includes an electronic presentation of the informed 
consent document (eICD), clinical trial educational components (as applicable), and
electronic signatures (if allowed by local regulations). The use of eConsent does not replace 
or alter the ICD content or informed consent process as described above. The eConsent 
process complies with applicable regulations and sponsor policies to ensure reliability and 
data privacy. 
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to their actual identity and medical record ID. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access.
The sponsor maintains SOPs on how to respond in the event of unauthorized access, use, or 
disclosure of sponsor information or systems.
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10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee 
This study will use an IRC. The IRC is independent of the study team and includes only 
internal members. The IRC charter describes the role of the IRC in more detail.
The IRC will be responsible for ongoing monitoring of the safety of participants in the study 
according to the charter. The recommendations made by the IRC will be forwarded to the 
appropriate authorized Pfizer personnel for review and final decision. Pfizer will 
communicate such decisions, which may include summaries of aggregate analyses of safety 
data, to regulatory authorities and investigators, as appropriate. 
10.1.6. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT/CTIS, and/or 
www.pfizer.com, and other public registries and websites in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT/CTIS
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts CSR synopses and plain-language study results summaries on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the corresponding study results 
are posted to www.clinicaltrials.gov. CSR synopses will have personally identifiable 
information anonymized.
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Documents within marketing applications
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized.
Data sharing
Pfizer provides researchers secure access to participant-level data or full CSRs for the 
purposes of “bona-fide scientific research” that contributes to the scientific understanding of 
the disease, target, or compound class. Pfizer will make data from these trials available 
18 months after study completion. Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information anonymized.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.7. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
QTLs are predefined parameters that are monitored during the study. Important deviations 
from the QTLs and any remedial actions taken will be summarized in the CSR.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source records and documents.
This verification may also occur after study completion. It is important that the 
investigator(s) and their relevant personnel are available during the monitoring visits and 
possible audits or inspections and that sufficient time is devoted to the process.
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Monitoring details describing strategy, including definition of study-critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.8. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes a source document and its origin can be found in the Source 
Document Locator, which is maintained by the sponsor.
Description of the use of the computerized system is documented in the data management 
plan, which is maintained by the sponsor.
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The investigator must maintain accurate documentation (source record) that supports the 
information entered in the CRF.
The sponsor or designee will perform monitoring to confirm that data entered into the CRF 
by authorized site personnel are accurate, complete, and verifiable from source documents; 
that the safety and rights of participants are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.
10.1.9. Use of Medical Records
There may be instances when copies of medical records for certain cases are requested by 
Pfizer Safety, where ethically and scientifically justified and permitted by local regulations, 
to ensure participant safety.
Due to the potential for a participant to be re-identified from their medical records, the 
following actions must be taken when medical records are sent to the sponsor or sponsor 
designee:

The investigator or site staff must redact personal information from the medical record. 
The personal information includes, but is not limited to, the following: participant names 
or initials, participant dates (eg, birth date, date of hospital admission/discharge, date of 
death), participant identification numbers (eg, Social Security number, health insurance 
number, medical record number, hospital/institution identifier), participant location 
information (eg, street address, city, country, postal code, IP address), participant contact 
information (eg, telephone/fax number, email address).

Each medical record must be transmitted to the sponsor or sponsor designee using 
systems with technical and organizational security measures to ensure the protection of 
personal data (eg, Florence is the preferred system if available). 

There may be unplanned situations where the sponsor may request medical records 
(eg, sharing medical records so that the sponsor can provide study-related advice to the 
investigator). The medical records should be submitted according to the procedure 
described above. 
10.1.10. Study and Site Start and Closure
The study start date is the date of the first participant’s first visit.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor, including (but not limited to) 
regulatory authority decision, change in opinion of the IRB/EC, or change in benefit-risk 
assessment. Study sites will be closed upon study completion. A study site is considered 
closed when all required documents and study supplies have been collected and a study-site 
closure visit has been performed.
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The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/EC 
or local health authorities, the sponsor’s procedures, or the ICH GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.11. Publication Policy
For multicenter trials, the primary publication will be a joint publication developed by the 
investigator and Pfizer reporting the primary endpoint(s) of the study covering all study sites. 
The investigator agrees to refer to the primary publication in any subsequent publications. 
Pfizer will not provide any financial compensation for the investigator’s participation in the 
preparation of the primary congress abstract, poster, presentation, or primary manuscript for 
the study.
Investigators are free to publish individual center results that they deem to be clinically 
meaningful after publication of the overall results of the study or 12 months after primary 
completion date or study completion at all sites, whichever occurs first, subject to the other 
requirements described in this section.
The investigator will provide Pfizer an opportunity to review any proposed publication or 
any other type of disclosure of the study results (collectively, “publication”) before it is 
submitted or otherwise disclosed and will submit all publications to Pfizer 30 days before 
submission. 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 
upon request from Pfizer. This allows Pfizer to protect proprietary information and to provide 
comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study-intervention or Pfizer-related 
information necessary for the appropriate scientific presentation or understanding of the 
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study results. For joint publications, should there be disagreement regarding interpretation 
and/or presentation of specific analysis results, resolution of, and responsibility for, such 
disagreements will be the collective responsibility of all authors of the publication.
For all publications relating to the study, the investigator and Pfizer will comply with 
recognized ethical standards concerning publications and authorship, including those 
established by the International Committee of Medical Journal Editors. The investigator will 
disclose any relationship with Pfizer and any relevant potential conflicts of interest, including 
any financial or personal relationship with Pfizer, in any publications. All authors will have 
access to the relevant statistical tables, figures, and reports (in their original format) required 
to develop the publication.
10.1.12. Sponsor’s Medically Qualified Individual 
The contact information for the sponsor’s MQI for the study is documented in the study 
contact list located in the supporting study documentation/study portal or other electronic 
system.
To facilitate access to their investigator and the sponsor’s MQI for study-related medical 
questions or problems from nonstudy healthcare professionals, participants are provided with 
an ECC at the time of informed consent. The ECC contains, at a minimum, (a) protocol and 
study intervention identifiers, (b) participant’s study identification number, (c) site 
emergency phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center 
number.
The ECC is intended to augment, not replace, the established communication pathways 
between the participant and their investigator and site staff, and between the investigator and 
sponsor study team. The ECC is only to be used by healthcare professionals not involved in 
the research study, as a means of reaching the investigator or site staff related to the care of a 
participant. The Pfizer Call Center number is to be used when the investigator and site staff 
are unavailable. The Pfizer Call Center number is not for use by the participant directly; if a 
participant calls that number directly, they will be directed back to the investigator site.
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10.2. Appendix 2: Clinical Laboratory Tests
If appropriate, a pregnancy test will be performed at times defined in the SoA.

Pregnancy test (β-hCG): Local urine testing will be standard for the protocol unless 
serum testing is required by local regulation or IRB/EC for participants who are WOCBP.
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues. The investigator must review the laboratory report, 
document this review, and record any clinically relevant changes occurring during the study 
in the AE section of the CRF.
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. Any abnormal test results that meet 
any of the conditions below must be recorded as an AE:

Is associated with accompanying symptoms.

Requires additional diagnostic testing or medical/surgical intervention.

Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy.

Exacerbation of a chronic or intermittent preexisting condition, including an increase in 
either frequency and/or intensity of the condition.

New condition detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE or SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads 
to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2. Definition of an SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE.
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d. Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or nonpathogenic  
The event may be suspected from clinical symptoms or laboratory findings indicating 
an infection in a participant exposed to a Pfizer product. The terms “suspected 
transmission” and “transmission” are considered synonymous. These cases are 
considered unexpected and handled as serious expedited cases by pharmacovigilance 
personnel. Such cases are also considered for reporting as product defects, if 
appropriate.
g. Other situations:

Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
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10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period 
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs using the Vaccine SAE Report Form or via PSSA to Pfizer Safety
throughout the active collection period. These requirements are delineated for 3 types of 
events: (1) SAEs; (2) nonserious AEs; and (3) exposure to the study intervention under 
study during pregnancy or breastfeeding, and occupational exposure. 
It should be noted that the Vaccine SAE Report Form/PSSA for reporting of SAE 
information is not the same as the AE page of the CRF. When the same data are collected, 
the forms must be completed in a consistent manner. AEs should be recorded using 
concise medical terminology and the same AE term should be used on both the CRF and 
the Vaccine SAE Report Form/PSSA for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine 
SAE Report Form/PSSA
to Pfizer Safety Within 
24 Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding 
All AEs or SAEs associated 
with EDP or EDB
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)*
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE)**
Environmental or 
occupational exposure to 
the product under study to 
a nonparticipant (not 
involving EDP or EDB)
None. Exposure to a study 
nonparticipant is not 
collected on the CRF
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported***
*
EDP (with or without an associated SAE) is reported to Pfizer Safety using the Vaccine SAE Report 
Form and EDP Supplemental Form or via PSSA. 
**
EDB is reported to Pfizer Safety using the Vaccine SAE Report Form or via PSSA, which would 
also include details of any SAE that might be associated with the EDB. 
*** Environmental or occupational exposure: AEs or SAEs associated with occupational exposure 
are reported to Pfizer Safety using the Vaccine SAE Report Form or via PSSA. 
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
When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event.

The investigator will then record all relevant AE or SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the Vaccine SAE Report Form/AE or 
SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety. Refer to Section 10.1.9 for actions that must be taken 
when medical records are sent to the sponsor or sponsor designee.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE or SAE.
Assessment of Intensity
GRADE 
If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING to 
describe the maximum intensity of the AE. For purposes of consistency, 
these intensity grades are defined as follows:
1
MILD
Does not interfere with participant’s usual 
function.
2
MODERATE
Interferes to some extent with participant’s usual 
function.
3
SEVERE
Interferes significantly with participant’s usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent 
intervention indicated.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE or SAE. The investigator will use clinical judgment to 
determine the relationship.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in their assessment.

For each AE or SAE, the investigator must document in the medical notes that they 
have reviewed the AE or SAE and have provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the sponsor.

The investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor. In addition, if the investigator determines that an 
SAE is associated with study procedures, the investigator must record this causal 
relationship in the source documents and CRF, and report such an assessment in the 
dedicated section of the Vaccine SAE Report Form/PSSA and in accordance with the 
SAE reporting requirements.
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Follow-Up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the 
sponsor, to elucidate the nature and/or causality of the AE or SAE as fully as possible.
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Pfizer Safety with a copy of any postmortem 
findings, including histopathology. 

New or updated information will be recorded in the originally submitted documents.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic DCT

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
DCT (eg, eSAE or PSSA).

If the electronic system is unavailable, then the site will use the paper SAE report form 
(see next section) to report the event within 24 hours.

The site will enter the SAE data into the electronic DCT (eg, eSAE or PSSA) or paper 
form (as applicable) as soon as the data become available.

After the study is completed at a given site, the electronic DCT will be taken off-line to 
prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic DCT has been taken off-line, 
then the site can report this information on a paper SAE form (see next section) or to 
Pfizer Safety by telephone.
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SAE Reporting to Pfizer Safety via the Vaccine SAE Report Form

Facsimile transmission of the Vaccine SAE Report Form is one of the preferred 
methods to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, an alternative method should be 
used, eg, secured (Transport Layer Security) or password-protected email. If none of 
these methods can be used, notification by telephone is acceptable with a copy of the 
Vaccine SAE Report Form sent by overnight mail or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Report Form pages within the designated reporting 
time frames.
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10.4. Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent 
on a long-term and persistent basis) and agree to remain abstinent.
OR

Must agree to use contraception/barrier as detailed below:

Agree to use a male condom, and should also be advised of the benefit for a female 
partner to use a highly effective method of contraception as a condom may break or 
leak, when having sexual intercourse with a WOCBP who is not currently pregnant.
OR

Be vasectomized, with the absence of sperm having been confirmed.
10.4.2. Female Participant Reproductive Inclusion Criteria
The criteria below are part of inclusion criterion 1 (Age and Sex; Section 5.1) and specify the 
reproductive requirements for including female participants. Refer to Section 10.4.4 for a 
complete list of contraceptive methods permitted in the study. 
A female participant is eligible to participate if she is not pregnant or breastfeeding and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and agrees to use an acceptable contraceptive method during the 
intervention period (for a minimum of 28 days after the last dose of study intervention). 
The investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention.
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The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea or oligomenorrhea) and a menstrual cycle cannot be 
confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to a medical cause other than the above
(eg, mullerian agenesis, androgen insensitivity), investigator discretion should be applied to 
determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. In addition:

A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 

A female on HRT and whose menopausal status is in doubt will be required to use 
one of the highly effective nonestrogen hormonal contraception methods if she
wishes to continue her HRT during the study. Otherwise, she must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment.
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10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
The following contraceptive methods are appropriate for this study:
Highly Effective Methods That Have Low User Dependency 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner:

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be 
used. The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal.
7. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
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8. Sexual abstinence

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.
Other Effective Methods
9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.
10. Male or female condom, with or without spermicide.
11. Cervical cap, diaphragm, or sponge with spermicide.
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).
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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
“susceptible” to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
LFTs are not required as a routine safety monitoring procedure in this study. However, should 
an investigator deem it necessary to assess LFTs because a participant presents with clinical 
signs/symptoms, such LFT results should be managed and followed as described below.
In the majority of DILI cases, elevations in AST and/or ALT precede T bili elevations 
(>2 × ULN) by several days or weeks. The increase in T bili typically occurs while AST/ALT 
is/are still elevated above 3 × ULN (ie, AST/ALT and T bili values will be elevated within 
the same laboratory sample). In rare instances, by the time T bili 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 T bili that meet the 
criteria outlined below are considered potential DILI (assessed per Hy’s law criteria) cases
and should always be considered important medical events, even before all other possible 
causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and T bili baseline values within the normal range who 
subsequently present with AST OR ALT values ≥3 × ULN AND a T bili value ≥2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value 2 × ULN or not 
available.

For participants with baseline AST OR ALT OR T bili 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 T bili above the normal range: T bili level increased from
baseline value by an amount of ≥1 × ULN or if the value reaches ≥3 × ULN 
(whichever is smaller).
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Rises in AST/ALT and T bili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and T bili for suspected Hy’s law
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, eosinophils (%), and alkaline phosphatase. Consideration should also be 
given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology. A detailed history, including relevant information, 
such as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, total bile acids, liver imaging (eg, biliary tract), and 
collection of serum samples for acetaminophen/paracetamol drug and/or protein adduct 
levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
T bili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.6. Appendix 6: Kidney Safety Monitoring Guidelines
10.6.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury
Standard kidney safety monitoring requires assessment of baseline and postbaseline Screat 
measurement to estimate kidney function [Screat-based eGFR] or creatinine clearance 
[eCrCl]). Baseline and postbaseline Scys makes it feasible to distinguish AKI from other 
causes of Screat increase. If Screat increase is confirmed after baseline, then reflex 
measurement of Scys is indicated. 
ADULTS: Currently, 2021 CKD-EPI eGFR equations (Screat-only based and combined 
Screat plus Scys-based) are valid for use in adults only. At baseline Screat and Scys values 
are needed to calculate 2021 CKD-EPI eGFR by Screat-only based equation (see the table in 
Section 10.6.2.1) and by combined Screat plus Scys-based equation. When postbaseline 
Screat increase ≥0.3 mg/dL is confirmed, then reflex Scys measurement is needed to enable 
postbaseline comparison of eGFR changes (Screat-only based eGFR and combined Screat 
plus Scys eGFR). 
Regardless of whether kidney function monitoring tests are required as a routine safety 
monitoring procedure in the study, if the investigator or sponsor deems it necessary to further 
assess kidney safety and quantify kidney function, then these test results should be managed 
and followed per standard of care.
10.6.2. Age-Specific Kidney Function Calculation Recommendations
10.6.2.1. Adults (18 Years and Above)—2021 CKD-EPI Equations
eGFR (mL/min/1.73m²)
2021 
CKD-EPI 
Screat Only
Screat
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤.7
N/A
eGFR = 143 × (Screat/0.7)-0.241 × (0.9938)Age
Female
if 0.7
N/A
eGFR = 143 × (Screat/0.7)-1.200 × (0.9938)Age
Male
if ≤0.9
N/A
eGFR = 142 × (Screat/0.9)-0.302 × (0.9938)Age
Male
if 0.9
N/A
eGFR = 142 × (Screat/0.9)-1.200 × (0.9938)Age
2021 
CKD-EPI 
Screat-Scys 
Combined
Screat
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤0.7
if ≤0.8
eGFR = 130 × (Screat/0.7)-0.219 × (Scys/0.8)-0.323 × (0.9961)Age
Female
if ≤0.7
if 0.8
eGFR = 130 × (Screat/0.7)-0.219 × (Scys/0.8)-0.778 × (0.9961)Age
Female
if 0.7
if ≤0.8
eGFR = 130 × (Screat/0.7)-0.544 × (Scys/0.8)-0.323 × (0.9961)Age
Female
if 0.7
if 0.8
eGFR = 130 × (Screat/0.7)-0.544 × (Scys/0.8)-0.778 × (0.9961)Age
Male
if ≤0.9
if ≤0.8
eGFR = 135 × (Screat/0.9)-0.144 × (Scys/0.8)-0.323 × (0.9961)Age
Male
if ≤0.9
if 0.8
eGFR = 135 × (Screat/0.9)-0.144 × (Scys/0.8)-0.778 × (0.9961)Age
Male
if 0.9
if ≤0.8
eGFR = 135 × (Screat/0.9)-0.544 × (Scys/0.8)-0.323 × (0.9961)Age
Male
if 0.9
if 0.8
eGFR = 135 × (Screat/0.9)-0.544 × (Scys/0.8)-0.778 × (0.9961)Age
Inker LA et al. N Engl J Med. 2021;385(19):1737-49.41
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10.6.3. Kidney Function Calculation Tools
The sponsor has provided the following resources to investigational sites when required to 
calculate age-specific kidney function at the screening, baseline, and postbaseline visits. Site 
calculations of kidney function can be performed manually, using the age-appropriate 
formulae (see Section 10.6.2) and can use recommended online kidney function calculators 
to reduce the likelihood of a calculation error. 
The United States National Kidney Foundation Online Calculators. 

Adults (18 years and above) - 2021 CKD-EPI Creatinine Online Calculator (eGFR): 
https://www.kidney.org/professionals/KDOQI/gfr_calculator

Adolescents (12 years to 18 years) - Cockcroft-Gault Formula (eCrCl): 
https://www.kidney.org/professionals/kdoqi/gfr_calculatorCoc

Investigational sites are responsible to ensure that the accurate age-specific equation is 
selected and that the correct units are used for serum creatinine (mg/dL only), serum 
cystatin C (mg/L only), total body weight (kg only), and age (years). Investigators are 
expected to (i) review and confirm correctness of the kidney function calculation results 
and (ii) evaluate the calculated value within the context of historical information 
available to them in the participant’s medical record. Investigators are responsible for the 
clinical oversight of the participant eligibility process, kidney function calculation, and 
dose selection and adjustments per study protocol. Investigators are encouraged to direct 
questions or uncertainties regarding kidney function and dosing to the Pfizer Clinical 
Team and Medical Monitor, if needed.
10.6.4. Adverse Event Grading for Kidney Safety Laboratory Abnormalities
AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to KDIGO
criteria for both pediatric and adult participants.
KDIGO criteria 
grade (G)
Study 
Population
G1
G2
G3
G4
G5
Decreased 
Kidney Function 
due to either 
Acute or Chronic 
Kidney Injury 
Adult 
participants
eGFR 
(mL/min/1.73m²)
≥90 
≥60 to 89
30 to 59 
15 to 29
15
KDIGO albuminuria (A) 
criteria
A1
A2
A3
Albumin-to-creatinine ratio 
(ACR)
30 mg/g
OR     
3 mg/mmol 
30 to 300 mg/g
OR 
3 to 30 mg/mmol
300 mg/g 
OR 
30 mg/mmol
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10.7. Appendix 7: AEs, ADEs, SAEs, SADEs, USADEs, and Device Deficiencies:
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting in 
Medical Device Studies
Definitions of a Medical Device Deficiency
The definitions and procedures detailed in this appendix are in accordance with ISO 14155
and the European MDR 2017/745 for clinical device research (if applicable). 
Both the investigator and the sponsor will comply with all local reporting requirements for 
medical devices.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.7.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined in Appendix 3 (Section 10.3.1).

An ADE is defined as an AE related to the use of an investigational medical device. 
This definition includes any AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device as well as any event resulting from use error or from 
intentional misuse of the investigational medical device.
10.7.2. Definition of SAE, SADE, and USADE
SAE Definition

An SAE is defined in Appendix 3 (Section 10.3.2).
SADE Definition

An SADE is defined as an ADE that has resulted in any of the consequences 
characteristic of an SAE.

Any device deficiency that might have led to an SAE if appropriate action had not been 
taken, intervention had not occurred, or circumstances had been less fortunate.
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USADE Definition

A USADE (also identified as UADE in US Regulation 21 CFR 813.3) is an SADE that
by its nature, incidence, severity, or outcome has not been identified in the current 
version of the risk analysis management file.
10.7.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance. Device deficiencies include 
malfunctions, use errors, and inadequate information supplied by the manufacturer.
10.7.4. Recording/Reporting and Follow-Up of Medical Device Deficiencies
Device Deficiency Recording

When a device deficiency occurs, it is the responsibility of the investigator to review 
all documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant device deficiency information in the 
participant’s medical records, in accordance with the investigator’s normal clinical 
practice.  

If an AE (either serious or nonserious) associated with the device deficiency occurs, 
then the AE must be entered into the AE section of the CRF.

The investigator will notify the sponsor study team by contact method, eg, telephone, 
email within 1 business day of determining that the incident meets the protocol 
definition of a medical device deficiency.

The sponsor study team will capture the required information on the Medical Device 
Complaint form along with any associated AE (either serious or nonserious) when 
applicable and send to the appropriate product quality complaint group.

If the investigator determines that the medical device deficiency may have injured the 
participant (ie, the medical device deficiency is associated with an AE or SAE), then 
the investigator will attempt to establish a diagnosis of the event based on signs,
symptoms, and/or other clinical information. Whenever possible, the diagnosis will be 
documented in the participant’s medical record and recorded as the AE or SAE rather 
than the individual signs/symptoms. All relevant details related to the role of the device 
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in regard to the SAE must be included in the Vaccine SAE Report Form as outlined in 
Sections 8.4.1.1 and 8.4.1.2. 

There may be instances when copies of medical records for certain cases are requested 
by Pfizer Safety. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Pfizer Safety. Refer to Section 10.1.9 for actions that must be taken 
when medical records are sent to the sponsor or sponsor designee.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.

A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency. This includes any amendment to the device design to prevent recurrence.
Assessment of Causality Occurring in Conjunction With a Medical Device Deficiency

If an AE or SAE has occurred in conjunction with a medical device deficiency, the 
investigator must assess the relationship between each occurrence of the AE or SAE 
and the medical device deficiency. The investigator will use clinical judgment to 
determine the relationship.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in their assessment.

For each device deficiency, the investigator must document in the medical notes that 
they have reviewed the device deficiency and have provided an assessment of 
causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the sponsor.
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
The investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-Up of Medical Device Deficiency

Follow-up applies to all participants, including those who discontinue study 
intervention.

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the device deficiency as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

New or updated information regarding the nature of the device deficiency will be 
recorded in the originally completed Medical Device Complaint form by the sponsor 
study team.

New or updated information regarding any SAE that was potentially associated with 
the medical device deficiency will be submitted to Pfizer Safety on the Vaccine SAE 
Report Form within 24 hours of receipt of the information, according to the 
requirements provided in Appendix 3.
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10.8. Appendix 8: Abbreviations
The following is a list of abbreviations that may be used in the protocol. 
Abbreviation
Term
A1 to A3
albuminuria (KDIGO albuminuria severity standardization)
ACIP
Advisory Committee on Immunization Practices
ACR
albumin-to-creatinine ratio
ADE
adverse device effect
AE
adverse event
AESI
adverse event of special interest
AKI
acute kidney injury
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AxMP
auxiliary medicinal product
BEVS
baculovirus expression vector system
-hCG
-human chorionic gonadotropin
BMI
body mass index
BNT162b2
Pfizer-BioNTech COVID-19 vaccine
BSA
body surface area
CBER
Center for Biologics Evaluation and Research (United States)
CDC
Centers for Disease Control and Prevention (United States)
CFR
Code of Federal Regulations (United States)
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
CTIS
Clinical Trial Information System
DCT
data collection tool
DILI
drug-induced liver injury
DNA
deoxyribonucleic acid
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram or electrocardiography
eCrCl
estimated creatinine clearance
eCRF
electronic case report form
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Abbreviation
Term
EDB
exposure during breastfeeding
e-diary
electronic diary
EDP
exposure during pregnancy
eGFR
estimated glomerular filtration rate
eICD
electronic informed consent document
EMA
European Medicines Agency
eSAE
electronic serious adverse event
EU
European Union
EUA
emergency use authorization
EudraCT
European Union Drug Regulating Authorities Clinical Trials 
(European Clinical Trials Database)
FDA
Food and Drug Administration (United States)
FSH
follicle-stimulating hormone
G1 to G5
Grade (KDIGO eGFR category standardization)
GBS
Guillain-Barré syndrome
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HA
hemagglutinin
HAI
hemagglutinin inhibition assay
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
Ht
height
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
ID
identification
IgG
immunoglobulin G
IMP
investigational medicinal product
IND
investigational new drug
INR
international normalized ratio
IP
Internet Protocol
IPAL
investigational product accountability log
IPM
investigational product manual
IRB
institutional review board
IRC
internal review committee
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Abbreviation
Term
IRT
interactive response technology
ISO
International Organization for Standardization
IV
intravenous(ly)
IWR
interactive Web-based response
K
Proportionality constant for Schwartz equations (kidney function)
KDIGO
Kidney Disease: Improving Global Outcomes
LFT
liver function test
MDR
medical device regulation
modRNA
nucleoside-modified messenger ribonucleic acid
MQI
medically qualified individual
mRNA
messenger ribonucleic acid
NA
neuraminidase
N/A
not applicable
NAAT
nucleic acid amplification test
NIMP
noninvestigational medicinal product
Omi
Omicron
PFS
prefilled syringe
PI
principal investigator
PSSA
Pfizer's Serious Adverse Event Submission Assistant
PT
prothrombin time
QTL
quality tolerance limit
RCDC
reverse cumulative distribution curve
RIV
recombinant influenza virus (Flublok Quadrivalent)
RNA
ribonucleic acid
S1
spike protein S1 subunit
SADE
serious adverse device effect
SAE
serious adverse event
SAP
statistical analysis plan
SARS
severe acute respiratory syndrome
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
Screat
serum creatinine
Scys
serum cystatin C
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
T bili
total bilirubin
Th1
T-helper type 1
UADE
unanticipated adverse device effect
ULN
upper limit of normal
US
United States
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Abbreviation
Term
USADE
unanticipated serious adverse device effect
VE
vaccine efficacy
WHO
World Health Organization
WOCBP
woman/women of childbearing potential
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