AN INTERVENTIONAL, RANDOMIZED, ACTIVE-CONTROLLED, PHASE 1/2/3 STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF BNT162b RNA-BASED VACCINE CANDIDATES IN COVID-19 VACCINE-EXPERIENCED HEALTHY INDIVIDUALS
Phase: PHASE2
Conditions: SARS-CoV-2 Infection, COVID-19
Sponsor: BioNTech SE

PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 1
AN INTERVENTIONAL, RANDOMIZED, ACTIVE-CONTROLLED, PHASE 1/2/3
STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND 
IMMUNOGENICITY OF BNT162b RNA-BASED VACCINE CANDIDATES IN 
COVID-19 VACCINE–EXPERIENCED HEALTHY INDIVIDUALS 
Study Sponsor:
BioNTech
Study Conducted by:
Pfizer
Study Intervention Number:
PF-07302048
Study Intervention Name:
BNT162b RNA-Based COVID-19 Vaccine
US IND Numbers:
19736 and 29784
EudraCT/CTIS Number:
2022-002008-19
ClinicalTrials.gov ID:
NCT05472038
Pediatric Investigational Plan Number:
EMEA-002861-PIP02-20-M03
Protocol Number:
C4591044
Phase:
1/2/3
Brief Title:
A Study to Learn About New COVID-19 RNA Vaccine Candidates in COVID-19 
Vaccine–Experienced Healthy Individuals 
This document and accompanying materials contain confidential information belonging to Pfizer. Except 
as otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) 
or use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 2
Document History
Document 
Version Date
Original protocol
14 June 2022
Amendment 1
27 July 2022
Amendment 2
24 August 2022
Amendment 3
14 April 2023 (protocol amendment 3 was not 
implemented)
Amendment 4
26 May 2023
Amendment 5
23 June 2023 (protocol amendment 5 was not 
implemented)
Amendment 6
27 July 2023
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any protocol administrative 
clarification letter. 
Amendment 6 (27 July 2023)
Overall Rationale for the Amendment: 
Addition of BNT162b6 vaccine into Cohort 4 to describe the immune response to this new 
30-µg bivalent Omicron BA.4/BA.5–modified BNT162b vaccine:  

BNT162b6 Bivalent (Original/OMI BA.4/BA.5) 
given to mRNA COVID-19 vaccine–experienced participants 18 through 55 years of age.  
Updated corresponding objectives and details in the statistical methods sections.  Study 
intervention details and background information supporting the inclusion of this vaccine 
were also added.
Protocol Amendment Summary of Changes Table 
Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Cover page
Added IND number 29784
and removed IND number 
29525.
Amended the title to 
remove “bivalent” and 
“booster.”
Per feedback from 
FDA/CBER, studies of 
BNT162b6 and 
BNT162b7 are to be 
conducted together 
under a new IND.
Since Cohort 4 vaccine 
candidates include a
monovalent vaccine. 
Substantial
090177e19e249a01\Approved\Approved On: 27-Jul-2023 15:57 (GMT)

PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
To align with recent 
simplified public health 
vaccination schedules.
Protocol Summary: 
Section 1.1, Section 1.2,
and Section 1.3 
Updated the text, tables, 
and schema with respect to 
the changes within
Cohort 4. 
To obtain data on the 
new 30-µg bivalent
Omicron BA.4/BA.5–
modified BNT162b6
vaccine in participants 
18 through 55 years of 
age.
Substantial
Section 2
Introduction
Added text to provide 
background and rationale 
for the addition of the 
BNT162b6 vaccine into 
Cohort 4.
To obtain data on the 
new 30-µg bivalent 
BNT162b6 vaccine.
Substantial
Section 2.3.1
Risk Assessment
Updated with new 
information regarding 
myocarditis and 
pericarditis rates in ages 12 
through 17 years and after 
additional doses. Applied 
corrections to align with 
the SRSD.
To align with SRSD.
Substantial
Section 1.1 Synopsis and
Section 3
Objectives, Endpoints, 
and Estimands
Updated the text with 
respect to the addition of 
the BNT162b6 vaccine 
into Cohort 4.
To describe the analysis 
of data from Cohort 4.
Substantial
Section 4
Study Design
Updated Cohort 4–specific 
information in Section 4.1.
To update for the 
addition of the 
BNT162b6 vaccine into 
Cohort 4.
Substantial
Section 6.1
Study Interventions 
Administered
Updated the Cohort 4
vaccines and study 
intervention details.
To update for the 
addition of the 
BNT162b6 vaccine into 
Cohort 4.
Substantial
Section 6.3
Assignment to Study 
Intervention
Updated the Cohort 4
randomization scheme.
To update for the 
addition of the 
BNT162b6 vaccine into 
Cohort 4.
Substantial
Section 9
Statistical 
Considerations
Updated the analysis of 
data from Cohort 4.
To update for the 
addition of the 
BNT162b6 vaccine into 
Cohort 4.
Substantial
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 5.2
Exclusion Criteria
Added exclusion 
criterion 10 to exclude any 
history of 
myocarditis/pericarditis 
from Cohort 4 onwards.
Per feedback from 
FDA/CBER.
Substantial
Section 1.3 
Schedule of Activities,
Section 8.4.8
Adverse Events of 
Special Interest, and
Section 8.10.11
Additional Procedures 
for Monitoring of 
Potential Pericarditis or
Myocarditis
Updated to: 
- extend monitoring of 
cardiac symptoms through 
6 weeks after study 
intervention
administration.
- amend wording for 
cardiologist evaluation.
- classify the diagnosis of 
myocarditis of pericarditis 
as an important medical 
event requiring reporting 
as an SAE.
Per feedback from 
FDA/CBER.
Substantial
Section 5.2
Exclusion Criteria and
Section 6.9.1
Prohibited During the 
Study
Updated to clarify 
exclusion of monoclonal 
antibodies.
To clarify and align with 
other C459 protocols 
based on site feedback.
Nonsubstantial
Section 8.3.4
Electronic Diary
Added text related to 
e-diary reminder 
notifications and capture
of missed diary data in 
CRF.
To include in the 
protocol per FDA/CBER 
feedback. 
Nonsubstantial
Section 8.10.1
Visit 1 - Study 
Intervention 
Administration - Day 1
Updated text related to 
IRT notifications.
To clarify which IRT
notifications are received 
by blinded versus 
unblinded team 
members.
Nonsubstantial
Section 9.1.1
Estimands
Updated to remove 
“e-diary” when referencing 
reactogenicity data.
To align with data 
handling where 
reactogenicity data are
compiled from the 
e-diary and CRF.
Nonsubstantial
Section 10.8
Appendix 8: Protocol
Amendment History
Added Amendment 4
summary of changes.
Clarified Amendment 3 
and Amendment 5.
Protocol template 
requirement.
Nonsubstantial
Section 10.9
Appendix 9: 
Abbreviations
Updated with the 
BNT162b6 vaccine.
Administrative updates 
for the addition of the
BNT162b6 vaccine to 
the protocol.
Nonsubstantial
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 11
References
Additional references for 
epidemiological data and 
new variant mutations.
To support statements 
made throughout the 
synopsis and 
introduction.
Nonsubstantial
All
Added reference to PSSA 
for reporting of safety 
information to Pfizer 
Safety and edited text in 
line with current process.
To capture reporting 
process to Pfizer Safety 
via PSSA.
Nonsubstantial
All
Removal of reference to 
“booster” in Cohort 4 and 
in relation to current public 
health vaccination 
schedule text.
To align with recent 
simplified public health 
vaccination schedules.
Nonsubstantial
090177e19e249a01\Approved\Approved On: 27-Jul-2023 15:57 (GMT)

PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 6
TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................11
1. PROTOCOL SUMMARY...................................................................................................12
1.1. Synopsis ..................................................................................................................12
1.2. Schema ....................................................................................................................32
1.3. Schedule of Activities .............................................................................................33
2. INTRODUCTION ...............................................................................................................41
2.1. Study Rationale .......................................................................................................41
2.2. Background .............................................................................................................43
2.2.1. Clinical Overview.......................................................................................44
2.3. Benefit/Risk Assessment.........................................................................................47
2.3.1. Risk Assessment.........................................................................................48
2.3.2. Benefit Assessment.....................................................................................50
2.3.3. Overall Benefit/Risk Conclusion................................................................50
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ...........................................................50
4. STUDY DESIGN.................................................................................................................56
4.1. Overall Design.........................................................................................................56
4.2. Scientific Rationale for Study Design.....................................................................59
4.2.1. Diversity of Study Population ....................................................................60
4.2.2. Choice of Contraception/Barrier Requirements .........................................60
4.3. Justification for Dose ..............................................................................................60
4.4. End of Study Definition ..........................................................................................61
5. STUDY POPULATION......................................................................................................61
5.1. Inclusion Criteria.....................................................................................................61
5.2. Exclusion Criteria....................................................................................................63
5.3. Lifestyle Considerations..........................................................................................64
5.3.1. Contraception..............................................................................................64
5.4. Screen Failures ........................................................................................................65
5.5. Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention...........................65
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................66
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6.1. Study Interventions Administered...........................................................................66
6.1.1. Administration............................................................................................73
6.2. Preparation, Handling, Storage, and Accountability...............................................73
6.2.1. Preparation and Dispensing........................................................................74
6.3. Assignment to Study Intervention...........................................................................74
6.4. Blinding...................................................................................................................75
6.4.1. Blinding of Participants..............................................................................75
6.4.2. Blinding of Site Personnel..........................................................................76
6.4.3. Blinding of the Sponsor..............................................................................76
6.4.4. Breaking the Blind......................................................................................77
6.5. Study Intervention Compliance...............................................................................77
6.6. Dose Modification...................................................................................................77
6.7. Continued Access to Study Intervention After the End of the Study......................77
6.8. Treatment of Overdose............................................................................................78
6.9. Prior and Concomitant Therapy..............................................................................78
6.9.1. Prohibited During the Study.......................................................................78
6.9.2. Permitted During the Study ........................................................................79
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................80
7.1. Discontinuation of Study Intervention ....................................................................80
7.2. Participant Discontinuation/Withdrawal From the Study.......................................80
7.2.1. Withdrawal of Consent...............................................................................80
7.3. Lost to Follow-Up ...................................................................................................81
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................81
8.1. Administrative and Baseline Procedures.................................................................81
8.1.1. Baseline Procedures....................................................................................82
8.2. Efficacy and/or Immunogenicity Assessments .......................................................83
8.2.1. Surveillance for COVID-19........................................................................83
8.2.2. Vaccine-Induced Immunogenicity..............................................................85
8.2.3. N-Binding Antibody Test ...........................................................................86
8.2.4. Biological Samples.....................................................................................86
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8.3. Safety Assessments .................................................................................................86
8.3.1. Physical Examinations................................................................................87
8.3.2. Vital Signs ..................................................................................................87
8.3.3. Clinical Safety Laboratory Assessments ....................................................87
8.3.4. Electronic Diary..........................................................................................87
8.3.4.1. Grading Scales...........................................................................88
8.3.4.2. Local Reactions.........................................................................88
8.3.4.3. Systemic Events ........................................................................89
8.3.4.4. Fever..........................................................................................91
8.3.4.5. Antipyretic/Analgesic Medication ............................................91
8.3.5. Pregnancy Testing ......................................................................................91
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................92
8.4.1. Time Period and Frequency for Collecting AE and SAE Information.......92
8.4.1.1. Reporting SAEs to Pfizer Safety...............................................93
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF...................93
8.4.2. Method of Detecting AEs and SAEs ..........................................................93
8.4.3. Follow-Up of AEs and SAEs......................................................................94
8.4.4. Regulatory Reporting Requirements for SAEs...........................................94
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................94
8.4.5.1. Exposure During Pregnancy......................................................95
8.4.5.2. Exposure During Breastfeeding ................................................96
8.4.5.3. Occupational Exposure .............................................................97
8.4.6. Cardiovascular and Death Events...............................................................97
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................97
8.4.8. Adverse Events of Special Interest.............................................................98
8.4.8.1. Lack of Efficacy........................................................................99
8.4.9. Medical Device Deficiencies......................................................................99
8.4.10. Vaccination Errors....................................................................................99
8.5. Pharmacokinetics ..................................................................................................100
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8.6. Genetics.................................................................................................................100
8.7. Biomarkers ............................................................................................................100
8.8. Immunogenicity Assessments...............................................................................100
8.9. Health Economics .................................................................................................100
8.10. Study Procedures.................................................................................................100
8.10.1. Visit 1 – Study Intervention Administration – Day 1.............................100
8.10.2. Visit 2 – 1-Week Follow-Up Visit (6 to 8 Days After Visit 1) ..............104
8.10.3. Visit 3 – 1-Month Follow-Up Visit (28 to 35 Days After Visit 1).........105
8.10.4. Visit 4 – 3-Month Follow-Up Visit (84 to 98 Days After Visit 1).........106
8.10.5. Visit 5 – 6-Month Follow-Up Visit (175 to 189 Days After Visit 1).....107
8.10.6. Unscheduled Visit for a Grade 3 or Suspected Grade 4 Reaction..........108
8.10.7. COVID-19 and MIS-C Surveillance ......................................................109
8.10.8. Potential COVID-19 Illness Visit (Optimally Within 3 Days After 
Potential COVID-19 Illness Onset) ...............................................................110
8.10.9. Potential COVID-19 Convalescent Visit (28 to 35 Days After 
Potential  COVID-19 Illness Visit)................................................................112
8.10.10. SARS-CoV-2 NAAT Results ...............................................................112
8.10.11. Additional Procedures for Monitoring of Potential Myocarditis or 
Pericarditis .....................................................................................................113
8.10.12. Communication and Use of Technology..............................................114
9. STATISTICAL CONSIDERATIONS ..............................................................................114
9.1. Statistical Hypothesis ............................................................................................114
9.1.1. Estimands..................................................................................................118
9.1.2. Multiplicity Adjustment............................................................................118
9.2. Analysis Sets .........................................................................................................119
9.3. Statistical Analyses ...............................................................................................119
9.3.1. General Considerations.............................................................................119
9.3.1.1. Analyses for Binary Data ........................................................120
9.3.1.2. Analyses for Continuous Data.................................................120
9.3.1.3. Geometric Means ....................................................................120
9.3.1.4. Geometric Mean Fold Rises....................................................120
9.3.1.5. Reverse Cumulative Distribution Curves................................121
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9.3.2. Primary Endpoints/Estimands Analysis ...................................................121
9.3.3. Secondary Endpoints ................................................................................124
9.3.4. Exploratory Endpoints..............................................................................125
9.4. Interim Analyses ...................................................................................................127
9.4.1. Analysis Timing........................................................................................127
9.5. Sample Size Determination...................................................................................127
10. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS........................................................................................................130
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............130
10.1.1. Regulatory and Ethical Considerations ..................................................130
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................130
10.1.2. Financial Disclosure ...............................................................................131
10.1.3. Informed Consent/Assent Process ..........................................................131
10.1.4. Data Protection .......................................................................................132
10.1.5. Committees Structure .............................................................................133
10.1.5.1. Data Monitoring Committee .................................................133
10.1.6. Dissemination of Clinical Study Data ....................................................133
10.1.7. Data Quality Assurance ..........................................................................134
10.1.8. Source Documents..................................................................................136
10.1.9. Study and Site Start and Closure ............................................................136
10.1.10. Publication Policy.................................................................................137
10.1.11. Sponsor’s Medically Qualified Individual............................................138
10.2. Appendix 2: Clinical Laboratory Tests ...............................................................138
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ...................................................................139
10.3.1. Definition of AE .....................................................................................139
10.3.2. Definition of an SAE ..............................................................................140
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period..........................................................................142
10.3.4. Reporting of SAEs..................................................................................145
10.4. Appendix 4: Contraceptive and Barrier Guidance ..............................................147
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10.4.1. Male Participant Reproductive Inclusion Criteria..................................147
10.4.2. Female Participant Reproductive Inclusion Criteria...............................147
10.4.3. Woman of Childbearing Potential ..........................................................148
10.4.4. Contraception Methods...........................................................................149
10.5. Appendix 5: Genetics..........................................................................................150
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments .....151
10.7. Appendix 7: Kidney Safety Monitoring Guidelines ...........................................153
10.7.1. Laboratory Assessment of Change in Kidney Function and 
Detection of Kidney Injury............................................................................153
10.7.2. Age-Specific Kidney Function Calculation Recommendations.............153
10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI 
Equations .........................................................................................153
10.7.3. Adverse Event Grading for Kidney Safety Laboratory 
Abnormalities.................................................................................................153
10.8. Appendix 8: Protocol Amendment History.........................................................154
10.9. Appendix 9: Abbreviations .................................................................................165
11. REFERENCES ................................................................................................................170
LIST OF TABLES
Table 1.
Cohort 2 Design........................................................................................57
Table 2.
Cohort 2 Immunogenicity Control Groups From C4591031 
Substudy E................................................................................................58
Table 3.
Cohort 3 Design........................................................................................58
Table 4.
Cohort 4 Design........................................................................................59
Table 5.
Local Reaction Grading Scale ..................................................................89
Table 6.
Systemic Event Grading Scale..................................................................90
Table 7.
Scale for Fever..........................................................................................91
Table 8.
Probability of Observing at Least 1 AE by Assumed True Event 
Rate.........................................................................................................127
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1. PROTOCOL SUMMARY
1.1. Synopsis
Protocol Title:
An Interventional, Randomized, Active-Controlled, Phase 1/2/3 Study to Investigate the 
Safety, Tolerability, and Immunogenicity of BNT162b RNA-Based Vaccine Candidates in 
COVID-19 Vaccine–Experienced Healthy Individuals
Brief Title:
A Study to Learn About New COVID-19 RNA Vaccine Candidates in COVID-19 Vaccine–
Experienced Healthy Individuals
Regulatory Agency Identification Numbers:
US IND Number:
19736 and 29784
EudraCT/CTIS Number:
2022-002008-19
ClinicalTrials.gov ID:
NCT05472038
Pediatric Investigational Plan Number:
EMEA-002861-PIP02-20-M03
Protocol Number:
C4591044
Phase:
1/2/3
Rationale:
BNT162b2 (Comirnaty®) is an RNA-based vaccine that, as of April 2022, was granted full 
marketing authorization, conditional marketing authorization, EUA, or temporary 
authorization in a total of more than 140 countries for the prevention of COVID-19 caused 
by SARS-CoV-2. The vaccine encodes the spike protein with a modRNA, is encapsulated in 
RNA-LNPs, and has demonstrated potent immunogenicity, high VE, and a favorable safety 
profile in Phase 1, 2, and 3 human trials, as well as in real-world usage. Since the start of the 
pandemic, several variants have emerged, causing surges in infection rates despite uptake of 
vaccines. Currently, the SARS-CoV-2 Omicron variant B.1.1.529 and its sublineages are 
dominant globally, though the prevalence of particular sublineages continues to evolve.
Within the US, in late May 2022, the BA.2 and BA.2.12.1 sublineages accounted for the 
majority of sequenced COVID-19 cases, and by mid-August 2022, BA.4 and BA.5 accounted 
for the majority. Substantial immune escape by Omicron BA.4/BA.5 from neutralizing 
antibodies induced by both infection and immunization has been observed, which has been 
attributed to the L452R and F486V spike mutations within the protein sequence of 
BA.4/BA.5. SARS-CoV-2 has continued to evolve with the recombinant XBB sublineages 
dominating within the US and globally by the end of March 2023. The XBB sublineages that 
have become most prevalent have a hallmark F486P mutation that confers further immune 
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escape and host receptor affinity.  The most current weighted estimates from the CDC for the 
2-week period ending on 10 June 2023 for all sequenced cases reported for the Omicron 
sublineages in the US were as follows (those above 3%):  XBB.1.5 (40.0%), XBB.1.16 
(11.8%), XBB.1.9.1 (9.4%), XBB.2.3 (8.5%), XBB.1.16.1 (6.2%), XBB.1.9.2 (5.9%), XBB 
(4.8%), and EG.5 (3.7%).
Moreover, studies have demonstrated that the effectiveness of BNT162b2 against 
SARS-CoV-2 infection and COVID-19 wanes over a period of months, particularly in the 
context of new evolving sublineages.  In light of this waning effectiveness of BNT162b2 as 
well as the existence of subvariants with cumulative mutations in the spike protein, 
development of a new vaccine that could generate an improved immune response, including 
against other variants, could help better protect individuals against COVID-19.
Based on this rationale, Pfizer-BioNTech will evaluate the following vaccine candidates
(original protocol through protocol amendment 2):
Cohort 1: BNT162b5 Bivalent (WT/OMI BA.2), a BNT162b RNA-based vaccine consisting 
of a modified version of the SARS-CoV-2 spike protein mRNA, targeting the ancestral strain 
of the virus, in combination with mRNA encoding the spike protein of the Omicron variant
(BA.2 sublineage).
Cohorts 2 and 3: BNT162b2 Bivalent (WT/OMI BA.4/BA.5) consisting of the original 
SARS-CoV-2 spike protein mRNA, targeting the ancestral strain of the virus, in combination 
with mRNA encoding the spike protein of the Omicron variant (BA.4/BA.5 sublineage).
Multiple real-world studies show that the bivalent (Original/OMI BA.4/BA.5) mRNA 
COVID-19 vaccine provides effective protection against hospitalization and additional 
protection among persons previously vaccinated with only WT-based mRNA vaccine(s).  
However, as the real-world evidence describing bivalent vaccine effectiveness continues to 
accumulate, several reports suggest that vaccine effectiveness against severe illness may 
potentially wane approximately 2 to 4 months after bivalent vaccination, though additional 
data continue to accumulate to better characterize the duration of protection.  In light of early 
evidence of waning effectiveness of the bivalent (Original/OMI BA.4/BA.5) mRNA 
COVID-19 vaccine during periods when the subsequent Omicron sublineages were in 
circulation (BQ.1/BQ.1.1 and XBB/XBB.1.5), development of a more efficacious and 
durable vaccine that could generate an improved, longer-lasting immune response, including 
against current and newly emergent variants and lineages, could help better protect 
individuals against COVID-19.
Based on this rationale, Pfizer-BioNTech will evaluate the following vaccine candidates in 
protocol amendment 6: 
Cohort 4: BNT162b5, BNT162b6, and BNT162b7, new BNT162b RNA-based vaccines
containing different prefusion-stabilized versions of the SARS-CoV-2 spike encoded from
mRNA. Bivalent and/or monovalent formulations targeting the ancestral strain of the virus
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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and/or the Omicron variant (BA.4/BA.5 sublineage) will be evaluated. The Cohort 4 bivalent 
vaccine names use “Original” instead of “Wild Type” (or “WT”).  Both terms refer to the 
ancestral strain (Wuhan-Hu-1; USA-WA1/2020), which is also referred to in this protocol as 
the reference strain.
Objectives, Endpoints, and Estimands:
Objectives
Estimands
Endpoints
Primary Safety
Cohort 1: To describe the safety 
and tolerability profile of 
BNT162b5 Bivalent 
(WT/OMI BA.2) 30 µg and 
BNT162b2 Bivalent 
(WT/OMI BA.1) 30 µg given as a 
second booster dose to COVID-19
vaccine–experienced participants 
18 through 55 years of age.
In participants receiving 1 dose of study 
intervention, the percentage of participants 
reporting:

Local reactions for up to 7 days 
following the study vaccination

Systemic events for up to 7 days 
following the study vaccination

AEs from the study vaccination through 
1 month after the study vaccination

SAEs from the study vaccination 
through 6 months after the study 
vaccination

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
Cohort 2: To describe the safety 
and tolerability profile of 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg 
given as a second booster dose to 
BNT162b2-experienced
participants 12 through 17,
18 through 55, and 55 years of 
age, and BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 60 µg 
given as a second booster dose to 
BNT162b2-experienced 
participants 18 through 55 and 
>55 years of age.
In participants receiving 1 dose of study 
intervention, the percentage of participants 
reporting:

Local reactions for up to 7 days 
following the study vaccination

Systemic events for up to 7 days 
following the study vaccination

AEs from the study vaccination through 
1 month after the study vaccination

SAEs from the study vaccination 
through 6 months after the study 
vaccination

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
Cohort 2 + Cohort 3 combined: 
To describe the safety and 
tolerability profile of BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 
30 µg given as a second booster 
dose to BNT162b2-experienced 
participants 18 through 55 and 
55 years of age.
In participants receiving 1 dose of study 
intervention, the percentage of participants 
reporting:

Local reactions for up to 7 days 
following the study vaccination

Systemic events for up to 7 days 
following the study vaccination

AEs from the study vaccination through 
1 month after the study vaccination

SAEs from the study vaccination 
through 6 months after the study 
vaccination

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
090177e19e249a01\Approved\Approved On: 27-Jul-2023 15:57 (GMT)

PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Objectives
Estimands
Endpoints
Cohort 4a: To describe the safety 
and tolerability profile of 
BNT162b2 Bivalent 30 µg, 
BNT162b5 Bivalent 30 µg,
BNT162b6 Bivalent 30 µg, 
BNT162b7 Bivalent 30 µg, and 
BNT162b7 Monovalent 30 µg 
given to mRNA COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants receiving 1 dose of study 
intervention, the percentage of participants 
reporting:

Local reactions for up to 7 days 
following the study vaccination

Systemic events for up to 7 days 
following the study vaccination

AEs from the study vaccination through 
1 month after the study vaccination

SAEs from the study vaccination 
through 6 months after the study 
vaccination

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
Primary Immunogenicity
Cohort 1: To describe the immune 
response to BNT162b5 Bivalent 
(WT/OMI BA.2) 30 µg and 
BNT162b2 Bivalent 
(WT/OMI BA.1) 30 µg given as a 
second booster dose to COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMT at baseline and 1 month after the 
study vaccination for each strain-
specific neutralizing titer

GMFRs from before the study 
vaccination to 1 month after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron (BA.2)–
neutralizing titers

SARS-CoV-2 
Omicron (BA.1)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 2/Group 4 + Cohort 3/ 
Group 2 combined: To 
demonstrate the superiority with 
respect to level of neutralizing titer 
and noninferiority with respect to 
seroresponse rate of the 
anti-Omicron BA.4/BA.5 immune 
response after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg
compared to after BNT162b2 
30 µgd given as a second booster 
dose to BNT162b2-experienced 
participants >55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMR of the Omicron (BA.4/BA.5)–
neutralizing titers 1 month after 
BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) to 1 month after 
BNT162b2, given as a second booster 
dose in BNT162b2-experienced 
participants

The difference in percentages of 
participants with seroresponse to the 
Omicron BA.4/BA.5 strain at 1 month 
after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) and at 1 month 
after BNT162b2 given as a second 
booster dose in 
BNT162b2-experienced participants

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Objectives
Estimands
Endpoints
Cohort 2/Group 2 + 
Cohort 3/Group 1 combined and 
Cohort 2/Group 4 + Cohort 
3/Group 2 combined: To 
demonstrate the noninferiority 
with respect to level of 
neutralizing titer and with respect 
to seroresponse rate of the 
anti-Omicron BA.4/BA.5 immune 
response after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg
given as a second booster dose to 
BNT162b2-experienced 
participants 18 through 55 years of 
age compared to participants 
>55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMR of the Omicron (BA.4/BA.5)–
neutralizing titers at 1 month after 
BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) given as a second booster 
dose in BNT162b2-experienced 
participants 18 through 55 years of age 
compared to participants >55 years of 
age

The difference in percentages of 
participants with seroresponse to the 
Omicron BA.4/BA.5 strain at 1 month 
after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) given as a 
second booster dose in 
BNT162b2-experienced participants 
18 through 55 years of age compared 
to participants >55 years of age

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers
Cohort 2: To describe the immune 
response to BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg or 
60 µg and BNT162b2 Bivalent 
(WT/OMI BA.1) 30 µge or 60 µge
given as a second booster dose to 
BNT162b2-experienced 
participants 12 through 17, 18 
through 55,e and 55e years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMT at baseline and 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to 1 month after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
Omicron (BA.1)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 4a: To describe the immune 
response to BNT162b2 Bivalent 
30 µg, BNT162b5 Bivalent 30 µg,
BNT162b6 Bivalent 30 µg, 
BNT162b7 Bivalent 30 µg, and 
BNT162b7 Monovalent 30 µg 
given to mRNA COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMT at baseline and 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to 1 month after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Objectives
Estimands
Endpoints
Secondary Immunogenicity
Cohort 2/Group 4 + 
Cohort 3/Group 2 combined: To 
demonstrate the noninferiority of 
the anti–reference-strain immune 
response after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg
compared to BNT162b2 30 µgd
given as a second booster dose in 
BNT162b2-experienced 
participants >55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMR of the reference-strain–
neutralizing titers at 1 month after 
BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) and at 1 month after 
BNT162b2 given as a second booster 
dose in BNT162b2-experienced 
participants

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 2/Group 2 + Cohort 
3/Group 1 combined and Cohort 
2/Group 4 + Cohort 3/Group 2 
combined: To describe the 
immune response to BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 
30 µg compared to BNT162b2 
30 µgd given as a second booster 
dose to BNT162b2-experienced 
participants 18 through 55 and 
>55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMT at baseline and 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to 1 month after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Exploratory
Cohort 1: To describe the immune 
response to BNT162b5 Bivalent
(WT/OMI BA.2) 30 µg and 
BNT162b2 Bivalent 
(WT/OMI BA.1) 30 µg given as a 
second booster dose to COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants): 
At baseline and 7 days, 1 month, 3 months,
and 6 months after study vaccination,

GMT at each time point for each 
strain-specific neutralizing titer

GMFRs from before the study 
vaccination to each time point after the 
study vaccination for each 
strain-specific neutralizing titer

Percentages of participants with 
seroresponseb at each time point after 
the study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron (BA.2)–
neutralizing titers

SARS-CoV-2 
Omicron (BA.1)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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TMF Doc ID: 164.01
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Objectives
Estimands
Endpoints
Cohort 2/Group 1, Cohort 2/Group 
2 + Cohort 3/Group 1 combinedf  
Cohort 2/Group 4 + 
Cohort 3/Group 2 combinedf
Cohort 2/Group 3, and Cohort 
2/Group 5: To describe the 
immune response to BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 
30 µg or 60 µg compared to 
BNT162b2 30 µgf given as a 
second booster dose to 
BNT162b2-experienced 
participants 12 through 17, 
18 through 55, and >55 years of 
age.
In participants complying with the key 
protocol criteria (evaluable participants):
At baseline and 1 month, 3 months, and 6 
months after the study vaccination,

GMT at each time point for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to each subsequent time 
point for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at each time point 
following vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 4a: To describe the immune 
response to BNT162b2 Bivalent 
30 µg, BNT162b5 Bivalent 30 µg,
BNT162b6 Bivalent 30 µg, 
BNT162b7 Bivalent 30 µg, and 
BNT162b7 Monovalent 30 µg 
given to mRNA COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):
At baseline and 7 days, 1 month, 3 months,
and 6 months after the study vaccination,

GMT at each time point for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to each time point after the 
study vaccination for each strain-
specific neutralizing titer

Percentages of participants with 
seroresponseb at each time point after 
the study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 1, Cohort 2 + Cohort 3 
combined, and Cohort 4: To 
describe confirmed COVID-19 
and severe COVID-19 cases in 
each vaccine group and age group.

Confirmed COVID-
19 cases

Confirmed severe 
COVID-19 cases

Strain sequencing of 
COVID-19 cases
Cohort 1, Cohort 2 + Cohort 3 
combined, and Cohort 4: To 
describe the immune response to 
SARS-CoV-2 infection at the time 
of the COVID-19 illness visitg and 
at the convalescent visit.

SARS-CoV-2–
neutralizing titers 
previously specified 
for the respective 
cohorts
Cohort 1, Cohort 2 + Cohort 3 
combined, and Cohort 4: To 
describe the immune response to 
other emerging variants (under 
monitoring, of interest, and/or of 
concern).

SARS-CoV-2–
neutralizing titers for 
other variants (under 
monitoring, of 
interest, and/or of 
concern) not already 
specified
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Objectives
Estimands
Endpoints
Cohort 2: To describe the 
cell-mediated immune response, 
and additional humoral immune 
response parameters, to the 
reference strainc and Omicron 
variant in a subset of participants 
with PBMC samples collected.
a.
The Cohort 4 bivalent vaccines target the SARS-CoV-2 Original strain and the Omicron variant
(BA.4/BA.5 sublineage).  The Cohort 4 monovalent vaccine targets the Omicron variant (BA.4/BA.5 
sublineage).
b.
Seroresponse is defined as achieving a ≥4-fold rise from the baseline (before the study vaccination).  If 
the baseline measurement is below the LLOQ, the postvaccination measure of ≥4 × LLOQ is considered 
seroresponse.
c.
Reference strain is also referred to as the Original, Wild Type, or ancestral strain (Wuhan-Hu-1; 
USA-WA1/2020).
d.
The participants >55 years of age from C4591031 Substudy E expanded cohort who received BNT162b2 
30 µg as a second booster dose will be used as comparator group for this objective.
e.
A subset of approximately 100 participants in each age group (18 through 55 years of age, >55 years of 
age) and dose group (30 µg, 60 µg) from C4591031 Substudy E expanded cohort who received Bivalent 
BNT162b2 (WT/OMI BA.1) 30 µg or 60 µg as a second booster dose will be randomly selected for this 
objective. The subset selected from C4591031 Substudy E will include a similar percentage of 
participants with baseline positive SARS-CoV-2 infection status as the groups in Cohort 2 of this study 
whenever feasible.
f.
A subset of approximately 100 participants in each age group (18 through 55 years of age, >55 years of 
age) from C4591044 Cohort 2/Group 2 + Cohort 3/Group 1 combined and Cohort 2/Group 4 + 
Cohort 3/Group 2 combined who received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg and from 
the C4591031 Substudy E expanded cohort who receive BNT162b2 30 µg as a second booster dose will 
be selected for this objective. The subset selected will include a similar percentage of participants with 
baseline positive SARS-CoV-2 infection status whenever feasible.
g.
If the COVID-19 illness visit is conducted as an in-person visit, a blood sample will be taken for this 
assessment. No blood samples will be obtained for remote (telehealth) COVID-19 illness visits.
Overall Design:
This study is a randomized, active-controlled study to evaluate the safety, tolerability, and 
immunogenicity of new bivalent and monovalent vaccines. The study vaccine candidates are 
divided into cohorts, which may be studied in a staggered or parallel manner, as required by 
the clinical plan.
Cohort 1: Participants 18 through 55 years of age will be randomized at a ratio of 1:1 to 
receive a single 30-µg dose of either BNT162b5 Bivalent (WT/OMI BA.2) or BNT162b2 
Bivalent (WT/OMI BA.1) as a second booster dose. Participants will be stratified by the 
number of months since the last dose of the COVID-19 vaccine received prior to 
randomization (3 to 6 months [90 to 180 days] or >6 months [>180 days]).
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Cohort 2: Participants 12 through 17 years of age who have received 3 prior doses of 
BNT162b2 (30-µg doses), with the most recent dose being 150 to 365 days prior to Visit 1
(Day 1), will receive a single 30-µg dose of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) as a 
second booster dose (open-label). Participants 18 through 55 years of age and 55 years of 
age who have received 3 prior doses of BNT162b2 (30-µg doses), with the most recent dose 
being 150 to 365 days prior to Visit 1 (Day 1), will be randomized 1:1 within each age group 
to receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at either 30 µg or 60 µg as a second 
booster dose (observer-blind).
Cohort 2: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
Group
Participant Age 
Group
Prior Doses of 
BNT162b2
Time Since 
Last Dose
Study
Dose
Number of 
Participants
Randomization /
Blind
1
12-17 years
3
150-365 days
30 µg
100
Open-label
2
18-55 years
3
150-365 days
30 µg
100
Randomized 1:1
Observer-blind
3
18-55 years
3
150-365 days
60 µg
100
4
55 years
3
150-365 days
30 µg
100
Randomized 1:1
Observer-blind
5
55 years
3
150-365 days
60 µg
100
Cohort 3: Participants 18 years of age and older who have received 3 prior 30-µg doses of 
BNT162b2, with the most recent dose being 150 to 365 days prior to Visit 1 (Day 1), will 
receive a single 30-µg dose of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) as a second 
booster dose (open-label).
Cohort 3: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
Group
Participant Age 
Group
Prior Doses of 
BNT162b2
Time Since 
Last Dose
Study 
Dose
Number of 
Participants
Randomization / 
Blind
1
18-55 years
3
150-365 days
30 µg
200
Open-label
2
55 years
3
150-365 days
30 µg
200
Open-label
Cohort 4: Participants 18 through 55 years of age who have received 3 or 4 prior doses of a 
US-authorized mRNA COVID-19 vaccine, with the most recent dose being a bivalent 
vaccine at least 150 days prior to Visit 1 (Day 1), will be enrolled. The Cohort 4 bivalent 
vaccines target the SARS-CoV-2 Original strain and the Omicron variant 
(BA.4/BA.5 sublineage).  The Cohort 4 monovalent vaccine targets the Omicron variant 
(BA.4/BA.5 sublineage).  Participants will be randomized at a ratio of 1:1:1:1:1 to receive a 
single 30-µg dose of either BNT162b2 Bivalent, BNT162b5 Bivalent, BNT162b6 Bivalent, 
BNT162b7 Bivalent, or BNT162b7 Monovalent (observer-blind).  Participants will be 
stratified by the number of prior doses (3 or 4 prior doses) of a US-authorized mRNA 
COVID-19 vaccine received prior to randomization.
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Page 21
Cohort 4: BNT162b Omicron BA.4/BA.5 Vaccine Candidates
All Participants 18 Through 55 Years of Age
Group
Study Intervention
Study 
Dose
Prior Doses 
of mRNA 
COVID-19 
Vaccine 
Time 
Since 
Last Dose
Number of 
Participants
Randomization / 
Blind
1
BNT162b2 Bivalent 
(Original/OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
Randomized
1:1:1:1:1
Observer-blind
2
BNT162b5 Bivalent 
(Original/OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
3
BNT162b6 Bivalent 
(Original/OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
4
BNT162b7 Bivalent 
(Original/OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
5
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
Number of Participants:
Cohort 1: Approximately 200 participants will be enrolled.
Cohort 2: Approximately 500 participants will be enrolled.
Cohort 3: Approximately 400 participants will be enrolled.
Cohort 4: Approximately 300 participants will be enrolled.
Study Population:
The inclusion and exclusion criteria are listed below:
Inclusion Criteria 
Participants must meet the following inclusion criteria to be eligible for enrollment into the 
study:
1. Ages for each cohort as follows:
Cohort 1: Participants 18 through 55 years of age at randomization.  
Cohort 2: Participants ≥12 years of age at Visit 1.
Cohort 3: Participants ≥18 years of age at Visit 1.
Cohort 4: Participants 18 through 55 years of age at Visit 1.
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
Refer to the body of the protocol for reproductive criteria for male and female 
participants.
Participant and Disease Characteristics:
2. Participants and participants’ parent(s)/legal guardian(s), as appropriate, willing and able 
to comply with all scheduled visits/contacts, investigational plan, laboratory tests, and 
other study procedures.
3. Healthy participants who are determined by medical history, physical examination
(if indicated), 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. 
Informed Consent:
4. Capable of giving signed informed consent, which includes compliance with the 
requirements and restrictions listed in the ICD and in this protocol.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each study participant’s legal guardian and the participant’s assent, when 
applicable, before any study-specific activity is performed. All legal guardians should 
be fully informed, and participants should be informed to the fullest extent possible, 
about the study in language and terms they are able to understand. The investigator will 
retain the original copy of each participant's signed consent/assent document.
Other Inclusion Criteria:
5. Cohort 1: Participants who have received 1 booster dose of a US-authorized COVID-19 
vaccine, with the last prior dose being 90 or more days before Visit 1 (Day 1).
Note: Documented confirmation of prior COVID-19 vaccines received must be obtained 
prior to randomization.  All prior COVID-19 vaccines must be authorized for use in the 
US.
Cohort 2 and Cohort 3: Participants who have received 3 prior 30-µg doses of 
BNT162b2, with the last dose being 150 to 365 days before Visit 1 (Day 1). 
Note: Documented confirmation of prior doses of BNT162b2 received must be obtained 
prior to randomization.
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Cohort 4: Participants who have received 3 or 4 prior doses of a US-authorized mRNA 
COVID-19 vaccine (and dose level), with the last dose being a US-authorized Omicron 
BA.4/BA.5–adapted bivalent vaccine and dose level at least 150 days before Visit 1 
(Day 1).
Note: Documented confirmation of prior mRNA COVID-19 vaccines received must be 
obtained before randomization. Participants must have received mRNA COVID-19 
vaccines only.
Exclusion Criteria
Participants with any of the following characteristics/conditions will be excluded:
Medical Conditions:
1. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study intervention(s).
2. Immunocompromised individuals with known or suspected immunodeficiency, as 
determined by history and/or laboratory/physical examination.
3. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
4. Women who are pregnant or breastfeeding.
5. Other medical or psychiatric condition, including recent (within the past year) or active 
suicidal ideation/behavior, or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the 
study.
Prior/Concomitant Therapy:
6. Receipt of chronic systemic treatment with known immunosuppressant medications 
(including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune 
disease), or radiotherapy, within 60 days before enrollment or planned receipt through 
conclusion of the study.
Note: Chronic systemic corticosteroids are defined as those administered for ≥14 days at 
a dose of ≥20 mg/day of prednisone or equivalent. Inhaled/nebulized, intra-articular, 
intrabursal, or topical (skin or eyes) corticosteroids are permitted.
7. 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 60 days before study intervention administration or planned 
receipt throughout the study.
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Prior/Concurrent Clinical Study Experience:
8. Participation in other studies involving receipt of a study intervention within 28 days 
before randomization. Anticipated participation in other studies involving a study 
intervention from randomization through the end of this study.
Other Exclusion Criteria:
9. 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.
Other Medical Conditions: From protocol amendment 6 (Cohort 4) onwards:
10. History of myocarditis or pericarditis.
Study Arms and Duration:
The study duration for each participant will be approximately 6 months. For the purposes of 
this protocol, study intervention refers to: 
Cohort 1

BNT162b5 Bivalent (WT/OMI BA.2) =
BNT162b5 Wild Type and BNT162b5 OMICRON (B.1.1.529) sublineage BA.2
(BNT162b5 RNA-LNP vaccine utilizing modRNA and encoding the P6’ S)

BNT162b2 Bivalent (WT/OMI BA.1) =
BNT162b2 Wild Type and BNT162b2 OMICRON (B.1.1.529) sublineage BA.1
(BNT162b2 RNA-LNP vaccine utilizing modRNA and encoding the P2 S)
Study Interventions – Cohort 1
Intervention Name
BNT162b5 Bivalent (WT/OMI BA.2)
(BNT162b5 Wild Typea and 
BNT162b5 OMICRON 
[B.1.1.529 sublineage BA.2])
Preformulated as a single vial 
(no dilution required)
BNT162b2 Bivalent (WT/OMI BA.1)
(BNT162b2 Wild Typea and 
BNT162b2 OMICRON
[B.1.1.529 sublineage BA.1])
Preformulated as a single vial 
(no dilution required)
Arm Name
(group of participants 
receiving a specific study 
intervention or no study 
intervention)
BNT162b5 Bivalent (WT/OMI BA.2)
BNT162b2 Bivalent (WT/OMI BA.1)
Unit Dose Strength(s)
100 µg/mL
100 µg/mL
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Study Interventions – Cohort 1
Dosage Level(s)
30 µg 
(15 µg BNT162b5 Wild Type and
15 µg BNT162b5 OMICRON 
[B.1.1.529 sublineage BA.2])
30 µg 
(15 µg BNT162b2 Wild Type and
15 µg BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.1])
Route of Administration
Intramuscular injection
Intramuscular injection
Use
Experimental 
Experimental and active comparator 
IMP or NIMP/AxMP
IMP
IMP
a.
Wild Type refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol 
as the Original or reference strain.
Study Arms – Cohort 1
Arm Title
BNT162b5 Bivalent (WT/OMI BA.2)
BNT162b2 Bivalent (WT/OMI BA.1)
Arm Type
Experimental
Experimental and active comparator
Arm Description
Participants will receive 30 µg of 
BNT162b5 Bivalent (WT/OMI BA.2)
at Visit 1.
Participants will receive 30 µg of 
BNT162b2 Bivalent (WT/OMI BA.1)
at Visit 1.
Cohort 2

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) =
BNT162b2 Wild Type and BNT162b2 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b2 RNA-LNP vaccine utilizing modRNA and encoding the P2 S)
Study Interventions – Cohort 2
Intervention Name
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 
(BNT162b2 Wild Typea and BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.4/BA.5])
Preformulated as a single vial (no dilution required)
Arm Name (group of 
participants receiving a specific 
study intervention or no study 
intervention)
BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
Unit Dose Strength(s)
100 µg/mL
Dosage Level(s)
30 µg or 60 µg
(15 µg BNT162b2 Wild Type and 15 µg BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.4/BA.5])
(30 µg BNT162b2 Wild Type and 30 µg BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.4/BA.5])
Route of Administration
Intramuscular injection
Use
Experimental 
IMP or NIMP/AxMP
IMP
a.
Wild Type refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020); it is also referred to in this 
protocol as the Original or reference strain.
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Study Arms – Cohort 2
Arm Title
Group 1:
12-17 years, 
30 µg
Group 2: 
18-55 years, 
30 µg
Group 3:
18-55 years, 
60 µg
Group 4:
55 years, 
30 µg
Group 5:
>55 years, 
60 µg
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm 
Description
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
30 µg
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
30 µg
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
60 µg
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5)
30 µg
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
60 µg
Cohort 3

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) =
BNT162b2 Wild Type and BNT162b2 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b2 RNA-LNP vaccine utilizing modRNA and encoding the P2 S)
Study Interventions – Cohort 3
Intervention Name
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 
(BNT162b2 Wild Typea and BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.4/BA.5])
Preformulated as a single vial (no dilution required)
Arm Name 
(group of participants receiving a specific study 
intervention or no study intervention)
BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
Unit Dose Strength(s)
100 µg/mL
Dosage Level(s)
30 µg 
(15 µg BNT162b2 Wild Type and 
15 µg BNT162b2 OMICRON [B.1.1.529 sublineage 
BA.4/BA.5])
Route of Administration
Intramuscular injection
Use
Experimental 
IMP or NIMP/AxMP
IMP
a.
Wild Type refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020); it is also referred to in this 
protocol as the Original or reference strain.
Study Arms – Cohort 3
Arm Title
Group 1: 18-55 years, 30 µg
Group 2: >55 years, 30 µg
Arm Type
Experimental
Experimental 
Arm Description
Participants will receive BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 30 µg 
at Visit 1
Participants will receive BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 30 µg 
at Visit 1
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Cohort 4
The Cohort 4 bivalent vaccine names use “Original” instead of “Wild Type” (or “WT”).  
Both terms refer to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), which is also 
referred to in this protocol as the reference strain. Study intervention labeling may contain 
“Wild Type/WT” or “Original” interchangeably. 

BNT162b2 Bivalent (Original/OMI BA.4/BA.5) =
BNT162b2 Original and BNT162b2 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b2 RNA-LNP vaccine utilizing modRNA and encoding the P2 S)

BNT162b5 Bivalent (Original/OMI BA.4/BA.5) =
BNT162b5 Original and BNT162b5 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b5 RNA-LNP vaccine utilizing modRNA and encoding the P6’ S)

BNT162b6 Bivalent (Original/OMI BA.4/BA.5) =
BNT162b6 Original and BNT162b6 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b6 RNA-LNP vaccine utilizing modRNA for the P6 S)

BNT162b7 Bivalent (Original/OMI BA.4/BA.5) =
BNT162b7 Original and BNT162b7 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b7 RNA-LNP vaccine utilizing modRNA for the P6 S)

BNT162b7 Monovalent (OMI BA.4/BA.5) =
BNT162b7 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b7 RNA-LNP vaccine utilizing modRNA for the P6 S)
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Study Interventions – Cohort 4
Intervention Name
BNT162b2 Bivalent 
(Original/OMI 
BA.4/BA.5)
(BNT162b2 Originala and 
BNT162b2 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
Preformulated in a single 
vial (no dilution required)
BNT162b5 Bivalent 
(Original/OMI 
BA.4/BA.5)
(BNT162b5 Originala and 
BNT162b5 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
Preformulated in a single 
vial (no dilution required)
BNT162b6 Bivalent 
(Original/OMI 
BA.4/BA.5)
(BNT162b6 Originala and 
BNT162b6 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5]) 
Preformulated in a single 
vial (no dilution required)
BNT162b7 Bivalent 
(Original/OMI 
BA.4/BA.5)
(BNT162b7 Originala and 
BNT162b7 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
Preformulated in a single 
vial (no dilution required)
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
(BNT162b7 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
Preformulated in a single 
vial (no dilution required)
Arm Name
(group of participants 
receiving a specific 
study intervention or no 
study intervention)
BNT162b2 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b5 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b6 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b7 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
Unit Dose Strength(s)
100 µg/mL
100 µg/mL
100 µg/mL
100 µg/mL
100 µg/mL
Dosage Level(s)
30 µg 
(15 µg BNT162b2 
Original and 15 µg 
BNT162b2 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
30 µg 
(15 µg BNT162b5 
Original and 15 µg 
BNT162b5 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
30 µg 
(15 µg BNT162b6 
Original and 15 µg 
BNT162b6 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
30 µg 
(15 µg BNT162b7 
Original and 15 µg 
BNT162b7 OMICRON
[B.1.1.529 sublineage 
BA.4/BA.5])
30 µg 
(30 µg BNT162b7 
OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
Route of Administration Intramuscular injection
Intramuscular injection
Intramuscular injection
Intramuscular injection
Intramuscular injection
Use
Active comparator 
Experimental
Experimental
Experimental
Experimental
IMP or NIMP/AxMP
IMP
IMP
IMP
IMP
IMP
a.
Original refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol as Wild Type, WT, and the reference strain.  Study 
intervention vial labels for the Cohort 4 bivalent vaccines may specify WT instead of Original.
Study Arms – Cohort 4
Arm Title
BNT162b2 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b5 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b6 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b7 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
Arm Type
Active comparator 
Experimental
Experimental
Experimental
Experimental
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Statistical Methods:
Cohorts 1, 2, and 4: 
For the objectives evaluated separately within Cohort 1, Cohort 2, and Cohort 4, the sample 
size is not based on any statistical hypothesis testing since all objectives are descriptive.  The 
primary safety objective will be evaluated by descriptive summary statistics for local 
reactions, systemic events, and AEs/SAEs for each vaccine group.  The primary 
immunogenicity objectives will be evaluated descriptively by GMT, GMFR, and percentage 
of participants with seroresponse of SARS-CoV-2–neutralizing titers at the various time 
points.
Cohort 2 + Cohort 3 combined:
The primary safety objective will be evaluated by descriptive summary statistics for local 
reactions, systemic events, and AEs/SAEs for each age group.
For the >55-year age group, the primary immunogenicity objective will be evaluated by 
GMR of the Omicron BA.4/BA.5–neutralizing titers and difference in percentage of 
participants with seroresponse to the Omicron BA.4/BA.5 strain induced by BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) relative to BNT162b2 at 1 month after the study 
vaccination.  The BNT162b2 group is a historic comparator, from approximately 300 
participants >55 years of age who received BNT162b2 30 µg as a fourth dose in C4591031 
Substudy E expanded cohort, after 3 prior 30-µg doses of BNT162b2. Assuming a 
20% nonevaluable rate, with approximately 300 participants to receive BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) in this study and approximately 300 participants who received 
BNT162b2 from C4591031 Substudy E, there will be approximately 480 evaluable 
participants (240 BNT162b2 Bivalent [WT/OMI BA.4/BA.5] and 240 BNT162b2)
contributing to the immunogenicity evaluation. Superiority based on GMR will be declared if 
the lower limit of the 2-sided 95% CI for the GMR is greater than 1; noninferiority based on 
seroresponse will be declared if the lower limit of the 2-sided 95% CI for the difference in 
percentages of participants with seroresponse is >-5%.
For the 18- through 55-year age group, the primary immunogenicity objective will be 
evaluated by GMR of the Omicron BA.4/BA.5–neutralizing titers and difference in 
percentage of participants with seroresponse to the Omicron BA.4/BA.5 strain induced by 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) relative to BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) in the >55-year age group at 1 month after the study vaccination. Assuming a 
20% nonevaluable rate, with approximately 300 participants to receive BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) in each age group, there will be approximately 480 evaluable 
participants (240 in the 18- through 55-year age group and 240 in the >55-year age group)
contributing to the immunogenicity evaluation. Noninferiority based on GMR will be 
declared if the lower limit of the 2-sided 95% CI for the GMR is greater than 0.67; 
noninferiority based on seroresponse will be declared if the lower limit of the 2-sided 95% CI 
for the difference in percentages of participants with seroresponse is >-10%.
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The secondary immunogenicity objective for the >55-year age group will be evaluated by 
GMR of the reference-strain–neutralizing titers induced by BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) relative to BNT162b2 (historic comparator) at 1 month after the study 
vaccination. Noninferiority based on the GMR will be declared if the lower limit of the 
2-sided 95% CI for the GMR is greater than 0.67 (1.5-fold criterion) and the point estimate of 
the GMR is ≥0.8.
The primary objective for the >55-year age group will be evaluated first, followed by the 
secondary objective for GMR in the >55-year age group and then the primary objective for 
the 18-through 55-year age group. Each of these objectives will be evaluated only if the 
previous objective is met. Each primary objective involves 2 hypotheses: GMR and 
seroresponse rate difference. Both hypotheses within the objective must be established 
before evaluating the next objective in the sequence. Therefore, the overall type I error is 
fully controlled.
The other secondary immunogenicity objectives will be evaluated descriptively by GMT, 
GMFR, the difference in percentages of participants with seroresponse, and the associated 
95% CIs for SARS-CoV-2–neutralizing titers at the various time points.
Ethical Considerations:
The available safety and immunogenicity data from ongoing Pfizer-BioNTech clinical trials 
and real-world effectiveness and safety data, combined with available nonclinical data with 
BNT162b vaccines and data from nonclinical and clinical trials with the same or related 
RNA components or antigens, support a favorable benefit/risk profile and support clinical 
development of BNT162b2, BNT162b5, BNT162b6, and BNT162b7 bivalent vaccines, and 
of BNT162b7 monovalent vaccine. Taking into account the measures to minimize risk to 
study participants, the potential risks identified in association with the study intervention are 
justified by the anticipated benefits that may be afforded to healthy participants.

As all vaccines under study use the same modRNA platform and LNP formulation as 
BNT162b2, their safety profiles are expected to be similar to that of BNT162b2.  Based 
on the experience with BNT162b2, the potential risks for BNT162b2 include the 
following:

Local reactions, such as injection site redness, injection site swelling, and injection 
site pain, and systemic events, such as fever, fatigue, headache, chills, muscle pain, 
and joint pain.

Very rare cases of myocarditis and pericarditis have been reported after authorization 
in recipients of BNT162b2.

Cases of anaphylaxis have been reported; however, the frequency is not estimable 
from the available data.
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
The study procedure–related risks include:

Original protocol and amendments 1 and 2: Participants will be required to attend 
healthcare facilities during the global SARS-CoV-2 pandemic.

Venipuncture will be performed during the study.

Participants will be expected to commit time and may experience some discomfort while 
undergoing study assessments.
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1.2. Schema
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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. 
An unplanned potential COVID-19/MIS-C illness visit and unplanned potential COVID-19/MIS-C convalescent visit are required at 
any time between Visit 1 (vaccination) and Visit 5 (6-month follow-up visit) that COVID-19 symptoms are reported. During the 
7 days following each dose, potential COVID-19/MIS-C symptoms that overlap with specific systemic events (ie, fever, chills, new or 
increased muscle pain, diarrhea, vomiting) should not trigger a potential COVID-19/MIS-C illness visit unless, in the investigator’s 
opinion, the clinical picture is more indicative of a possible COVID-19/MIS-C illness rather than vaccine reactogenicity. For details, 
see Section 8.10.7.
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. Based on review of safety or immunogenicity data of any study 
intervention group, at Pfizer’s discretion, study visits, blood sample collection/analysis, or other procedures may be halted or 
discontinued.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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TMF Doc ID: 164.01
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Notes
Visit Identifier
1
2
3
4
5
Unplanned
Unplanned
Visit Description
Vax 1 
Visit
1-Week 
Follow-Up 
Visit
(Vax 1)
1-Month 
Follow-Up 
Visit
(Vax 1)
3-Month 
Follow-Up 
Visit
(Vax 1)
6-Month 
Follow-Up 
Visit
(Vax 1)
Potential 
COVID-19
Illness Visit
Potential 
COVID-19 
Convalescent 
Visit
The COVID-19 illness visit 
may be conducted as an 
in-person or telehealth 
visit.
The COVID-19 illness visit 
is only conducted for 
symptomatic participants. 
See Section 8.10.7.
Visit Window
Day 1
6 to 8 Days 
After 
Visit 1
28 to 35 
Days After 
Visit 1
84 to 98 
Days After 
Visit 1
175 to 189 
Days After 
Visit 1
Optimally 
Within 3 Days 
After 
Potential 
COVID-19 
Illness Onset
28 to 35 Days 
After 
Potential 
COVID-19 
Illness Visit
Obtain informed consent and assent 
(if appropriate)
X
If vaccination is temporarily 
delayed, per Section 5.5, 
consent need not be obtained 
again on the day of 
vaccination.
Assign participant number 
X
If participant is from a prior 
Pfizer COVID-19 study, 
record the participant 
number of the prior study in 
the CRF. If more than 1
study, record the participant 
number of both the most 
recent prior study and the 
first study.
Obtain demography and medical history data 
(including confirmed COVID-19 diagnosis 
or asymptomatic positive SARS-CoV-2 test 
result)
X
Obtain documentation of all prior COVID-19 
vaccines
X
Record details in the prior 
COVID-19 vaccination 
CRF.
Urine pregnancy test (if appropriate)
X
Refer to Section 8.3.5.
Confirm use of contraceptives 
(if appropriate)
X
X
X
Refer to Section 5.3.1.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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TMF Doc ID: 164.01
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Notes
Visit Identifier
1
2
3
4
5
Unplanned
Unplanned
Visit Description
Vax 1 
Visit
1-Week 
Follow-Up 
Visit
(Vax 1)
1-Month 
Follow-Up 
Visit
(Vax 1)
3-Month 
Follow-Up 
Visit
(Vax 1)
6-Month 
Follow-Up 
Visit
(Vax 1)
Potential 
COVID-19
Illness Visit
Potential 
COVID-19 
Convalescent 
Visit
The COVID-19 illness visit 
may be conducted as an 
in-person or telehealth 
visit.
The COVID-19 illness visit 
is only conducted for 
symptomatic participants. 
See Section 8.10.7.
Visit Window
Day 1
6 to 8 Days 
After 
Visit 1
28 to 35 
Days After 
Visit 1
84 to 98 
Days After 
Visit 1
175 to 189 
Days After 
Visit 1
Optimally 
Within 3 Days 
After 
Potential 
COVID-19 
Illness Onset
28 to 35 Days 
After 
Potential 
COVID-19 
Illness Visit
Measure height and weight 
X
Perform clinical assessment
X
X
X
X
X
Including, if indicated, a 
physical examination 
(Section 8.3.1).
Record nonstudy vaccine information
X
X
X
X
X
Refer to Section 6.9.
Record prohibited medication use
X
X
X
X
X
X
Refer to Section 6.9.1.
Confirm eligibility
X
Measure body temperature
X
Review temporary delay criteria
X
Nasal (midturbinate) swab for SARS-CoV-2 
NAAT 
X
X
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
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Notes
Visit Identifier
1
2
3
4
5
Unplanned
Unplanned
Visit Description
Vax 1 
Visit
1-Week 
Follow-Up 
Visit
(Vax 1)
1-Month 
Follow-Up 
Visit
(Vax 1)
3-Month 
Follow-Up 
Visit
(Vax 1)
6-Month 
Follow-Up 
Visit
(Vax 1)
Potential 
COVID-19
Illness Visit
Potential 
COVID-19 
Convalescent 
Visit
The COVID-19 illness visit 
may be conducted as an 
in-person or telehealth 
visit.
The COVID-19 illness visit 
is only conducted for 
symptomatic participants. 
See Section 8.10.7.
Visit Window
Day 1
6 to 8 Days 
After 
Visit 1
28 to 35 
Days After 
Visit 1
84 to 98 
Days After 
Visit 1
175 to 189 
Days After 
Visit 1
Optimally 
Within 3 Days 
After 
Potential 
COVID-19 
Illness Onset
28 to 35 Days 
After 
Potential 
COVID-19 
Illness Visit
Blood sample for immunogenicity 
assessment
~50 mL / 
10 mL
~20 mL / 
10 mL
~50 mL / 
10 mL
~20 mL / 
10 mL
~20 mL / 
10 mL
~20 mL / 
10 mL*
~20 mL / 
10 mL
50 mL/20 mL is to be 
collected from participants 
≥18 years of age; 10 mL is 
to be collected from 
participants 12 through
17 years of age.
*If the Potential COVID-19 
Illness Visit is an in-person
visit, a blood sample will be 
taken.
Blood sample collection may 
be halted or discontinued 
upon notification by Pfizer.
Blood sample for PBMC isolation
~130 mL
~130 mL
~130 mL
~130 mL
~130 mL
Applicable at designated 
sites only with optional 
consent given by participants 
≥18 years of age. See 
Section 8.2.2. Not
applicable to Cohort 1, 
Cohort 3, or Cohort 4.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Final Protocol Amendment 6, 27 Jul 2023
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 37
Notes
Visit Identifier
1
2
3
4
5
Unplanned
Unplanned
Visit Description
Vax 1 
Visit
1-Week 
Follow-Up 
Visit
(Vax 1)
1-Month 
Follow-Up 
Visit
(Vax 1)
3-Month 
Follow-Up 
Visit
(Vax 1)
6-Month 
Follow-Up 
Visit
(Vax 1)
Potential 
COVID-19
Illness Visit
Potential 
COVID-19 
Convalescent 
Visit
The COVID-19 illness visit 
may be conducted as an 
in-person or telehealth 
visit.
The COVID-19 illness visit 
is only conducted for 
symptomatic participants. 
See Section 8.10.7.
Visit Window
Day 1
6 to 8 Days 
After 
Visit 1
28 to 35 
Days After 
Visit 1
84 to 98 
Days After 
Visit 1
175 to 189 
Days After 
Visit 1
Optimally 
Within 3 Days 
After 
Potential 
COVID-19 
Illness Onset
28 to 35 Days 
After 
Potential 
COVID-19 
Illness Visit
Blood sample for HLA typing
~5 mL
Applicable at designated 
sites only with optional 
consent given by participants 
≥18 years of age. See 
Section 8.2.2. Not
applicable to Cohort 1, 
Cohort 3, or Cohort 4.
Obtain randomization number using the IRT 
system
X
Obtain the participant’s vaccine vial 
allocation using the IRT system
X
Administer study intervention
X
Refer to Section 6.1.1
Assess acute reactions for at least 30 minutes 
after study intervention administration
X
Explain participant communication methods 
(including for COVID-19 illness and 
reactogenicity e-diary completion and severe 
reactogenicity symptoms), assist the 
participant or participant’s parent(s)/legal 
guardian with downloading the app or issue 
provisioned device, if required 
X
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TMF Doc ID: 164.01
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Notes
Visit Identifier
1
2
3
4
5
Unplanned
Unplanned
Visit Description
Vax 1 
Visit
1-Week 
Follow-Up 
Visit
(Vax 1)
1-Month 
Follow-Up 
Visit
(Vax 1)
3-Month 
Follow-Up 
Visit
(Vax 1)
6-Month 
Follow-Up 
Visit
(Vax 1)
Potential 
COVID-19
Illness Visit
Potential 
COVID-19 
Convalescent 
Visit
The COVID-19 illness visit 
may be conducted as an 
in-person or telehealth 
visit.
The COVID-19 illness visit 
is only conducted for 
symptomatic participants. 
See Section 8.10.7.
Visit Window
Day 1
6 to 8 Days 
After 
Visit 1
28 to 35 
Days After 
Visit 1
84 to 98 
Days After 
Visit 1
175 to 189 
Days After 
Visit 1
Optimally 
Within 3 Days 
After 
Potential 
COVID-19 
Illness Onset
28 to 35 Days 
After 
Potential 
COVID-19 
Illness Visit
Provide thermometer and measuring device
X
Provide/ensure the participant has a nasal 
self-swab kit and instructions on 
self-collection (or collection by parent/legal 
guardian) of nasal swabs
X
X
X
X
Ask/remind the participant or participant’s 
parent(s)/legal guardian to contact the site if 
participant experiences any severe 
(Grade 3) reactogenicity symptoms 
X
X
Ask/remind the participant or participant’s 
parent(s)/legal guardian to contact the site if 
a medically attended event or hospitalization 
occurs
X
X
X
X
Ask/remind the participant or participant’s 
parent(s)/legal guardian to contact site 
immediately if participant experiences any 
symptoms as detailed in Section 8.10.7
(COVID-19/MIS-C surveillance)
X
X
X
X
Participant completes COVID-19 illness 
e-diary
Refer to Section 8.2 and 
Section 8.10.7.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Final Protocol Amendment 6, 27 Jul 2023
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 39
Notes
Visit Identifier
1
2
3
4
5
Unplanned
Unplanned
Visit Description
Vax 1 
Visit
1-Week 
Follow-Up 
Visit
(Vax 1)
1-Month 
Follow-Up 
Visit
(Vax 1)
3-Month 
Follow-Up 
Visit
(Vax 1)
6-Month 
Follow-Up 
Visit
(Vax 1)
Potential 
COVID-19
Illness Visit
Potential 
COVID-19 
Convalescent 
Visit
The COVID-19 illness visit 
may be conducted as an 
in-person or telehealth 
visit.
The COVID-19 illness visit 
is only conducted for 
symptomatic participants. 
See Section 8.10.7.
Visit Window
Day 1
6 to 8 Days 
After 
Visit 1
28 to 35 
Days After 
Visit 1
84 to 98 
Days After 
Visit 1
175 to 189 
Days After 
Visit 1
Optimally 
Within 3 Days 
After 
Potential 
COVID-19 
Illness Onset
28 to 35 Days 
After 
Potential 
COVID-19 
Illness Visit
Ask/remind the participant or participant’s 
parent(s)/legal guardian to contact site 
immediately if participant experiences any 
symptoms of acute chest pain, shortness of 
breath, or palpitations
X
X
X*
Refer to 
Section 8.10.11.
*From Cohort 4 onwards, 
symptoms reported through 
6 weeks after study 
intervention.
Review reactogenicity e-diary data (daily 
review is optimal during the active diary 
period)
If Visit 2 occurs on Day 6, 
continue to review e-diary 
data through Day 7.
Review ongoing reactogenicity e-diary 
symptoms and obtain stop dates
X
X
Collect AEs and SAEs as appropriate
X
X
X
X
X
X
X
Includes nonserious AEs 
through Visit 3, any AEs 
occurring up to 48 hours 
after a blood draw or nasal 
swab collection, and SAEs 
through the end of study 
(see Section 8.4.1).
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 40
Notes
Visit Identifier
1
2
3
4
5
Unplanned
Unplanned
Visit Description
Vax 1 
Visit
1-Week 
Follow-Up 
Visit
(Vax 1)
1-Month 
Follow-Up 
Visit
(Vax 1)
3-Month 
Follow-Up 
Visit
(Vax 1)
6-Month 
Follow-Up 
Visit
(Vax 1)
Potential 
COVID-19
Illness Visit
Potential 
COVID-19 
Convalescent 
Visit
The COVID-19 illness visit 
may be conducted as an 
in-person or telehealth 
visit.
The COVID-19 illness visit 
is only conducted for 
symptomatic participants. 
See Section 8.10.7.
Visit Window
Day 1
6 to 8 Days 
After 
Visit 1
28 to 35 
Days After 
Visit 1
84 to 98 
Days After 
Visit 1
175 to 189 
Days After 
Visit 1
Optimally 
Within 3 Days 
After 
Potential 
COVID-19 
Illness Onset
28 to 35 Days 
After 
Potential 
COVID-19 
Illness Visit
Collection of COVID-19/MIS-C–related 
clinical and laboratory information 
(including local diagnosis)
X
X
Assist the participant or participant’s 
parent(s)/legal guardian to delete the e-diary
application or collect the provisioned device
X
Abbreviations: CRF = case report form; HLA = human leukocyte antigen; IRT = interactive response technology; MIS-C = multisystem inflammatory syndrome in children; 
NAAT = nucleic acid amplification test; PBMC = peripheral blood mononuclear cell; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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2. INTRODUCTION
BNT162b2 (Comirnaty) is an RNA-based vaccine that, as of April 2022, was granted full 
marketing authorization, conditional marketing authorization, EUA, or temporary 
authorization in a total of more than 140 countries for the prevention of COVID-19 caused 
by SARS-CoV-2.1 In the US, it has been fully licensed for use in individuals 16 years of age 
and above as of 23 August 2021.2  A third dose of BNT162b2 has been granted EUA in the 
US and many other countries to reduce the risk of infection in light of emerging new 
SARS-CoV-2 variants and increasing incidence of COVID-19 disease.3,4,5  In the US, a 
fourth dose was granted EUA for individuals 50 years of age and older as well as for 
individuals 12 years of age and older with certain kinds of immunocompromising 
conditions.6  The bivalent vaccine BNT162b2 Bivalent (Original and Omicron BA.4/BA.5) 
was first authorized for emergency use in the US on 31 August 2022 for individuals 12 years 
of age and older as a single booster dose after either completion of primary vaccination or 
after the most recent booster dose with an authorized or approved monovalent COVID-19 
vaccine.7 Finally, as of 18 April 2023, US FDA reissued the EUA for the current bivalent 
mRNA COVID-19 vaccines to be used for all doses administered to individuals 6 months of 
age and older.8
All versions of the vaccine encode the spike protein(s) with a modRNA, encapsulated in 
RNA-LNPs, which has demonstrated potent immunogenicity, high VE, and a favorable 
safety profile in Phase 1, 2, and 3 human trials,9 as well as in real-world usage.10 As 
SARS-CoV-2 continues to circulate at very high levels,11 Pfizer/BioNTech are investigating 
next-generation, RNA-based COVID-19 vaccines, including BNT162b5, BNT162b6 and 
BNT162b7 bivalent and BNT162b7 monovalent vaccines, to further protect against 
COVID-19 caused by other emergent and potentially more antigenically diverse variants.
2.1. Study Rationale
Since the start of the pandemic, several variants have emerged, causing surges in infection 
rates, despite uptake of vaccines. Currently, the SARS-CoV-2 Omicron variant B.1.1.529 
remains dominant in many countries though the prevalence of its sublineages has rapidly 
changed in recent months.11,12 Within the US, in late May 2022,  the BA.2 and BA.2.12.1 
sublineages accounted for the majority of sequenced COVID-19 cases, by mid-August 2022, 
BA.4 and BA.5 accounted for the majority, and by the end of January 2023, the XBB 
sublineages accounted for the majority.13 The most current weighted estimates from the 
CDC for the 2-week period ending on 10 June 2023 for all sequenced cases reported for the 
Omicron sublineages in the US were as follows (those above 3%): XBB.1.5 (40%), 
XBB.1.16 (11.8%), XBB.1.9.1 (9.4%),, XBB.2.3 (8.5%), XBB.1.16.1 (6.2%), 
XBB.1.9.2 (5.9%), XBB (4.8%), and EG.5 (3.7%).14
The UK Health Security Agency reports that the effectiveness of ChAdOx1-S, BNT162b2, 
and mRNA-1273 (pooled analysis) against hospitalization is 88% (range, 78%-93%) for the 
Omicron variant 2 or more weeks after a booster dose.15  However, other studies have 
demonstrated that the effectiveness of BNT162b2 against SARS-CoV-2 infection and 
COVID-19 disease wanes over a period of months, particularly in the context of 
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Final Protocol Amendment 6, 27 Jul 2023
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 42
variants.16,17,18 In light of this waning effectiveness of the primary 2-dose series of 
BNT162b2 as well as the existence of variants with cumulative mutations in the spike protein 
that are resilient to the existing immune response, particularly the Omicron variant, 
development of new vaccine that could generate an improved immune response, including 
against other variants, could help better protect individuals against COVID-19.
Based on this rationale, Pfizer-BioNTech will evaluate the following vaccine candidates:
Original protocol (Cohort 1): BNT162b5 Bivalent (WT/OMI BA.2) consists of BNT162b5
Wild Type (ancestral strain, Wuhan-Hu-1; USA-WA1/2020) combined with BNT162b5
OMICRON (BA.2 sublineage), which has been designed to produce an improved antibody 
response against SARS-CoV-2. BNT162b5 Bivalent (WT/OMI BA.2) uses the same
modRNA platform, manufacturing processes, and LNP formulation as BNT162b2. Its active 
substance is a modified version of the mRNA segment used in BNT162b2 encoding the spike 
protein of SARS-CoV-2.
Protocol amendments 1 and 2 (Cohorts 2 and 3): Because of the emergence of other Omicron 
sublineages, such as Omicron BA.4 and BA.5, which alone account for 5.3% (BA.4) and 
88.8% (BA.5) of sequenced COVID-19 cases as of the week ending 13 August 2022,13 and in 
line with a request by the FDA to begin clinical trials with modified vaccines containing an 
Omicron BA.4/BA.5 component,19 a second cohort of approximately 500 participants has 
been added to the study in protocol amendment 1 to evaluate BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) given as a second booster dose in BNT162b2-experienced 
participants ≥12 years of age. Cohort 2 will also investigate a higher dose (60 µg) of 
BNT162b2 (WT/OMI BA.4/BA.5) in participants ≥18 years of age. A third cohort of 
approximately 400 participants has been added to the study in protocol amendment 2 in order 
to have sufficient power to evaluate BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg as a 
second booster dose in BNT162b2-experienced participants ≥18 years of age. BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) consists of the original SARS-CoV-2 spike protein mRNA, 
targeting the ancestral strain of the virus, in combination with mRNA encoding the spike 
protein of the Omicron variant (BA.4/BA.5 sublineage).
Multiple real-world studies show that the bivalent (Original/OMI BA.4/BA.5) mRNA 
COVID-19 vaccine provides effective protection against hospitalization and additional 
protection among persons previously vaccinated with only WT-based mRNA vaccine(s). 
Reported absolute vaccine effectiveness against hospitalization (reference group: 
unvaccinated) has ranged from 59% (95% CI: 44, 70) among immunocompetent adults 
≥18 years of age20 to 84% (95% CI: 64, 93) among immunocompetent adults ≥65 years of 
age.21 Reported relative vaccine effectiveness against severe illness (reference group: only 
≥2 WT-based mRNA doses) has ranged from approximately 40% to 80%, with estimates 
varying depending on factors such as age, time since last WT-based dose, and time elapsed 
since a prior SARS-CoV-2 infection.22,23,24 However, as the real-world evidence describing 
bivalent vaccine effectiveness continues to accumulate, several reports suggest that vaccine 
effectiveness against severe illness may potentially wane approximately 2 to 4 months after
bivalent vaccination,23,24,25 though additional data continue to accumulate to better 
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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Final Protocol Amendment 6, 27 Jul 2023
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TMF Doc ID: 164.01
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characterize duration of protection. In light of early evidence of waning effectiveness of the 
bivalent (Original/OMI BA.4/BA.5) mRNA COVID-19 vaccine during periods when the 
subsequent Omicron sublineages were in circulation (BQ.1/BQ.1.1 and XBB/XBB.1.5), 
development of a more efficacious and durable vaccine that could generate an improved, 
longer-lasting immune response, including against current and newly emergent variants and 
lineages, could help better protect individuals against COVID-19.
Protocol amendment 6 (Cohort 4): Based on the above rationale, Pfizer-BioNTech will now 
evaluate new BNT162b bivalent and/or monovalent vaccines (BNT162b5, BNT162b6, and 
BNT162b7) containing different prefusion-stabilized versions of the SARS-CoV-2 spike 
encoded from mRNA. These vaccines use the same modRNA platform, manufacturing 
processes, and LNP formulation as BNT162b2. The modifications of the mRNA segment(s)
are intended to expose a broader array of neutralizing epitopes in the spike protein(s), hence 
potentially improving the immunogenic response. The modifications for a specific vaccine 
design (BNT162b5, BNT162b6, BNT162b7) are consistent, irrespective of vaccine valency 
and strain background.  Specifically, the following vaccine candidates will be evaluated in 
Cohort 4: BNT162b5 Bivalent (Original/OMI BA.4/BA.5), BNT162b6 Bivalent 
(Original/OMI BA.4/BA.5), and BNT162b7 Bivalent (Original/OMI BA.4/BA.5). In 
addition, BNT162b7 Monovalent (OMI BA.4/BA.5) will be evaluated. BNT162b2 Bivalent 
(Original/OMI BA.4/BA.5) will be included as comparator.
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 protein–
specific antibodies.26,27 Therefore, vaccines targeting the spike protein of SARS-CoV-2 have 
been used as a critical mitigation strategy of the COVID-19 pandemic. However, waning 
effectiveness of the authorized vaccines has been shown to occur over time and is due to the 
emergence of variants.
A large study conducted in 10 states within the US noted waning mRNA vaccine 
effectiveness against emergency room and urgent care encounters as well as hospitalizations, 
when comparing 2 months versus >4 months after receipt of a third dose. During the 
Omicron period, VE against emergency room or urgent care visits was 87% during the first 
2 months after a third dose and decreased to 66% among those vaccinated 4 to 5 months 
earlier; VE against hospitalizations was 91% during the first 2 months following a third dose 
and decreased to 78% ≥4 months after a third dose.17 In another large study conducted in 
approximately 2.5 million UK adults vaccinated with either ChAdOx1, BNT162b2, or 
mRNA-1273, approximately 80% of the participants with SARS-CoV-2 had Omicron variant 
infections and approximately 20% had Delta variant infections.  In those who received 
3 doses of BNT162b2, VE increased to 67.2% at 2 to 4 weeks before declining to 45.7% at 
10 or more weeks.18
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A recent laboratory study in Israel compared the neutralization of Omicron-infected cells in 
serum samples obtained from participants who had received 2 doses of BNT162b2 with 
neutralization in samples obtained from participants who had received 3 doses of BNT162b2. 
The neutralization efficiency of BNT162b2 was also tested against wild-type SARS-CoV-2 
and the Beta, Delta, and Omicron variants. The importance of a third vaccine dose was 
evidenced by a higher neutralization efficiency (by a factor of 100) against the Omicron 
variant after the third dose compared to the second dose. However, even with 3 vaccine 
doses, neutralization against the Omicron variant was lower (by a factor of 4) than that 
against the Delta variant.28 Moreover, the Omicron sublineages BA.4 and BA.5 have 
demonstrated substantial immune escape from neutralizing antibodies induced by both 
infection and immunization,29 which has been attributed to the L452R and F486V spike 
mutations within the protein sequence of BA.4 and BA.5.30  SARS-CoV-2 has continued to 
evolve with the recombinant XBB sublineages dominating within the US and globally by the 
end of March 2023.12,13 The XBB sublineages that have become most prevalent have a 
hallmark F486P mutation that confers further immune escape and host receptor affinity.13,31,32
BNT162b5, BNT162b6, and BNT162b7 contain stabilized versions of the original 
SARS-CoV-2 spike protein mRNA that improve upon the BNT162b2 design in further 
constraining the spike in a prefusion conformation and the RBD in a state that may be more 
favorable to the presentation of broadly neutralizing epitopes. The designs of BNT162b5, 
BNT162b6, and BNT162b7 differ from that of BNT162b2 in the addition of proline 
substitutions to further stabilize the prefusion conformation. BNT162b6 and BNT162b7 
additionally differ from BNT162b5 at 2 of those proline substitutions as well as in the 
addition of cysteine residues to form an interprotomer disulfide bridge. BNT162b6 and 
BNT162b7 also differ from one another at the location of their cysteine mutations, resulting 
in differences in the location and distance of the disulfide bridges and consequent constraint 
of the RBD positioning. Nonclinical studies show that these designs increase prefusion spike 
thermostability and improve immunogenicity compared to BNT162b2 when administered as 
a booster dose or primary series in mice.
A recommendation issued by the FDA on 30 June 2022 described the need to modify 
existing vaccines to address circulating variants and requested manufacturers to begin
clinical trials with modified vaccines containing an Omicron BA.4/BA.5 component.19 The
additional studies to evaluate BNT162b vaccines, targeting emerging Omicron sublineages 
and other variants, may further inform decision-making for future vaccinations as the 
pandemic further evolves.
2.2.1. Clinical Overview
Study C4591001 (NCT04368728) is a Phase 1/2/3 trial in ~46,000 participants designed to 
generate safety, tolerability, immunogenicity, and efficacy data from a novel RNA-based 
vaccine candidate.33 The trial is being conducted in a heterogeneous study population: 
eligible participants ≥12 years of age, healthy participants, including those participants with 
stable chronic medical conditions, including HIV-, HCV-, and HBV-positive participants. 
The study consists of 2 parts: Phase 1: to identify the preferred vaccine candidate 
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(BNT162b1 or BNT162b2) and dose level (10 µg, 20 µg, 30 µg, or 100 µg [for BNT162b1]); 
Phase 2/3: an expanded-cohort and efficacy part to evaluate the selected vaccine candidate 
(BNT162b2).
The 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. 
BNT162b2 was selected from the Phase 1 part of the study based on the overall safety, 
tolerability, and immunogenicity. In a mid–November 2020 analysis of 36,621 participants 
randomized 1:1 to vaccine or placebo 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. Subgroup analyses of the primary efficacy endpoint showed similar efficacy point 
estimates across age groups, sexes, racial and ethnic groups, and participants with medical 
comorbidities associated with high risk of severe COVID-19. Secondary efficacy analyses 
suggested benefit of the vaccine in preventing severe COVID-19, in preventing COVID-19 
following the first dose, and in preventing COVID-19 in individuals with prior SARS-CoV-2 
infection, although available data for these outcomes did not allow for firm conclusions.34
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.35 Furthermore, from the same analysis, BNT162b2 was 
shown to have an efficacy of:

100% in preventing severe disease as defined by the CDC.

95.3% in preventing severe disease as defined by the FDA.

100% in preventing COVID-19 cases in South Africa, where the B.1.351 lineage is 
prevalent.
Safety data from approximately 38,000 participants at least 16 years of age randomized 1:1 
to vaccine or placebo with a median of 2 months of follow-up after the second dose 
demonstrated a favorable safety profile. Available safety data from all participants enrolled 
through the 14 November 2020 data cutoff (N = 43,252), which includes late enrollment of 
additional adolescent and adult participants, were consistent with the safety profile for the 
approximately 38,000 participants with a median follow-up of 2 months and also did not 
raise specific safety concerns.34
A booster dose (Dose 3) of BNT162b2 was administered to 306 Phase 3 participants without 
prior evidence of SARS-CoV-2 infection ~6 months after completing the 2-dose schedule. 
The immune response 1 month after administration of Dose 3 was noninferior to that 
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observed 1 month after Dose 2 in the same participants. Furthermore, from the same 
analysis, among participants without prior evidence of SARS-CoV-2 infection up to 1 month 
after Dose 3, a high proportion of participants (99.5%) had a seroresponse at 1 month after 
Dose 3 compared with 98.0% at 1 month after Dose 2.9
On 22 September 2021, based on safety and immunogenicity data from approximately 
300 immunocompetent adult booster dose recipients from Study C4591001, the FDA issued 
the EUA for a single booster dose of BNT162b2 30 µg for 1) individuals 65 years of age and 
older; 2) individuals 18 through 64 years of age at high risk of severe COVID-19; and 
3) individuals 18 through 64 years of age whose frequent institutional or occupational 
exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19, 
including severe COVID-19.36 On 19 November 2021, the FDA amended the EUA, 
authorizing use of a single booster dose for all individuals 18 years of age and older after 
completion of primary vaccination with an FDA-approved COVID-19 vaccine.37
On 09 December 2021, the FDA again amended the EUA to authorize the use of a single 
booster dose for administration to individuals 16 and 17 years of age at least 6 months after 
completion of primary vaccination with BNT162b2.3 In addition, a booster dose of the 
vaccine is authorized in the EU and other countries, with recommendations for populations 
varying based on local health authority guidance.4,5
The per-protocol interim safety and efficacy analysis was conducted in October 2021 for 
Study C4591031 Substudy A.  In this study, approximately 10,000 participants who had 
previously received 2 doses of BNT162b2 as a primary series in Study C4591001 were 
randomized 1:1 in Study C4591031 to receive either a 30-µg booster dose (the same dosage 
strength as in the 2-dose primary series) or placebo.  The time between the second dose and 
administration of the booster dose or placebo for most participants was ≥10 to <12 months.
Symptomatic COVID-19 occurrence was measured from ≥7 days after booster or placebo, 
with a median follow-up of 2.5 months.  During the blinded placebo-controlled study period 
up to a data cutoff date of 05 October 2021, there were a total of 6 cases of COVID-19 in the 
booster group and 123 cases in the nonboosted placebo group, in the evaluable efficacy 
population without evidence of prior SARS-CoV-2 infection.  The observed relative VE was 
95.3% (2-sided 95% CI: 89.5%, 98.3%), which reflects the reduction in disease occurrence in 
the boosted group versus the nonboosted group.  The AE profile was generally consistent 
with other previously submitted clinical safety data for the vaccine, with no new safety 
concerns identified.  No cases of myocarditis or pericarditis were reported.38
C4591031 Substudy E is an ongoing Phase 3 trial in approximately 2900 participants 
18 years of age and older who have previously received 3 doses of BNT162b2 (30-µg dose). 
Participants in this substudy received a fourth dose of either BNT162b2 or BNT162b2 
OMICRON (BA.1 sublineage) or a combination of both at a total dose level of either 30 µg 
or 60 µg. From the available safety data from this study, in participants 18 through 55 years 
of age, the monovalent Omicron-modified vaccine (at a 30-μg dose level) showed a similar 
local and systemic reactogenicity event profile as the prototype BNT162b2 vaccine at the 
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same dose level. In participants >55 years of age, monovalent and bivalent 
Omicron-modified vaccines at the 30-μg dose level showed a similar local and systemic 
reactogenicity event profile as the prototype BNT162b2 vaccine. In the older age group at 
the 60-μg dose level, mild to moderate injection site pain, fatigue, and muscle pain were 
more common compared to the 30-µg dose level. In participants >55 years of age, without 
evidence of COVID-19 infection, Omicron BA.1 neutralization activity substantially 
increased with an Omicron-modified monovalent or bivalent vaccine as a fourth dose. 
Moreover, the Omicron-modified variant vaccines as a fourth dose elicit improved Omicron 
response against the Omicron BA.4/BA.5 sublineages, albeit at a lower level compared to the 
response against Omicron BA.1.39
Original protocol, protocol amendments 1 and 2:  BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) and BNT162b5 Bivalent (WT/OMI BA.2) have not been administered to 
humans before; however, they are highly similar to the combination vaccine under evaluation
in C4591031 Substudy E.
Protocol amendment 6:  Since the prevalence of Omicron sublineages remains high following 
the EUA of BNT162b2 Bivalent (Original/OMI BA.4/BA.5), this study will now evaluate
additional new bivalent vaccines targeting the ancestral strain and Omicron BA.4/BA.5 and a 
new monovalent vaccine targeting Omicron BA.4/BA.5 alone.
2.3. Benefit/Risk Assessment
There is an ongoing global pandemic of COVID-19 with several SARS-CoV-2 vaccines now 
in use under marketing authorizations or EUAs. The available safety and immunogenicity 
data from ongoing Pfizer-BioNTech clinical trials and real-world effectiveness and safety 
data, combined with available nonclinical data with BNT162 vaccines and data from 
nonclinical and clinical trials with the same or related RNA components or antigens, support 
a favorable benefit/risk profile and support continued clinical development of BNT162b2, 
BNT162b5, BNT162b6, and BNT162b7 bivalent and monovalent vaccines.
Continued clinical investigation is justified, given:

The threat posed by the increasing number of globally distributed outbreaks of 
SARS-CoV-2 infection.

The threat posed by the SARS-CoV-2 variants emerging worldwide.

The potential need for enhancing immune responses to overcome waning immunity.

The likelihood that COVID-19 will become endemic and a seasonal burden like other 
respiratory pathogens.40,41
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of the study interventions may be found in the IB, which is the SRSD for this 
study.
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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Interventions: BNT162b2 Bivalent, BNT162b5 Bivalent, BNT162b6 Bivalent, BNT162b7 Bivalent, and BNT162b7 Monovalent RNA-Based 
COVID-19 Vaccine Candidates 
For BNT162b2:
Pfizer has identified the most common risks for 
BNT162b2 as local reactions, such as injection site 
redness, injection site swelling, and injection site 
pain, and systemic events, such as fever, fatigue, 
headache, chills, muscle pain, and joint pain.
Other risks identified by Pfizer for BNT162b2 are 
lymphadenopathy; hypersensitivity reactions, such 
as rash, pruritus, urticaria, angioedema, and 
anaphylaxis; and myocarditis and pericarditis.
The identified adverse reactions in local product 
labels may vary depending on the requirements of 
the respective regulatory authorities (eg, EU-SmPC 
and USPI). 
For BNT162b2 Omicron-modified vaccines, 
BNT162b2 OMICRON (BA.1 sublineage) and 
BNT162b2 OMICRON (BA.4/BA.5 sublineage):
These vaccines have the same modRNA platform 
(with sequence changes limited to those that are 
Omicron-specific) and LNP formulation as 
BNT162b2; and the safety profile has been similar 
to that of BNT162b2.
For BNT162b5 and BNT162b6 bivalent and 
BNT162b7 monovalent and bivalent vaccines:
These vaccines have the same modRNA platform 
(with sequence changes intended to improve the 
These are common adverse reactions seen with 
other vaccines as well as the COVID-19 vaccine.
Data available from the C4591001 study 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.34
Data available from the C4591031 Substudy E 
showed that mild to moderate injection site pain, 
fatigue, and muscle pain were more common 
following a 60-µg dose compared to a 30-µg 
dose.
Anaphylaxis: Frequency not known.
Myocarditis and pericarditis: Very rare cases of 
myocarditis and pericarditis have been reported 
following vaccination with mRNA COVID-19 
vaccines. Typically, the cases have occurred 
more often in younger men and after the second 
dose of the vaccine and within 14 days after 
vaccination. Based on accumulating data, the 
reporting rates of myocarditis and pericarditis 
after primary series in children ages 5 to 
<12 years are lower than in ages 12 through 
17 years. Rates of myocarditis and pericarditis 
after additional doses do not appear to be higher 
Local reactions and systemic events will be 
recorded using a reactogenicity e-diary to monitor 
local reactions and systemic events in real time.
Collection of AEs from signing of the ICD 
through 1 month and SAEs through 6 months after 
study vaccination.
DMC review throughout the study to review all 
safety data.
Specific reference to identified 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 8.10.11.
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
immune response [BNT162b5, BNT162b6, 
BNT162b7] and that are Omicron-specific
[BNT162b5 OMICRON (BA.2 sublineage),
BNT162b5 OMICRON (BA.4/BA.5 sublineage), 
BNT162b6 OMICRON (BA.4/BA.5 sublineage), 
and BNT162b7 OMICRON (BA.4/BA.5 
sublineage)]) and LNP formulations as BNT162b2; 
and the safety profile has not been found to be 
different from that of BNT162b2.
than after the second dose. These cases are 
generally mild, 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 previous 
studies and has resulted in identification of some 
additional adverse reactions (risks) as noted in 
the SRSD.
Study Procedures
Original protocol and amendments 1 and 2: 
Participants will be required to attend healthcare 
facilities during the global SARS-CoV-2 pandemic.
Without appropriate social distancing and PPE, 
there is a potential for increased exposure to 
SARS-CoV-2.
Pfizer will work with sites to ensure an appropriate 
COVID-19 prevention strategy.
Monitoring for cases of COVID-19 developing 
during the study as part of the COVID-19 
surveillance.
Venipuncture will be performed during the study.
There is the risk of bleeding, bruising, 
hematoma formation, and infection at the 
venipuncture site.
Only appropriately qualified personnel will obtain 
the blood draw.
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2.3.2. Benefit Assessment
Benefits to individual participants enrolled in the study may be:

Receipt of a further dose of an efficacious or potentially efficacious COVID-19 vaccine 
that may convey better protection against the SARS-CoV-2 wild-type (ancestral) strain
and/or variants [original protocol and amendments 1 and 2: during a global pandemic].

Contributing to research to help others [original protocol and amendments 1 and 2: in a 
time of global pandemic].
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures to minimize risk to study participants as stated in 
Section 2.3.1, the potential risks identified in association with BNT162b RNA-based 
COVID-19 vaccines are justified by the anticipated benefits that may be afforded to healthy 
participants.
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS
Refer to Table 1, Table 3, and Table 4 for details of the Cohort 2 group, Cohort 3 group, and 
Cohort 4 group, respectively.
Objectives
Estimands
Endpoints
Primary Safety
Cohort 1: To describe the safety 
and tolerability profile of 
BNT162b5 Bivalent
(WT/OMI BA.2) 30 µg and 
BNT162b2 Bivalent 
(WT/OMI BA.1) 30 µg given as a
second booster dose to COVID-19
vaccine–experienced participants 
18 through 55 years of age.
In participants receiving 1 dose of study 
intervention, the percentage of participants 
reporting:

Local reactions for up to 7 days 
following the study vaccination

Systemic events for up to 7 days 
following the study vaccination

AEs from the study vaccination through 
1 month after the study vaccination

SAEs from the study vaccination 
through 6 months after the study 
vaccination

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
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Objectives
Estimands
Endpoints
Cohort 2: To describe the safety 
and tolerability profile of 
BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) 30 µg given as a 
second booster dose to 
BNT162b2-experienced 
participants 12 through 17, 
18 through 55, and 55 years of 
age, and BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 60 µg
given as a second booster dose to 
BNT162b2-experienced 
participants 18 through 55 and 
>55 years of age.
In participants receiving 1 dose of study 
intervention, the percentage of participants 
reporting:

Local reactions for up to 7 days 
following the study vaccination

Systemic events for up to 7 days 
following the study vaccination

AEs from the study vaccination through 
1 month after the study vaccination

SAEs from the study vaccination 
through 6 months after the study 
vaccination

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
Cohort 2 + Cohort 3 combined: 
To describe the safety and 
tolerability profile of BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 
30 µg given as a second booster 
dose to BNT162b2-experienced 
participants 18 through 55 and 
55 years of age.
In participants receiving 1 dose of study 
intervention, the percentage of participants 
reporting:

Local reactions for up to 7 days 
following the study vaccination

Systemic events for up to 7 days 
following the study vaccination

AEs from the study vaccination through 
1 month after the study vaccination

SAEs from the study vaccination 
through 6 months after the study 
vaccination

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
Cohort 4a: To describe the safety 
and tolerability profile of 
BNT162b2 Bivalent 30 µg, 
BNT162b5 Bivalent 30 µg, 
BNT162b6 Bivalent 30 µg, 
BNT162b7 Bivalent 30 µg, and 
BNT162b7 Monovalent 30 µg 
given to mRNA COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants receiving 1 dose of study 
intervention, the percentage of participants 
reporting:

Local reactions for up to 7 days 
following the study vaccination

Systemic events for up to 7 days 
following the study vaccination

AEs from the study vaccination through 
1 month after the study vaccination

SAEs from the study vaccination 
through 6 months after the study 
vaccination

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
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Objectives
Estimands
Endpoints
Primary Immunogenicity
Cohort 1: To describe the immune 
response to BNT162b5 Bivalent 
(WT/OMI BA.2) 30 µg and 
BNT162b2 Bivalent 
(WT/OMI BA.1) 30 µg given as a 
second booster dose to COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMT at baseline and 1 month after the 
study vaccination for each strain-
specific neutralizing titer

GMFR from before the study 
vaccination to 1 month after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 1 month after the 
study vaccination for each strain-
specific neutralizing titer

SARS-CoV-2 
Omicron (BA.2)–
neutralizing titers

SARS-CoV-2 
Omicron (BA.1)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 2/Group 4 + Cohort 3/ 
Group 2 combined: To 
demonstrate the superiority with 
respect to level of neutralizing titer 
and noninferiority with respect to 
seroresponse rate of the 
anti-Omicron BA.4/BA.5 immune 
response after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg
compared to after BNT162b2 
30 µgd given as a second booster 
dose to BNT162b2-experienced 
participants >55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMR of the Omicron (BA.4/BA.5)–
neutralizing titers 1 month after 
BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) to 1 month after 
BNT162b2, given as a second booster 
dose in BNT162b2-experienced 
participants

The difference in percentages of 
participants with seroresponse to the 
Omicron BA.4/BA.5 strain at 1 month 
after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) and at 1 month 
after BNT162b2 given as a second 
booster dose in 
BNT162b2-experienced participants

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers
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Objectives
Estimands
Endpoints
Cohort 2/Group 2 + 
Cohort 3/Group 1 combined and 
Cohort 2/Group 4 + Cohort 
3/Group 2 combined: To 
demonstrate the noninferiority 
with respect to level of 
neutralizing titer and with respect 
to seroresponse rate of the 
anti-Omicron BA.4/BA.5 immune 
response after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg
given as a second booster dose to 
BNT162b2-experienced 
participants 18 through 55 years of 
age compared to participants 
>55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMR of the Omicron (BA.4/BA.5)–
neutralizing titers at 1 month after 
BNT162b2 Bivalent (WT/OMI
BA.4/BA.5) given as a second booster 
dose in BNT162b2-experienced 
participants 18 through 55 years of age 
compared to participants >55 years of 
age

The difference in percentages of 
participants with seroresponse to the 
Omicron BA.4/BA.5 strain at 1 month 
after BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) given as a second booster 
dose in BNT162b2-experienced 
participants 18 through 55 years of age 
compared to participants >55 years of 
age

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers
Cohort 2: To describe the immune 
response to BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg or 
60 µg and BNT162b2 Bivalent 
(WT/OMI BA.1) 30 µge or 60 µge
given as a second booster dose to 
BNT162b2-experienced 
participants 12 through 17, 18 
through 55,e and 55e years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMT at baseline and 1 month after the
study vaccination for each strain-
specific neutralizing titer

GMFR from before the study 
vaccination to 1 month after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 1 month after study
vaccination for each strain-specific 
neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
Omicron (BA.1)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 4a: To describe the immune 
response to BNT162b2 Bivalent 
30 µg, BNT162b5 Bivalent 30 µg,
BNT162b6 Bivalent 30 µg, 
BNT162b7 Bivalent 30 µg, and
BNT162b7 Monovalent 30 µg 
given to mRNA COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants): 

GMT at baseline and 1 month after the 
study vaccination for each strain-
specific neutralizing titer

GMFR from before the study 
vaccination to 1 month after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
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Objectives
Estimands
Endpoints
Secondary Immunogenicity
Cohort 2/Group 4 + 
Cohort 3/Group 2 combined: To 
demonstrate the noninferiority of 
the anti–reference-strain immune 
response after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg
compared to BNT162b2 30 µgd
given as a second booster dose in 
BNT162b2-experienced 
participants >55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMR of the reference-strain–
neutralizing titers at 1 month after 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) and at 1 month 
after BNT162b2 given as a second 
booster dose in 
BNT162b2-experienced participants

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 2/Group 2 + Cohort 
3/Group 1 combinedf and Cohort 
2/Group 4 + Cohort 3/Group 2 
combined: To describe the 
immune response to BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 
30 µg compared to BNT162b2 
30 µgd given as a second booster 
dose to BNT162b2-experienced 
participants 18 through 55 and 
>55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):

GMT at baseline and 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to 1 month after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 1 month after the 
study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Exploratory
Cohort 1: To describe the immune 
response to BNT162b5 Bivalent 
(WT/OMI BA.2) 30 µg and 
BNT162b2 Bivalent 
(WT/OMI BA.1) 30 µg given as a 
second booster dose to COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants): 
At baseline and 7 days, 1 month, 3 months,
and 6 months after study vaccination,

GMT at each time point for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to 7 days after the study 
vaccination for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at 7 days after the study 
vaccination for each strain-specific 
neutralizing titer

SARS-CoV-2 
Omicron (BA.2)–
neutralizing titers

SARS-CoV-2 
Omicron (BA.1)–
neutralizing titers

SARS-CoV-2 
reference-strainc –
neutralizing titers
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Objectives
Estimands
Endpoints
Cohort 2/Group 1, Cohort 2/Group 
2 + Cohort 3/Group 1 combined,f  
Cohort 2/Group 4 + 
Cohort 3/Group 2 combined,f
Cohort 2/Group 3, and Cohort 
2/Group 5: To describe the 
immune response to BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 
30 µg or 60 µg compared to 
BNT162b2 30 µgf given as a 
second booster dose to 
BNT162b2-experienced 
participants 12 through 17, 
18 through 55, and >55 years of 
age.
In participants complying with the key 
protocol criteria (evaluable participants):
At baseline and 1 month, 3 months, and 
6 months after study vaccination,

GMT at each time point for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to each subsequent time 
point for each strain-specific 
neutralizing titer

Percentages of participants with 
seroresponseb at each time point 
following vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 4a: To describe the immune 
response to BNT162b2 Bivalent 
30 µg, BNT162b5 Bivalent 30 µg,
BNT162b6 Bivalent 30 µg,
BNT162b7 Bivalent 30 µg, and 
BNT162b7 Monovalent 30 µg 
given to mRNA COVID-19 
vaccine–experienced participants 
18 through 55 years of age.
In participants complying with the key 
protocol criteria (evaluable participants):
At baseline and 7 days, 1 month, 3 months,
and 6 months after study vaccination,

GMT at each time point for each 
strain-specific neutralizing titer

GMFR from before the study 
vaccination to each time point after the 
study vaccination for each 
strain-specific neutralizing titer

Percentages of participants with 
seroresponseb at each time point after 
the study vaccination for each 
strain-specific neutralizing titer

SARS-CoV-2 
Omicron 
(BA.4/BA.5)–
neutralizing titers

SARS-CoV-2 
reference-strainc–
neutralizing titers
Cohort 1, Cohort 2 + Cohort 3 
combined, and Cohort 4: To 
describe confirmed COVID-19 
and severe COVID-19 cases in 
each vaccine and age group.

Confirmed 
COVID-19 cases

Confirmed severe 
COVID-19 cases

Strain sequencing of 
COVID-19 cases
Cohort 1, Cohort 2 + Cohort 3 
combined, and Cohort 4: To 
describe the immune response to 
SARS-CoV-2 infection at the time 
of the COVID-19 illness visitg and 
at the convalescent visit.

SARS-CoV-2–
neutralizing titers 
previously specified 
for the respective 
cohorts
Cohort 1, Cohort 2 + Cohort 3 
combined, and Cohort 4: To 
describe the immune response to 
other emerging variants (under 
monitoring, of interest, and/or of 
concern).

SARS-CoV-2–
neutralizing titers for 
other variants (under 
monitoring, of
interest, and/or of 
concern) not already 
specified
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Objectives
Estimands
Endpoints
Cohort 2: To describe the 
cell-mediated immune response, 
and additional humoral immune 
response parameters, to the 
reference strainc and Omicron in a 
subset of participants with PBMC 
samples collected.
a.
The Cohort 4 bivalent vaccines target the SARS-CoV-2 Original strain and the Omicron variant
(BA.4/BA.5 sublineage).  The Cohort 4 monovalent vaccine targets the Omicron variant (BA.4/BA.5 
sublineage).
b.
Seroresponse is defined as achieving a ≥4-fold rise from the baseline (before the study vaccination). If 
the baseline measurement is below the LLOQ, the postvaccination measure of ≥4 × LLOQ is considered 
seroresponse.  
c.
Reference strain is also referred to as the Original, Wild Type, or ancestral strain (Wuhan-Hu-1; 
USA-WA1/2020).
d.
The participants >55 years of age from C4591031 Substudy E expanded cohort who received BNT162b2 
30 µg as a second booster dose will be used as comparator group for this objective.
e.
A subset of approximately 100 participants in each age group (18 through 55 years of age, >55 years of 
age) and dose group (30 µg, 60 µg) from C4591031 Substudy E expanded cohort who received 
BNT162b2 Bivalent (WT/OMI BA.1) 30 µg or 60 µg as a second booster dose will be selected for this 
objective. The subset selected from C4591031 Substudy E will include similar percentage of 
participants with baseline positive SARS-CoV-2 infection status as the groups in Cohort 2 of this study 
whenever feasible. 
f.
A subset of approximately 100 participants in each age group (18 through 55 years of age, >55 years of 
age) from C4591044 Cohort 2/Group 2 + Cohort 3/Group 1 combined and Cohort 2/Group 4 + 
Cohort 3/Group 2 combined who received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg and from 
the C4591031 Substudy E expanded cohort who received BNT162b2 30 µg as a second booster dose 
will be selected for this objective. The subset selected will include a similar percentage of participants 
with baseline positive SARS-CoV-2 infection status whenever feasible. 
g.
If the COVID-19 illness visit is conducted as an in-person visit, a blood sample will be taken for this 
assessment. No blood samples will be obtained for remote (telehealth) COVID-19 illness visits.
4. STUDY DESIGN
4.1. Overall Design
This study is a randomized, active-controlled study to evaluate the safety, tolerability, and 
immunogenicity of new bivalent and monovalent vaccines. The study duration for each 
participant will be approximately 6 months.  The study vaccine candidates are divided into 
cohorts, which may be studied in a staggered or parallel manner, as required by the clinical 
plan.
Refer to the schema in Section 1.2.
Based on review of safety or immunogenicity data of any study intervention group, at 
Pfizer’s discretion, subsequent collection of blood samples from participants in that group 
may be halted and/or not analyzed and study visits or other procedures may be discontinued.
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An EDMC will review cumulative unblinded data throughout the study. Refer to 
Appendix 1, Section 10.1.5.1.
Cohort 1 Design
For the purposes of this protocol, study intervention within this cohort refers to:

BNT162b5 Bivalent (WT/OMI BA.2) 30 µg

BNT162b2 Bivalent (WT/OMI BA.1) 30 µg
Participants 18 through 55 years of age will be randomized at a ratio of 1:1 to receive a single 
30-µg dose of 1 of the 2 study interventions as a second booster dose. Participants will be 
stratified by the number of months since the last dose of COVID-19 vaccine received prior to 
randomization (3 to 6 months [90 to 180 days] or >6 months [>180 days]).  Approximately 
200 participants will be enrolled in this cohort.
Cohort 2 Design
For the purposes of this protocol, study intervention within this cohort refers to: 

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 µg
Participants 12 through 17 years of age who have received 3 prior doses of BNT162b2 
(30-µg doses), with the most recent dose being 150 to 365 days prior to Visit 1 (Day 1), will 
receive a single 30-µg dose of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) as a second 
booster dose (open-label). Participants 18 through 55 and 55 years of age who have 
received 3 prior doses of BNT162b2 (30-µg doses), with the most recent dose being 150 to 
365 days prior to Visit 1 (Day 1), will be randomized 1:1 within each age group to receive 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at either 30 µg or 60 µg as a second booster dose 
(observer-blind). Approximately 500 participants will be enrolled into this cohort per 
Table 1.
Table 1.
Cohort 2 Design
Cohort 2: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
Group
Participant Age 
Group
Prior Doses of 
BNT162b2
Time Since 
Last Dose
Study 
Dose
Number of 
Participants
Randomization / 
Blind
1
12-17 years
3
150-365 days
30 µg
100
Open-label
2
18-55 years
3
150-365 days
30 µg
100
Randomized 1:1
Observer-blind
3
18-55 years
3
150-365 days
60 µg
100
4
55 years
3
150-365 days
30 µg
100
Randomized 1:1
Observer-blind
5
55 years
3
150-365 days
60 µg
100
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To evaluate the immunogenicity objective for Cohort 2, a subset of approximately 
100 participants in each age group (18 through 55 years of age, >55 years of age) and dose 
group (30 µg, 60 µg) from the C4591031 Substudy E expanded cohort who received Bivalent 
BNT162b2 (WT/OMI BA.1) 30 µg or 60 µg as a second booster dose will be selected as the 
control group for the descriptive immunogenicity summary (Table 2). The subset selected 
from C4591031 Substudy E will include similar percentage of participants with baseline 
positive SARS-CoV-2 infection status as the groups in Cohort 2 of this study whenever 
feasible.
Table 2.
Cohort 2 Immunogenicity Control Groups From C4591031 Substudy E
C4591031 Substudy E Subset
Participant Age Group
Vaccine Group
Dose
Number of Participants
18-55 years
Bivalent BNT162b2 (WT/OMI BA.1)
30 µg
100
18-55 years
Bivalent BNT162b2 (WT/OMI BA.1)
60 µg
100
55 years
Bivalent BNT162b2 (WT/OMI BA.1)
30 µg
100
55 years
Bivalent BNT162b2 (WT/OMI BA.1)
60 µg
100
Note: Vaccine group name in C4591031 Substudy E is “Bivalent BNT162b2 and BNT162b2 OMI.” 
Cohort 3 Design
For the purposes of this protocol, study intervention within this cohort refers to:

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg
Participants 18 years of age and older who have received 3 prior 30-µg doses of BNT162b2, 
with the most recent dose being 150 to 365 days prior to Visit 1 (Day 1), will receive a single 
30-µg dose of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) as a second booster dose 
(open-label).  Approximately 400 participants will be enrolled into this cohort per Table 3.
Table 3.
Cohort 3 Design
Cohort 3: BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
Group
Participant Age 
Group
Prior Doses of 
BNT162b2
Time Since 
Last Dose
Study 
Dose
Number of 
Participants
Randomization / 
Blind
1
18-55 years
3
150-365 days
30 µg
200
Open-label
2
55 years
3
150-365 days
30 µg
200
Open-label
Note: For certain safety and immunogenicity objectives, the 18- through 55-year age group 
and the >55-year age group will comprise participants from Cohorts 2 and 3 combined.
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Combining Cohort 2 and Cohort 3, there will be approximately 300 participants in each age 
group who received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg. To evaluate the 
primary immunogenicity hypothesis for the >55-year age group of Cohort 2 and Cohort 3 
combined, the participants >55 years of age from the C4591031 Substudy E expanded cohort 
who received BNT162b2 30 µg as a second booster dose will be used as comparator group
(approximately 300 participants [Expanded Enrollment – Group 1]).
Cohort 4: Participants 18 through 55 years of age who have received 3 or 4 prior doses of a 
US-authorized mRNA COVID-19 vaccine, with the most recent dose being a bivalent 
vaccine at least 150 days prior to Visit 1 (Day 1), will be enrolled. The Cohort 4 bivalent 
vaccines target the SARS-CoV-2 Original strain and the Omicron variant (BA.4/BA.5 
sublineage).  The Cohort 4 monovalent vaccine targets the Omicron variant (BA.4/BA.5 
sublineage). Participants will be randomized at a ratio of 1:1:1:1:1 to receive a single 30-µg 
dose of either BNT162b2 Bivalent, BNT162b5 Bivalent, BNT162b6 Bivalent, BNT162b7 
Bivalent, or BNT162b7 Monovalent (observer-blind).  Participants will be stratified by the 
number of prior doses (3 or 4 prior doses) of a US-authorized mRNA COVID-19 vaccine 
received prior to randomization.
Table 4.
Cohort 4 Design
Cohort 4: BNT162b Omicron BA.4/BA.5 Vaccine Candidates
All Participants 18 Through 55 Years of Age
Group
Study Intervention
Study 
Dose
Prior Doses 
of mRNA 
COVID-19 
Vaccine 
Time 
Since Last 
Dose
Number of 
Participants
Randomization / 
Blind
1
BNT162b2 Bivalent 
(Original/OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
Randomized
1:1:1:1:1
Observer-blind
2
BNT162b5 Bivalent 
(Original/OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
3
BNT162b6 Bivalent 
(Original/OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
4
BNT162b7 Bivalent 
(Original/OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
5
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
30 µg
3 or 4
≥150 days
60
4.2. Scientific Rationale for Study Design
The immune response following vaccination with BNT162b2 has been observed to wane 
with time, and a booster dose of BNT162b2 has demonstrated improvement in immune 
response, albeit to a lesser degree against some variants, particularly Omicron, of the original 
SARS-CoV-2 virus. The aim of the study is to improve the current protection elicited by 
BNT162b2.
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This is the first clinical study of BNT162b5 bivalent (Original/OMI BA.4/5), 
BNT162b6 bivalent (Original/OMI BA.4/5), and BNT162b7 monovalent and 
bivalent Omicron-modified vaccines. It was the first clinical study of BNT162b2 Bivalent 
(Original/OMI BA.4/BA.5) to evaluate the immune response to this new variant-targeted 
vaccine. Since the prevalence of Omicron sublineages remains high13 following the EUA of 
BNT162b2 Bivalent (Original/OMI BA.4/BA.5), this study will now evaluate additional new
bivalent vaccines targeting the ancestral strain and Omicron BA.4/BA.5
(BNT162b5 Bivalent, BNT162b6 Bivalent, and BNT162b7 Bivalent) and a new monovalent 
vaccine targeting Omicron BA.4/BA.5 alone (BNT162b7 Monovalent). The study design 
takes into account the similarity between the vaccines used in this study and the bivalent and 
monovalent vaccines currently being studied in C4591031 Substudy E (BNT162b2 Bivalent 
[WT/OMI BA.1] and BNT162b2 [OMI BA.1]) and that there have been no safety concerns 
to date with those vaccines. Likewise, the postauthorization use of BNT162b2 Bivalent 
(Original/OMI BA.4/BA.5) has not revealed any safety concerns to date. Prospective capture 
of confirmed COVID-19 cases with active COVID-19 surveillance and convalescent visits 
has been included.
4.2.1. Diversity of Study Population
Reasonable attempts will be made to enroll participants who align with the US population 
distribution (Census-based), in the age group of the study, to ensure that the study population 
is representative of patient populations that will benefit from a COVID-19 vaccine in clinical 
practice.
Given the relatively small size of the study, there may be less representation with respect to 
race, ethnicity, and geographic location.
4.2.2. Choice of Contraception/Barrier Requirements
BNT162b2 is approved for use without any contraceptive precautions. All investigational 
vaccines included in this study are RNA-LNP vaccines utilizing modRNA.  While there is no 
suspicion of human teratogenicity based on the intended pharmacology, some of the variant 
vaccine components under evaluation have not been administered to humans before and, 
therefore, contraception requirements have been included in this protocol. See Appendix 4
for contraception requirements.
4.3. Justification for Dose
Based on data from the Phase 1 component of clinical trial C4591001 and available 
nonclinical data, the modRNA BNT162b2 vaccine candidate was selected at a dose of 30 μg 
for Phase 2/3 evaluation of safety, immunogenicity, and efficacy after 2 doses administered 
3 weeks apart and is the authorized dose level for the third dose administered at least 
5 months following the second dose. The 30-μg dose level of BNT162b2 was shown to be 
effective and has been approved in multiple countries worldwide for the primary 2-dose 
series as well as for third and fourth doses. BNT162b2 Bivalent (Original/OMI BA.4/BA.5) 
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was granted EUA as a booster in the US at a 30-μg dose since 31 August 20227 and to be 
used for all doses, since 18 April 2023.8
Cohort 2 will also investigate a higher dose (60 µg) of BNT162b2 (WT/OMI BA.4/BA.5) in 
participants ≥18 years of age. Clinical trial C4591031 Substudy E is an ongoing study 
including participants 18 years of age and older who have previously received 3 doses of 
BNT162b2 (30-µg dose). A subset of participants in this substudy received BNT162b2 
Bivalent (WT/OMI BA.1) at a total dose level of either 30 µg or 60 µg as a second booster 
dose. From the available safety data from the study, the reactogenicity profile of the variant 
vaccines was overall similar to the prototype BNT162b2 vaccine. In participants >55 years 
of age, who received monovalent and bivalent Omicron-modified vaccines at the 60-µg dose 
level, mild to moderate injection site pain, fatigue, and muscle pain were more common 
compared to the 30-µg dose level.39 A subset of participants from C4591031 Substudy E 
(≥18 years of age) who received BNT162b2 (WT/OMI BA.1) 30 µg or 60 µg as a second 
booster dose will be randomly selected to achieve the primary immunogenicity objective of 
Cohort 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.
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.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Ages for each cohort as follows:
Cohort 1: Participants 18 through 55 years of age at randomization.
Cohort 2: Participants ≥12 years of age at Visit 1.
Cohort 3: Participants ≥18 years of age at Visit 1.
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Cohort 4: Participants 18 through 55 years of age at Visit 1.

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Participant and Disease Characteristics:
2. Participants and participants’ parent(s)/legal guardian(s), as appropriate, willing and able 
to comply with all scheduled visits/contacts, investigational plan, laboratory tests, and 
other study procedures.
3. Healthy participants who are determined by medical history, physical examination
(if indicated), 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. 
Informed Consent:
4. Capable of giving signed informed consent/assent as described in Appendix 1,
Section 10.1.3, which includes compliance with the requirements and restrictions listed in 
the ICD and in this protocol.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each study participant’s legal guardian (as defined in Appendix 1, 
Section 10.1.3) and the participant’s assent, when applicable, before any study-specific 
activity is performed. All legal guardians should be fully informed, and participants 
should be informed to the fullest extent possible, about the study in language and terms 
they are able to understand. The investigator will retain the original copy of each 
participant's signed consent/assent document.
Other Inclusion Criteria:
5. Cohort 1: Participants who have received 1 booster dose of a US-authorized COVID-19 
vaccine, with the last prior dose being 90 or more days before Visit 1 (Day 1).
Note: Documented confirmation of prior COVID-19 vaccines received must be obtained 
prior to randomization.  All prior COVID-19 vaccines must be authorized for use in the 
US.
Cohort 2 and Cohort 3: Participants who have received 3 prior doses of 30 µg 
BNT162b2, with the last dose being 150 to 365 days before Visit 1 (Day 1).
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Note: Documented confirmation of prior doses of BNT162b2 received must be obtained 
prior to randomization.
Cohort 4: Participants who have received 3 or 4 prior doses of a US-authorized mRNA 
COVID-19 vaccine (and dose level), with the last dose being a US-authorized Omicron 
BA.4/BA.5–adapted bivalent vaccine and dose level at least 150 days before Visit 1 
(Day 1).
Note: Documented confirmation of prior mRNA COVID-19 vaccines received must be 
obtained before randomization. Participants must have received mRNA COVID-19 
vaccines only.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study intervention(s).
2. Immunocompromised individuals with known or suspected immunodeficiency, as 
determined by history and/or laboratory/physical examination.
3. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
4. Women who are pregnant or breastfeeding.
5. Other medical or psychiatric condition, including recent (within the past year) or active 
suicidal ideation/behavior, or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the 
study.
Prior/Concomitant Therapy:
6. Receipt of chronic systemic treatment with known immunosuppressant medications 
(including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune 
disease), or radiotherapy, within 60 days before enrollment or planned receipt through 
conclusion of the study.
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Note: Chronic systemic corticosteroids are defined as those administered for 
≥14 days at a dose of ≥20 mg/day of prednisone or equivalent. Inhaled/nebulized, 
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
7. 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 60 days before study intervention administration or planned 
receipt throughout the study.
Prior/Concurrent Clinical Study Experience:
8. Participation in other studies involving receipt of a study intervention within 28 days 
before randomization. Anticipated participation in other studies involving a study 
intervention from randomization through the end of this study.
Other Exclusion Criteria:
9. 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.
Other Medical Conditions: From protocol amendment 6 (Cohort 4) onwards:
10. History of myocarditis or pericarditis.
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 
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. 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 or participant’s 
parent(s)/legal guardian 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.
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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.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Administration of 
Study Intervention
The following conditions may allow a participant to receive study intervention 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.
1. A positive SARS-CoV-2 test result (NAAT or rapid antigen test) within the previous 
28 days.
2. Current febrile illness (body temperature ≥38.0°C [≥100.4°F]) or other acute illness 
within 48 hours before study intervention administration.  This includes symptoms that 
could represent a potential COVID-19 illness (refer to Section 8.10.7).
Note: The participant should be directed to seek additional testing through his/her 
primary healthcare provider at a licensed clinical laboratory when exhibiting potential 
COVID-19 symptoms or otherwise receiving a positive result from local testing and 
counseled on whether to take any precautionary measures pending confirmatory testing, 
as per local guidance.
3. Receipt of any seasonal or pandemic influenza vaccine within 14 days, or any other 
nonstudy vaccine within 28 days, before study intervention administration.
4. Anticipated receipt of any seasonal or pandemic influenza vaccine within 14 days, or any 
other nonstudy vaccine within 28 days, after study intervention administration.
5. Receipt of short-term (<14 days) systemic corticosteroids.  Study intervention
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 28 days.  Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or 
eyes) corticosteroids are permitted.
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6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study interventions are all prespecified investigational products, medical devices, and other 
interventions (eg, surgical and behavioral) intended to be administered to the study 
participants during the study conduct.
For the purposes of this protocol, study intervention refers to investigational product.
6.1. Study Interventions Administered
Cohort 1

BNT162b5 Bivalent (WT/OMI BA.2) =
BNT162b5 Wild Type and BNT162b5 OMICRON (B.1.1.529) sublineage BA.2
(BNT162b5 RNA-LNP vaccine utilizing modRNA and encoding the P6’ S)

BNT162b2 Bivalent (WT/OMI BA.1) =
BNT162b2 Wild Type and BNT162b2 OMICRON (B.1.1.529) sublineage BA.1
(BNT162b2 RNA-LNP vaccine utilizing modRNA and encoding the P2 S)
Study Interventions – Cohort 1
Intervention Name
BNT162b5 Bivalent (WT/OMI BA.2)
(BNT162b5 Wild Typea and 
BNT162b5 OMICRON 
[B.1.1.529 sublineage BA.2])
Preformulated as a single vial 
(no dilution required)
BNT162b2 Bivalent (WT/OMI BA.1)
(BNT162b2 Wild Typea and 
BNT162b2 OMICRON
[B.1.1.529 sublineage BA.1])
Preformulated as a single vial 
(no dilution required)
Arm Name
(group of participants 
receiving a specific study 
intervention or no study 
intervention)
BNT162b5 Bivalent (WT/OMI BA.2)
BNT162b2 Bivalent (WT/OMI BA.1)
Type
Vaccine
Vaccine
Dose Formulation
Multidose vialb
Multidose vialb
Unit Dose Strength(s)
100 µg/mL
100 µg/mL
Dosage Level(s)
30 µg 
(15 µg BNT162b5 Wild Typea and
15 µg BNT162b5 OMICRON 
[B.1.1.529 sublineage BA.2])
30 µg 
(15 µg BNT162b2 Wild Typea and
15 µg BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.1])
Route of Administration
Intramuscular injection
Intramuscular injection
Use
Experimental 
Experimental and active comparator
IMP or NIMP/AxMP
IMP
IMP
Sourcing
Provided centrally by Pfizer
Provided centrally by Pfizer
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Study Interventions – Cohort 1
Packaging and Labeling
Study intervention will be provided in a 
glass vial as open-label supply. Vials
will be labeled as required per country 
requirement.
Study intervention will be provided in a 
glass vial as open-label supply. Vials
will be labeled as required per country 
requirement.
a.
Wild Type refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol 
as the Original or reference strain.
b.
Study intervention will be administered as a single dose from multidose vials.
Study Arms – Cohort 1
Arm Title
BNT162b5 Bivalent (WT/OMI BA.2)
BNT162b2 Bivalent (WT/OMI BA.1)
Arm Type
Experimental
Experimental and active comparator
Arm Description
Participants will receive 30 µg of 
BNT162b5 Bivalent (WT/OMI BA.2) 
at Visit 1.
Participants will receive 30 µg of 
BNT162b2 Bivalent (WT/OMI BA.1)
at Visit 1.
Associated Intervention 
Labels
BNT162b5 Bivalent (WT/OMI BA.2)
(BNT162b5 Wild Type and 
BNT162b5 OMICRON 
[B.1.1.529 sublineage BA.2])
BNT162b2 Bivalent (WT/OMI BA.1)
(BNT162b2 Wild Type and 
BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.1])
Cohort 2

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) =
BNT162b2 Wild Type and BNT162b2 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b2 RNA-LNP vaccine utilizing modRNA and encoding the P2 S)
Study Interventions – Cohort 2
Intervention Name
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 
(BNT162b2 Wild Typea and BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.4/BA.5])
Preformulated as a single vial (no dilution required)
Arm Name
(group of participants receiving a 
specific study intervention or no study 
intervention)
BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
Type
Vaccine
Dose Formulation
Multidose vialb
Unit Dose Strength(s)
100 µg/mL
Dosage Level(s)
30 µg or 60 µg
(15 µg BNT162b2 Wild Type and 
15 µg BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5])
(30 µg BNT162b2 Wild Type and 
30 µg BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5])
Route of Administration
Intramuscular injection
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Study Interventions – Cohort 2
Use
Experimental 
IMP or NIMP/AxMP
IMP
Sourcing
Provided centrally by Pfizer
Packaging and Labeling
Study intervention will be provided in a glass vial as open-label 
supply. Vials will be labeled as required per country requirement.
a.
Wild Type refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol 
as the Original or reference strain.
b.
Study intervention will be administered as a single dose from multidose vials.
Study Arms – Cohort 2
Arm Title
Group 1:
12-17 years, 
30 µg
Group 2: 
18-55 years, 
30 µg
Group 3:
18-55 years, 
60 µg
Group 4:
55 years, 
30 µg
Group 5:
>55 years, 
60 µg
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm 
Description
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
30 µg at Visit 1
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
30 µg at Visit 1
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
60 µg at Visit 1
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
30 µg at Visit 1
Participants will 
receive 
BNT162b2 
Bivalent 
(WT/OMI 
BA.4/BA.5) 
60 µg at Visit 1
Associated 
Intervention 
Label
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 
(BNT162b2 Wild Typea and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5])
a.
Wild Type refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol 
as the Original or reference strain.
Cohort 3

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) =
BNT162b2 Wild Type and BNT162b2 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b2 RNA-LNP vaccine utilizing modRNA and encoding the P2 S)
Study Interventions – Cohort 3
Intervention Name
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 
(BNT162b2 Wild Typea and BNT162b2 OMICRON 
[B.1.1.529 sublineage BA.4/BA.5])
Preformulated as a single vial (no dilution required)
Arm Name 
(group of participants receiving a specific 
study intervention or no study 
intervention)
BNT162b2 Bivalent (WT/OMI BA.4/BA.5)
Type
Vaccine
Dose Formulation
Multidose vialb
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Study Interventions – Cohort 3
Unit Dose Strength(s)
100 µg/mL
Dosage Level(s)
30 µg 
(15 µg BNT162b2 Wild Type and 
15 µg BNT162b2 OMICRON [B.1.1.529 sublineage 
BA.4/BA.5])
Route of Administration
Intramuscular injection
Use
Experimental 
IMP or NIMP/AxMP
IMP
Sourcing
Provided centrally by Pfizer
Packaging and Labeling
Study intervention will be provided in a glass vial as open-label 
supply. Vials will be labeled as required per country 
requirement.
a.
Wild Type refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol 
as the Original or reference strain.
b.
Study intervention will be administered as a single dose from multidose vials.
Study Arms – Cohort 3
Arm Title
Group 1: 18-55 years of age, 30 µg
Group 2: >55 years of age, 30 µg
Arm Type
Experimental
Experimental 
Arm Description
Participants will receive BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 30 µg 
at Visit 1
Participants will receive BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 30 µg 
at Visit 1
Associated Intervention 
Label
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 
(BNT162b2 Wild Typea and BNT162b2 OMICRON [B.1.1.529 sublineage 
BA.4/BA.5])
a.
Wild Type refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol 
as the Original or reference strain.
Cohort 4
The Cohort 4 bivalent vaccine names use “Original” instead of “Wild Type” (or “WT”).  
Both terms refer to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), which is also 
referred to in this protocol as the reference strain. Study intervention labeling may contain 
“Wild Type/WT” or “Original” interchangeably.

BNT162b2 Bivalent (Original/OMI BA.4/BA.5) =
BNT162b2 Original and BNT162b2 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b2 RNA-LNP vaccine utilizing modRNA and encoding the P2 S)

BNT162b5 Bivalent (Original/OMI BA.4/BA.5) =
BNT162b5 Original and BNT162b5 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b5 RNA-LNP vaccine utilizing modRNA and encoding the P6’ S)
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
BNT162b6 Bivalent (Original/OMI BA.4/BA.5) =
BNT162b6 Original and BNT162b6 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b6 RNA-LNP vaccine utilizing modRNA for the P6 S)

BNT162b7 Bivalent (Original/OMI BA.4/BA.5) =
BNT162b7 Original and BNT162b7 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b7 RNA-LNP vaccine utilizing modRNA for the P6 S)

BNT162b7 Monovalent (OMI BA.4/BA.5) =
BNT162b7 OMICRON (B.1.1.529) sublineage BA.4/BA.5
(BNT162b7 RNA-LNP vaccine utilizing modRNA for the P6 S)
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Study Interventions – Cohort 4
Intervention Name
BNT162b2 Bivalent 
(Original/OMI BA.4/BA.5)
(BNT162b2 Originala and 
BNT162b2 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5]) Preformulated 
in a single vial (no dilution 
required)
BNT162b5 Bivalent 
(Original/OMI BA.4/BA.5)
(BNT162b5 Originala and 
BNT162b5 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5]) Preformulated 
in a single vial (no dilution 
required)
BNT162b6 Bivalent 
(Original/OMI BA.4/BA.5)
(BNT162b6 Originala and 
BNT162b6 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5]) Preformulated 
in a single vial (no dilution 
required)
BNT162b7 Bivalent 
(Original/OMI BA.4/BA.5)
(BNT162b7 Originala and 
BNT162b7 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
Preformulated in a single 
vial (no dilution required)
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
(BNT162b7 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
Preformulated in a single 
vial (no dilution required)
Arm Name
(group of participants 
receiving a specific study 
intervention or no study 
intervention)
BNT162b2 Bivalent 
(Original/
OMI BA.4/BA.5)
BNT162b5 Bivalent 
(Original/
OMI BA.4/BA.5)
BNT162b6 Bivalent 
(Original/OMI BA.4/BA.5)
BNT162b7 Bivalent 
(Original/
OMI BA.4/BA.5)
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
Type
Vaccine
Vaccine
Vaccine
Vaccine
Vaccine
Dose Formulation
modRNA
modRNA
modRNA
modRNA
modRNA
Unit Dose Strength(s)
100 µg/mL
100 µg/mL
100 µg/mL
100 µg/mL
100 µg/mL
Dosage Level(s)
30 µg 
(15 µg BNT162b2 Original 
and 15 µg BNT162b2 
OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
30 µg 
(15 µg BNT162b5 Original 
and 15 µg BNT162b5 
OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
30 µg 
(15 µg BNT162b6 Original 
and 15 µg BNT162b6 
OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
30 µg 
(15 µg BNT162b7 Original 
and 15 µg BNT162b7 
OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
30 µg 
(30 µg BNT162b7 
OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
Route of Administration
Intramuscular injection
Intramuscular injection
Intramuscular injection
Intramuscular injection
Intramuscular injection
Use
Active comparator 
Experimental
Experimental
Experimental
Experimental
IMP or NIMP/AxMP
IMP
IMP
IMP
IMP
IMP
Sourcing
Provided centrally by Pfizer Provided centrally by Pfizer Provided centrally by Pfizer Provided centrally by Pfizer Provided centrally by Pfizer
Packaging and Labeling
Study intervention will be 
provided in multidose glass 
vials for single use as 
open-label supply.  Vials 
will be labeled as required 
per country requirement.
Study intervention will be 
provided in multidose glass 
vials for single use as 
open-label supply.  Vials 
will be labeled as required 
per country requirement.
Study intervention will be 
provided multidose glass 
vials for single use as 
open-label supply.  Vials 
will be labeled as required 
per country requirement.
Study intervention will be 
provided in multidose glass 
vials for single use as 
open-label supply.  Vials 
will be labeled as required 
per country requirement.
Study intervention will be 
provided in multidose glass 
vials for single use as 
open-label supply.  Vials 
will be labeled as required 
per country requirement.
a.
Original refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol as Wild Type, WT, and the reference strain. Study
intervention vial labels for the Cohort 4 bivalent vaccines may specify WT instead of Original.
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Study Arms – Cohort 4
Arm Title
BNT162b2 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b5 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b6 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b7 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
Arm Type
Active comparator 
Experimental
Experimental
Experimental
Experimental
Arm Description
Participants will receive 
BNT162b2 Bivalent 
(Original/
OMI BA.4/BA.5) 30 µg 
at Visit 1.
Participants will receive 
BNT162b5 Bivalent 
(Original/
OMI BA.4/BA.5) 30 µg 
at Visit 1.
Participants will receive 
BNT162b6 Bivalent 
(Original/OMI 
BA.4/BA.5) 30 µg at 
Visit 1.
Participants will receive 
BNT162b7 Bivalent 
(Original/
OMI BA.4/BA.5) 30 µg 
at Visit 1.
Participants will receive 
BNT162b7 Monovalent 
(OMI BA.4/BA.5) 30 µg 
at Visit 1.
Associated Intervention 
Label
BNT162b2 Bivalent 
(Originala/OMI 
BA.4/BA.5)
(BNT162b2 Original and 
BNT162b2
OMICRON [B.1.1.529
sublineage BA.4/BA.5])
BNT162b5 Bivalent 
(Originala/OMI 
BA.4/BA.5)
(BNT162b5 Original and 
BNT162b5
OMICRON [B.1.1.529
sublineage BA.4/BA.5])
BNT162b6 Bivalent 
(Originala/OMI 
BA.4/BA.5)
(BNT162b6 Original and 
BNT162b6 OMICRON 
[B.1.1.529
sublineage BA.4/BA.5])
BNT162b7 Bivalent 
(Originala/OMI 
BA.4/BA.5)
(BNT162b7 Original and 
BNT162b7
OMICRON [B.1.1.529
sublineage BA.4/BA.5])
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
(BNT162b7 OMICRON 
[B.1.1.529 sublineage 
BA.4/BA.5])
a.
Original refers to the ancestral strain (Wuhan-Hu-1; USA-WA1/2020), also referred to in this protocol as Wild Type, WT, and the reference strain.  Study 
intervention vial labels for the Cohort 4 bivalent vaccines may specify WT instead of Original.
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6.1.1. Administration
Participants will receive 1 dose of study intervention as allocated by the IRT at Visit 1 in 
accordance with the study’s SoA (Section 1.3).
Study intervention should be administered intramuscularly into the deltoid muscle, preferably 
of the nondominant arm. The volume to be administered may vary by dose level; full details 
are described in the IPM.
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels. Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of study interventions should 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.
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. 
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.
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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 once 
prepared.
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 for instructions on how to prepare the study intervention for administration. 
Study intervention should be prepared and dispensed by an appropriately qualified and 
experienced member of the study staff (eg, physician, nurse, physician’s assistant, nurse 
practitioner, pharmacy assistant/technician, or pharmacist) as allowed by local, state, and 
institutional guidance. A second staff member will verify the dispensing.
Study intervention will be prepared by qualified unblinded site personnel according to the 
IPM. The study intervention will be administered by unblinded study staff to all participants.
Study intervention will be provided in multidose vials; however, they are intended for single 
use, as outlined in the IPM.
6.3. Assignment to Study Intervention
Allocation (randomization) of participants to vaccine groups will proceed through the use of 
an IRT system, including Group 1 of Cohort 2 (12 through 17 years of age) and the Cohort 3 
groups, all receiving 30 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5). Participants in 
Cohort 1 will be randomized 1:1 to receive either BNT162b5 Bivalent (WT/OMI BA.2) 
30 µg or BNT162b2 Bivalent (WT/OMI BA.1) 30 µg. Participants 18 through 55 and 
55 years of age in Cohort 2 will be randomized 1:1 within each age group to receive 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at either 30 µg or 60 µg. Participants in Cohort 4 
will be randomized 1:1:1:1:1 (see Table 4). The site personnel (study coordinator or specified 
designee) will be required to enter or select information including but not limited to the 
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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 vaccine 
group, and DU or container number(s) when study intervention is being supplied via the IRT 
system. The IRT system will provide a confirmation report containing the participant 
number, randomization number, and DU or container number assigned. The confirmation 
report must be stored in the site’s files.
Participants will be stratified in Cohort 1 by the number of months since the last dose of the 
COVID-19 vaccine received prior to entering the study (3 to 6 months [90 to 180 days] or 
>6 months [>180 days]). Participants will be stratified in Cohort 4 by the number of prior 
doses of a COVID-19 mRNA vaccine received (3 or 4 prior doses) prior to randomization.
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
Cohort 1: This cohort will be observer-blind at the site level with respect to study 
intervention allocation and open-label to most Pfizer staff.  Refer to Section 6.4.3.
Cohort 2: Participants 18 through 55 and 55 years of age receiving the second booster: 
These participant groups will be observer-blind at the site level with respect to study 
intervention allocation (dose of BNT162b2 [WT/OMI BA.4/BA.5]) and open-label to most 
Pfizer staff.
Participants 12 through 17 years of age receiving the second booster: This participant group
is open-label. Refer to Table 1.
Cohort 3: Both participant groups (18 through 55 years of age and 55 years of age)
receiving the second booster are open-label. Refer to Table 3.
Cohort 4: This cohort will be observer-blind at the site level with respect to study 
intervention allocation and open-label to most Pfizer staff.
6.4.1. Blinding of Participants
Cohort 1: Participants will be blinded to their assigned study intervention.
Cohort 2: Participants 12 through 17 years of age receiving the second booster will not be 
blinded to study intervention. Participants 18 through 55 and 55 years of age receiving the 
second booster will be blinded to the dose of BNT162b2 (WT/OMI BA.4/BA.5).
Cohort 3: All participants receiving the second booster will not be blinded to study 
intervention.
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Cohort 4: Participants will be blinded to their assigned study intervention.
Where applicable, participants will be unblinded at a time decided by Pfizer.
6.4.2. Blinding of Site Personnel
Although Cohort 2 has an open-label group (12 through 17 years of age receiving their 
second booster) and both Cohort 3 groups are open-label, the following instructions for site 
personnel applies to all participants in order to maintain the blinding for the other 
cohorts/groups:
In this observer-blind study, the study staff receiving, storing, dispensing, preparing, and 
administering the study interventions will be unblinded. All other study and site personnel, 
including the investigator, investigator staff, and participants, will be blinded to study 
intervention assignments. In particular, the individuals who evaluate participant safety will 
be blinded. Because there may be differences in physical appearance of the study 
interventions, the study intervention will be administered in a manner that prevents the study 
participants from identifying the study intervention group based on its appearance.
The PI will assign the responsibility of the unblinded dispensers/administrators to persons 
who will not participate in the evaluation of any study participant. To ensure adequate 
coverage, at least 2 unblinded dispensers/administrators will be assigned per site. Members 
of the study site staff or clinic pharmacy should fulfill these roles. Contact between the 
unblinded dispensers and study participants should be kept to a minimum. The investigator, 
study coordinator, and any site staff other than the unblinded dispensers/administrators must 
not be allowed to know the study intervention assigned to any study participant and must not 
be allowed to see the study intervention container contents.
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the site(s) to verify that randomization/dispensing has been done 
accurately.
The study will be unblinded to site personnel at a time decided by Pfizer.
6.4.3. Blinding of the Sponsor
Cohort 1, Cohort 2, and Cohort 4: To facilitate rapid review of data in real time, the majority 
of Pfizer/BioNTech staff will be unblinded to study intervention allocation.
Cohort 3: Given the single study intervention arm, both groups are unblinded to the majority 
of Pfizer staff involved in the conduct of the study.
All Cohorts: All laboratory testing personnel will remain blinded to study intervention 
assigned/received throughout the study.
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As this is a sponsor open-label study, the sponsor may conduct unblinded reviews of the data 
during the course of the study for the purpose of safety assessment and/or supporting clinical 
development.
6.4.4. Breaking the Blind 
Emergency blind-break: The IRT will be programmed with blind-breaking instructions. In 
case of an emergency, the investigator has the sole responsibility for determining if 
unblinding of a participant’s vaccine assignment is warranted. Participant safety must 
always be the first consideration in making such a determination. If the investigator decides 
that unblinding is warranted, the investigator should make every effort to contact the study 
medical monitor prior to unblinding a participant’s vaccine assignment unless this could 
delay further management of the participant. If a participant’s vaccine assignment is 
unblinded, Pfizer must be notified within 24 hours after breaking the blind. The date and 
reason that the blind was broken must be recorded in the source documentation and CRF.
The study-specific IRT reference manual and IPM will provide the contact information and 
further details on the use of the IRT system.
Pfizer-defined unblinding time point: Unblinding at the sponsor-defined unblinding time 
point (refer to Section 6.4.1) is not done via the IRT system but rather through a procedure
detailed in the IPM. The date and reason that the blind was broken must be recorded in the 
source documentation and on a form provided in the IPM but is not required to be recorded 
in the CRF.
6.5. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
unblinded 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 ID will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study intervention.
The site will complete the required dosage Preparation Record located in the IPM. The use 
of the Preparation Record is preferred, but it does not preclude the use of an existing 
appropriate clinical site documentation system. The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose. This may be used in place of the Preparation Record after 
approval from Pfizer and/or designee.
6.6. Dose Modification 
Not applicable to this study.
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.
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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 at least 
until the next scheduled follow-up.
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 prior and concomitant medications and vaccinations will be recorded in the 
CRF:

Prohibited medications listed in Section 6.9.1 will be recorded in the concomitant 
medication CRF, with the exception of prophylactic antipyretics and other pain 
medication to prevent symptoms.

All vaccinations received from 28 days prior to study enrollment until the 6-month 
follow-up visit will be recorded in the nonstudy vaccination CRF.

All prior COVID-19 vaccinations will be recorded in the prior COVID-19 vaccination 
CRF.

Any prescribed medication to treat or intended to treat COVID-19/MIS-C illness, 
including receipt of antiplatelets (eg, aspirin, clopidogrel) or anticoagulants (eg, heparin, 
enoxaparin, warfarin), will be recorded in the concomitant medication CRF within the 
COVID-19 illness visit.
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 (unless documented 
as per Section 7.2). Medications should not be withheld if required for a participant’s 
medical care.
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
Unless considered medically necessary, no vaccines other than study intervention should 
be administered within 28 days before and 28 days after each study vaccination. With the 
exception of seasonal and pandemic influenza vaccine that can be given at least 14 days 
after, or at least 14 days prior to, the administration of study intervention.

Receipt of chronic systemic treatment with known immunosuppressant medications
(including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days 
before enrollment through conclusion of the study.
Note: Chronic systemic corticosteroids are defined as those administered for ≥14 days 
at a dose of ≥20 mg/day of prednisone or equivalent.

Receipt of systemic corticosteroids for <14 days is prohibited from 28 days prior to 
administration of study intervention and through 28 days after administration of study 
intervention.

Receipt of blood/plasma products, immunoglobulins, or monoclonal antibodies used for 
the treatment or prevention of COVID-19, or those that are considered 
immunosuppressive, from 60 days before study intervention administration through 
conclusion of the study.

Receipt of any other (nonstudy) coronavirus vaccine at any time during study 
participation.

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

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.
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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Since this is a single-dose study, this section is not applicable.
7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at their own request or request of the 
participant’s parent(s)/legal guardian. The participant will be permanently discontinued from 
the study at that time. Reasons for discontinuation from the study include the following:

Lost to follow-up;

Death;

Study terminated by Pfizer;

AEs;

Participant/participant’s parent(s)/legal guardian request; 

Investigator request;

Select protocol deviations (Note: receipt of a COVID-19 vaccine outside of the study will 
result in study withdrawal).
If a participant withdraws from the study, they or the participant’s parent(s)/legal guardian
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 Pfizer 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. Pfizer may retain and continue to use any data collected 
before such withdrawal of consent.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue active study participation (eg, biological sample 
collection or surveillance for disease endpoints) will remain in the study and must continue to 
be followed for protocol-specified safety follow-up procedures. The only exception to this is 
when a participant or participant’s parent(s)/legal guardian specifically withdraws 
consent/assent for any further contact with him or her or persons previously authorized by the 
participant to provide this information. Participants or participants’ parent(s)/legal guardian
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 
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the medical records by the investigator, as to whether the withdrawal is only from specified 
study procedures and/or postvaccination safety 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 return to the clinic for a required 
study visit:

The site must attempt to contact the participant or participant’s parent(s)/legal guardian 
and reschedule the missed visit as soon as possible. Counsel the participant or 
participant’s parent(s)/legal guardian 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 or participant’s parent(s)/legal guardian 
(where possible, 3 telephone calls and, if necessary, a certified letter to the participant’s 
last known mailing address or local equivalent methods). These contact attempts should 
be documented in the participant’s medical record;

Should the participant or participant’s parent(s)/legal guardian continue to be 
unreachable, the participant will be considered to have withdrawn from the study.
8. STUDY ASSESSMENTS AND PROCEDURES
8.1. Administrative and Baseline Procedures
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
The date of birth will be collected to critically evaluate the immune response and safety 
profile by age.
A participant number will be assigned.
A randomization number and study intervention allocation will be obtained from the IRT 
system.
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.
Safety and laboratory results that have been collected for the purposes of this study and could 
unblind the study will not be reported to investigative sites or other blinded personnel until 
the study has been unblinded.
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 at scheduled visits in this study 
is approximately 160 mL for participants ≥18 years of age and 50 mL for participants 
12 through 17 years of age. Those participants ≥18 years of age in Cohort 2 who consent to 
additional blood collection for isolation of PBMCs will have a total blood sampling volume 
of up to approximately 815 mL. Additionally, 20 mL of blood for participants ≥18 years of 
age and 10 mL for participants 12 through 17 years of age will be taken at an unplanned 
in-person potential COVID-19 illness visit and at an unplanned COVID-19 convalescent 
visit, conducted 28 to 35 days following the illness visit, with the illness visit completed at 
any time a participant develops symptoms indicating potential COVID-19. 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 for participants 18 years of age and older.
8.1.1. Baseline Procedures 
The baseline procedures (not detailed in subsequent sections) are listed below. They are 
performed at Visit 1 (Day 1):

Record demography data (including date of birth, sex, race, and ethnicity).
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
Record any medical history of clinical significance, including confirmed COVID-19 
diagnosis or asymptomatic positive SARS-CoV-2 test result (NAAT or antigen test).

Measure and record height and weight.
8.2. Efficacy and/or Immunogenicity Assessments
8.2.1. Surveillance for COVID-19
Surveillance for potential cases of COVID-19 and MIS-C will occur throughout a 
participant’s involvement in the study to describe both COVID-19 (all participants) and 
MIS-C (participants <21 years of age). If, at any time, a participant develops acute 
respiratory illness (see Section 8.10.7), for the purposes of the study he or she will be 
considered to potentially have COVID-19. In this circumstance, the participant or 
participant’s parent(s)/legal guardian should contact the site, an in-person or telehealth visit 
should occur, and assessments should be conducted as specified in the SoA. The assessments 
will include a nasal (midturbinate) swab, which will be tested at a central laboratory using an
RT-PCR test (Cepheid; FDA approved under EUA), or other equivalent nucleic acid 
amplification–based test (ie, NAAT), to detect SARS-CoV-2. In addition, clinical 
information and results from local standard-of-care tests (as detailed in Section 8.10.8) will 
be assessed. The central laboratory NAAT result will be used for the case definition, unless 
no result is available from the central laboratory, in which case a local NAAT result may be 
used if it was obtained using 1 of the following assays:

Cepheid Xpert Xpress SARS-CoV-2

Roche cobas SARS-CoV-2 real-time RT-PCR test (EUA200009/A001)

Abbott Molecular/RealTime SARS-CoV-2 assay (EUA200023/A001)
Definitions of SARS-CoV-2–related cases, and SARS-CoV-2–related severe cases, will be 
considered as follows (for both, the onset date of the case will be the date that symptoms 
were first experienced by the participant; if new symptoms are reported within 4 days after 
resolution of all previous symptoms, they will be considered as part of a single illness):

Confirmed COVID-19: presence of at least 1 of the following symptoms and 
SARS-CoV-2 NAAT positive during, or within 4 days before or after, the symptomatic 
period, either at the central laboratory or at a local testing facility 
(using an acceptable test):
o
Fever;
o
New or increased cough;
o
New or increased shortness of breath;
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o
Chills;
o
New or increased muscle pain;
o
New loss of taste or smell;
o
Sore throat;
o
Diarrhea;
o
Vomiting.

The CDC list of COVID-19 symptoms can be found at: 
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.42  The 
additional symptoms listed by the CDC (ie, those not listed in the above protocol-defined 
list) should not trigger a potential COVID-19 illness visit unless, in the opinion of the PI, 
it is deemed necessary. 

Confirmed severe COVID-19 (FDA definition43): confirmed COVID-19 and presence of 
at least 1 of the following:
o
Clinical signs at rest indicative of severe systemic illness (RR ≥30 breaths per minute, 
HR ≥125 beats per minute, SpO2 ≤93% on room air at sea level, or 
PaO2/FiO2 300 mm Hg);
o
Respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, 
mechanical ventilation, or ECMO);
o
Evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors);
o
Significant acute renal, hepatic, or neurologic dysfunction;
o
Admission to an ICU;
o
Death.

Confirmed severe COVID-19 (CDC definition44): confirmed COVID-19 and presence of 
at least 1 of the following:
o
Hospitalization;
o
Admission to the ICU;
o
Intubation or mechanical ventilation;
o
Death.
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The DMC may recommend modification of the definition of severe disease according to 
emerging information.
Confirmed MIS-C definition, as per the CDC MIS-C case definition45:

An individual <21 years of age presenting with fever (≥38.0°C for ≥24 hours or report of 
subjective fever lasting ≥24 hours); AND

Laboratory evidence of inflammation (based on local laboratory ranges) including, but 
not limited to, 1 or more of the following: Elevated CRP, ESR, fibrinogen, procalcitonin, 
D-dimer, ferritin, LDH, or IL-6, elevated neutrophils, reduced lymphocytes, and low 
albumin; AND

Evidence of clinically severe illness requiring hospitalization (definition as noted above 
for severe disease), with multisystem (≥2) organ involvement:
o
Cardiac (eg, shock, elevated troponin, elevated BNP, abnormal echocardiogram, 
arrhythmia);
o
Renal (eg, AKI);
o
Respiratory (eg, pneumonia, ARDS, pulmonary embolism);
o
Hematologic (eg, elevated D-dimers, thrombophilia, or thrombocytopenia);
o
GI/hepatic (eg, elevated bilirubin, elevated liver enzymes, or diarrhea);
o
Dermatologic (eg, rash, mucocutaneous lesions);
o
Neurological (eg, CVA, aseptic meningitis, encephalopathy); AND

No alternative plausible diagnoses; AND

Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen 
test; OR 

COVID-19 exposure within the 4 weeks prior to the onset of symptoms.
8.2.2. Vaccine-Induced Immunogenicity
Blood samples will be obtained at each visit for immunogenicity testing at the central 
laboratory. The following assays will be performed on serum samples at each visit:

SARS-CoV-2 neutralization assay (reference strain)
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
SARS-CoV-2 neutralization assays (Omicron BA.1, Omicron BA.2, Omicron BA.4, 
Omicron BA.5; other variants), including other Omicron sublineages, may also be 
evaluated)

At designated sites, optional whole blood samples of ~130 mL will be obtained from up 
to approximately 30 participants per group (≥18 years of age only) within Cohort 2 for 
evaluation of boostability and protection against Omicron and the reference strain for 
isolation of PBMCs.  These samples will be used to describe B-cell and T-cell responses 
to Omicron and the reference strain. A blood sample of ~5 mL for HLA typing will also 
be obtained.
8.2.3. N-Binding Antibody Test
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.
8.2.4. Biological Samples
Blood and nasal swab samples will be used only for scientific research.  Each sample will be 
labeled with a code so that the laboratory 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 vaccines 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, with the exception of those 
participants who have provided specific consent to genetic testing of the blood samples for 
PBMC isolation and HLA typing.
The participant or participant’s parent(s)/legal guardian 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, with the exception of those participants who have provided specific consent to 
genetic testing of the blood samples for PBMC isolation and HLA typing.
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.
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8.3.1. Physical Examinations
Perform a clinical assessment. If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, a physical examination 
will be performed.
A complete physical examination will include evaluating any clinically significant 
abnormalities within the following body systems: general appearance; skin; head, eyes, ears, 
nose, and throat; heart; lungs; abdomen; musculoskeletal; extremities; neurological; and 
lymph nodes.
Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Section 8.4.1 to Section 8.4.3.
8.3.2. Vital Signs
The participant’s body temperature will be measured at Visit 1, prior to study vaccination.
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 Section 8.4.1 to Section 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
Potential COVID-19 illness e-diary: This e-diary is used as a tool for participants to alert 
study sites of a COVID-19 diagnosis or symptoms that could represent a potential 
COVID-19 illness; it is not reported data. Participants will receive reminders to complete the 
COVID-19 illness e-diary on a weekly basis throughout the study and whenever they receive 
a diagnosis of COVID-19 or experience symptoms of COVID-19. Please refer to 
Section 8.2.1.
Reactogenicity e-diary: Participants or participants’ parent(s)/legal guardian will be required 
to complete a reactogenicity e-diary through an application installed on a provisioned device 
or on the personal device of the participant or participant’s parent(s)/legal guardian.  All 
participants or participants’ parent(s)/legal guardian will be asked to monitor and record local 
reactions, systemic events, and antipyretic medication usage for 7 days from the day of 
administration of the study intervention.  Participants will receive reminders to complete the 
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vaccination e-diary on a daily basis, starting on the day of vaccination (Day 1) through 
Day 7.  The reactogenicity e-diary allows recording of these assessments only within a fixed 
time window, thus providing the accurate representation of the participant’s experience at 
that time.  Data on local reactions 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 or participant’s 
parent(s)/legal guardian withdraws because of events reported in the e-diary, the event(s) 
should be recorded on the AE page of the CRF, regardless of whether the investigator 
considers the event(s) to be clinically significant. 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 
AE page of 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.
The investigator or designee must obtain stop dates from the participant or participant’s 
parent(s)/legal guardian for any ongoing local reactions, systemic events, or use of 
antipyretic medication on the last day that the reactogenicity e-diary was completed.  The 
stop dates should be documented in the source documents and the information entered in the 
CRF.
8.3.4.1. 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.46
8.3.4.2. Local Reactions
During the reactogenicity e-diary reporting period, participants or participants’ 
parent(s)/legal guardian will be asked to assess redness, swelling, and pain at the injection 
site and to record the symptoms in the reactogenicity e-diary.  If a local reaction persists 
beyond the end of the reactogenicity e-diary period following vaccination, the participant or 
participant’s parent(s)/legal guardian will be requested to report that information.  The 
investigator will enter this additional information in the CRF.
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 5.  Measuring device units can be converted to 
centimeters according to the following formula: 1 measuring device unit = 0.5 cm.  Pain at 
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the injection site will be assessed by the participant as absent, mild, moderate, or severe 
according to the grading scale in Table 5.
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 Pfizer. A Grade 4 reaction will be 
collected as an AE on the CRF. The event will be graded using the AE intensity grading 
scale (Section 10.3.3).
Table 5.
Local Reaction Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4a)
Pain at the injection 
site
Does not interfere 
with activity
Interferes with 
activity
Prevents daily 
activity
Emergency room 
visit or 
hospitalization for 
severe pain
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(≥21 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Swelling
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(≥21 measuring 
device units)
Necrosis
a.
Only an investigator or medically qualified person is able to classify a reaction as Grade 4; therefore, a 
confirmed Grade 4 reaction should be reported as an AE in the case report form.
8.3.4.3. Systemic Events
During the reactogenicity e-diary reporting period, participants or participants’ 
parent(s)/legal guardian will be asked to assess vomiting, diarrhea, headache, 
fatigue/tiredness, 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 6.
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 Pfizer. A Grade 4 systemic event
will be collected as an AE on the CRF. The event will be graded using the AE intensity 
grading scale (Section 10.3.3).
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Table 6.
Systemic Event Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4)
Vomiting
1-2 times in 
24 hours
>2 times in 
24 hours
Requires IV 
hydration
Emergency room visit 
or hospitalization for 
hypotensive shock
Diarrhea
2 to 3 loose stools 
in 24 hours
4 to 5 loose stools 
in 24 hours
6 or more loose stools 
in 24 hours
Emergency room visit 
or hospitalization for 
severe diarrhea
Headache
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe headache
Fatigue/tiredness
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe fatigue
Chills
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe chills
New or worsened 
muscle pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe new or worsened 
muscle pain
New or worsened 
joint pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe new or worsened 
joint pain
Abbreviation: IV = intravenous.
During the 7 days following each vaccination, potential COVID-19 symptoms that overlap 
with solicited systemic events (ie, fever, chills, new or increased muscle pain, diarrhea, 
vomiting) should be assessed by the investigator.
If, in the investigator’s opinion, the symptoms are considered more likely to be vaccine 
reactogenicity, but a participant is required to demonstrate that he or she is SARS-CoV-2–
negative, a local SARS-CoV-2 test may be performed: if the test result is positive, the 
symptoms should be recorded in the potential COVID-19 illness CRFs (with potential 
COVID-19 illness visit completed) rather than as systemic events in the reactogenicity 
e-diary (refer to Sections 8.10.7 and 8.10.8).
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8.3.4.4. Fever
In order to record information on fever, a thermometer will be given to participants or 
participants’ parent(s)/legal guardian with instructions on how to measure oral temperature at 
home.  Temperature will be collected in the reactogenicity e-diary in the evening daily during 
the reactogenicity e-diary reporting period.  It will also be collected at any time during the 
reactogenicity e-diary data collection periods when fever is suspected.  Fever is defined as an 
oral temperature of ≥38.0°C (≥100.4°F).  The highest temperature for each day will be 
recorded in the reactogenicity e-diary.  Temperature will be measured and recorded to 
1 decimal place.  Temperatures recorded in degrees Fahrenheit will be programmatically 
converted to degrees Celsius and then categorized according to the scale shown in Table 7
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 Pfizer. Fevers >40.0°C 
(>104.0°F) will be collected as an AE on the CRF and assessed by the investigator using the 
AE intensity grading scale (Section 10.3.3).
Table 7.
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)
8.3.4.5. Antipyretic/Analgesic Medication
The use of antipyretic/analgesic medication to treat symptoms associated with study 
intervention administration will be recorded in the reactogenicity e-diary daily during the 
reporting period (Day 1 through Day 7).
8.3.5. Pregnancy Testing
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 Visit 1, before the 
administration of the study intervention dose. A negative pregnancy test result will be 
required prior to the participant’s 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 not be administered the study intervention 
dose and will be withdrawn from the study.
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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 
from the study (see Section 7.1).
During the active collection period as described in Section 8.4.1, each participant or 
participant’s parent(s)/legal guardian will be questioned about the occurrence of AEs in a 
nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.4.1. 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 or participant’s 
parent(s)/legal guardian 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 3 (approximately 1 month 
after the participant’s study vaccination).
In addition, any AE occurring up to 48 hours after any subsequent blood draw or nasal swab 
collection must be recorded on the CRF.
SAEs will be collected from the time the participant or participant’s parent(s)/legal guardian 
provides informed consent through Visit 5 (approximately 6 months after the participant’s 
study 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.
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If the participant or participant’s parent(s)/legal guardian 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 the study because of an 
AE or SAE, the AE or SAE must be recorded on the CRF and the SAE reported via PSSA or
using the Vaccine SAE Report Form.
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any 
SAE, including a death, at any time after a participant has completed the study, and they 
consider the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer via PSSA or using the Vaccine SAE Report Form.
8.4.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period (through 
approximately 6 months after the participant’s study vaccination) as described in
Section 8.4.1 are reported to Pfizer Safety via PSSA or using the Vaccine SAE Report Form
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 or participant’s parent(s)/legal guardian.
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 or participant’s parent(s)/legal guardian is 
the preferred method to inquire about AE occurrences.
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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.
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.
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8.4.5.1. Exposure During Pregnancy
An EDP occurs if:

A female participant is found to be pregnant within 28 days after receiving study
intervention.

A male participant inseminates a female partner within 28 days after receiving study 
intervention.  

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 needlestick injury, inhalation, or 
skin contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by needlestick injury, inhalation, or skin contact then exposes his female 
partner prior to or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy).

If EDP occurs in a participant or a participant’s partner, the investigator must report this 
information to Pfizer Safety via PSSA or using the Vaccine SAE Report Form and an 
EDP Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until 28 days after the 
study intervention. Beyond 28 days after the study intervention, any pregnancy that 
occurs will not be considered EDP for this study.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety via PSSA or using the Vaccine SAE Report Form and EDP 
Supplemental Form. Since the exposure information does not pertain to the participant 
enrolled in the study, the information is not recorded on a CRF; however, a copy of the 
completed 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 
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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. 
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 within 28 days after receiving the 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 needlestick 
injury, 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
via PSSA or using the Vaccine SAE Report Form. When EDB occurs in the setting of 
environmental exposure, the exposure information does not pertain to the participant enrolled 
in the study, so the information is not recorded on a CRF. However, a copy of the completed 
report is maintained in the investigator site file.
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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 via PSSA or using the Vaccine SAE Report Form, 
regardless of whether there is an associated SAE. Since the information about the 
occupational exposure does not pertain to a participant enrolled in the study, the information 
is not recorded on a CRF; however, a copy of the completed report must be maintained in the 
investigator site file.
8.4.6. Cardiovascular and Death Events
Not applicable.
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
A potential COVID-19/MIS-C illness visit, potential COVID-19 illnesses, and their sequelae 
should not be recorded as AEs, with the exception of those assessed by the investigator as 
related to the study intervention or those meeting the criteria for SAEs.  These data will be 
captured as efficacy assessment data only on the relevant pages of the CRF, as these are 
expected endpoints.
Through protocol amendment 2: Potential COVID-19 illnesses and their sequelae will not be 
reported according to the standard process for expedited reporting of SAEs, even though the 
event may meet the definition of an SAE.  These events will be recorded on the COVID-19 
illness pages in the participant’s CRF within 1 day.
Note: However, if either of the following conditions applies, then the event must be recorded 
and reported as an SAE (instead of a DRE):

The event is, in the investigator’s opinion, of greater intensity, frequency, or duration 
than expected for the individual participant.
OR

The investigator considers that there is a reasonable possibility that the event was 
related to study intervention.
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Potential COVID-19 illness events and their sequelae will be reviewed by a group of internal 
case reviewers.  Any SAE that is determined by the internal case reviewers NOT to meet 
endpoint criteria is reported back to the investigator site of incidence.  The investigator must 
report the SAE to Pfizer Safety within 24 hours of being made aware that the SAE did not 
meet endpoint criteria.  The investigator’s SAE awareness date is the date on which the 
investigator site of incidence receives the SAE back from the internal case reviewers.
From protocol amendment 4: All SAEs occurring in a participant during the active collection 
period as described in Section 8.4.1 are reported to Pfizer Safety via PSSA or using the 
Vaccine SAE Report Form immediately upon awareness, and under no circumstance should 
this exceed 24 hours, as indicated in Appendix 3. This includes potential COVID-19 
illnesses and their sequelae that meet the definition of an SAE. 
8.4.8. Adverse Events of Special Interest
Myocarditis and pericarditis, if reported, have additional procedures associated with their 
evaluation; they are, therefore, considered protocol-specified AESIs:

Prior to Cohort 4: Confirmed diagnosis of myocarditis or pericarditis occurring within 4 
weeks after vaccination.  See Section 8.10.11.

From Cohort 4 onwards: Confirmed diagnosis of myocarditis or pericarditis occurring 
within 6 weeks after vaccination. See Section 8.10.11.
Prior to Cohort 4: 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 via PSSA or using the 
Vaccine SAE Report Form.
From Cohort 4 onwards: Any diagnosis of myocarditis or pericarditis is considered an 
important medical event and must be reported as an SAE via PSSA or using the Vaccine 
SAE Report Form (refer to Section 8.4.1.1). Other diagnoses should be recorded as AEs or 
SAEs, as appropriate. Refer to Section 8.4.3 for information regarding follow-up of AEs and 
SAEs.
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.
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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
Not applicable.
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 
Vaccination Error Page 
of the CRF
Recorded on the 
Adverse Event Page 
of the CRF
Reported via PSSA or on 
the Vaccine SAE Report
Form 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.
Such vaccination errors occurring to a study participant are to be captured on the vaccination 
error page of the CRF, which is a specific version of the AE page.
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Whether or not the vaccination error is accompanied by an AE, as determined by the 
investigator, the vaccination error is recorded on the vaccination error page of the CRF and, 
if applicable, any associated AE(s), serious and nonserious, 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 via PSSA or using a 
Vaccine SAE Report Form only when associated with an SAE.
8.5. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study.
8.6. Genetics
Some of the blood samples collected for PBMC isolation and HLA typing may be used for 
DNA and/or RNA isolation. The DNA and/or RNA samples from the PBMC isolation may 
be used for sequencing of participants’ antibody and/or BCR heavy- and light-chain genes, 
TCR genes, and/or mRNAs, for understanding the B-cell, T-cell, and antibody repertoires. 
The DNA and/or RNA samples from the blood sample for HLA typing may be used to 
further characterize HLA type. 
See Appendix 5 (Section 10.5) for information regarding genetic research. Details on 
processes for collection and shipment of these samples will be provided separately.
8.7. Biomarkers
Biomarkers are not evaluated in this study.
8.8. Immunogenicity Assessments
Immunogenicity assessments are described in 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 – Study Intervention Administration – Day 1

Before enrollment and before any study-related procedures are performed, voluntary, 
written, study-specific informed consent and assent, if appropriate, will be obtained from 
the participant and/or participant’s parent(s)/legal guardian. 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
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and/or participant’s parent(s)/legal guardian. The source data must reflect that the 
informed consent was obtained before participation in the study.
It is anticipated that the procedures below will be conducted in a stepwise manner.  Ensure 
that procedures listed prior to administration of the vaccine are conducted prior to 
vaccination and on the day of the vaccination.

Assign a participant number using the IRT system.  If the participant is from a prior 
Pfizer COVID-19 study, record the participant number of the prior study in the CRF. If 
the participant has participated in more than 1 prior Pfizer COVID-19 study, record the 
participant numbers of both the most recent prior study and the first study in the CRF.

Obtain the participant’s demography (including date of birth, sex, race, and ethnicity).  
The full date of birth will be collected to critically evaluate the immune response and 
safety profile by age.

Obtain medical history, including confirmed COVID-19 diagnosis or asymptomatic 
positive SARS-CoV-2 test result (NAAT or antigen test), and any other medical history 
of clinical significance.

Review documentation of all prior COVID-19 vaccinations. All vaccines must be 
authorized for use in the US for participants enrolled in Cohort 1. All prior vaccines 
must be 30-µg doses of BNT162b2 for participants enrolled in Cohort 2 and Cohort 3.  
For Cohort 4, all prior vaccines must be mRNA vaccines (and dose levels) authorized for 
use in the US, with the last dose being a US-authorized Omicron BA.4/BA.5–adapted 
bivalent vaccine (and dose level).

Perform a urine pregnancy test on WOCBP as described in Section 8.3.5.

Discuss contraceptive use as described in Section 5.3.1.

Measure the participant’s height and weight.

Perform a clinical assessment.  If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination (refer to Section 8.3.1), and record any findings in the source documents 
and, if clinically significant, record any findings on the medical history CRF.

Record nonstudy vaccinations as described in Section 6.9.

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met.

On the day of and before vaccination, measure the participant’s body temperature.
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
Ensure that the participant meets none of the temporary delay criteria as described in 
Section 5.5.

On the day of and before vaccination, obtain a nasal (midturbinate) swab (collected by 
site staff).

On the day of and before vaccination, collect a blood sample (approximately 50 mL for 
participants ≥18 years of age and approximately 10 mL for participants 12 through 
17 years of age) for testing of immunogenicity and N-binding antibody.

If the participant is part of the group for description of cell-mediated immune response 
(select sites only; Cohort 2 and ≥18 years of age only; additional consent required), 
collect a blood sample (approximately 130 mL) for PBMC isolation and a further blood 
sample (approximately 5 mL) for HLA typing.

Site staff will obtain the participant’s randomization number using the IRT system and 
will receive the randomization confirmation report. 

Site staff member(s) assigned to the “unblinded” role, per the delegation log, will obtain 
the vaccine vial allocation using the IRT. The vaccination visit confirmation report with 
the study intervention allocation will only be sent to site staff members in the 
“unblinded” role.

Unblinded site staff member(s) will dispense/administer 1 dose of study intervention into 
the deltoid muscle, preferably of the nondominant arm.  Please refer to the IPM for 
further instruction on this process.

Blinded site staff must observe the participant for at least 30 minutes after study 
intervention administration for any acute reactions.  Record any acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of the 
CRF, and on an SAE form as applicable.

Record AEs as described in Section 8.4.

Explain the e-diary technologies available for this study (see Section 8.3.4) and assist the 
participant or participant’s parent(s)/legal guardian in downloading the study application 
onto the participant’s or participant’s parent(s)/legal guardian’s own device or issue a 
provisioned device if required.  

Provide instructions on e-diary completion and ask the participant or participant’s 
parent(s)/legal guardian to complete the reactogenicity e-diary from Day 1 through Day 
7, with Day 1 being the day of vaccination (see Section 8.3.4.1 through Section 8.3.4.5).

Provide a measuring device to measure local reactions at the injection site and a 
thermometer for recording daily temperatures and provide instructions on their use.
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
Ask the participant or participant’s parent(s)/legal guardian to contact the site staff or 
investigator immediately if he or she experiences any of the following from Day 1 
through Day 7 after vaccination (where Day 1 is the day of vaccination) to determine if 
an unscheduled reactogenicity visit is required:

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring greater than 10 cm 
(>20 measuring device units).

Severe pain at the injection site.

Any severe systemic event.

Ask the participant or participant’s parent(s)/legal guardian to contact the site staff or 
investigator if a medically attended event (eg, doctor’s visit, emergency room visit) or 
hospitalization occurs.

Provide instructions on COVID-19 illness e-diary completion and ask the participant or 
participant’s parent(s)/legal guardian to complete the COVID-19 illness e-diary if the 
participant is diagnosed with COVID-19 or has possible new or increased symptoms, and 
when he/she receives a reminder, at least weekly. See Section 8.10.7 for further details.
Provide instructions for use of the provided thermometer to monitor for fever (for 
COVID-19 surveillance).

Provide a self-swab kit in case of COVID-19 symptoms and provide instructions on 
self-collection of nasal swabs or instruct the participant’s parent(s)/legal guardian on the 
technique for collecting a nasal swab from their child at home.

Ask the participant or participant’s parent(s)/legal guardian to contact the site staff or 
investigator immediately if the participant experiences acute chest pain, shortness of 
breath, or palpitations (see Section 8.10.11).

Schedule an appointment for the participant to return for the next study visit.

Remind the participant or participant’s parent(s)/legal guardian to bring the e-diary
device to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the study intervention accountability records.
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
The investigator or appropriately qualified designee reviews the reactogenicity e-diary 
data online following vaccination to evaluate participant compliance and as part of the 
ongoing safety review.  Daily review is optimal during the active diary period.
8.10.2. Visit 2 – 1-Week Follow-Up Visit (6 to 8 Days After Visit 1)

Perform a clinical assessment.  If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination, per Section 8.3.1, and record any findings in the source documents and, if 
clinically significant, record any findings on the AE CRF.

Record nonstudy vaccinations as described in Section 6.9.

Record details of any of the prohibited medications specified in Section 6.9.1 received by 
the participant if required for his or her clinical care.

Record AEs as described in Section 8.4.

Discuss contraceptive use as described in Section 5.3.1.

Collect a blood sample (approximately 20 mL for participants ≥18 years of age and 
approximately 10 mL for participants 12 through 17 years of age) for immunogenicity 
testing.

If the participant is part of the group for description of cell-mediated immune response 
(select sites only; Cohort 2 and ≥18 years of age only), collect a blood sample 
(approximately 130 mL) for PBMC isolation.

Review the participant’s reactogenicity e-diary data. Collect stop dates of any 
reactogenicity e-diary events ongoing on the last day the reactogenicity e-diary was 
completed.

If the 7-day reactogenicity period is ongoing: Remind the participant or participant’s 
parent(s)/legal guardian 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.
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
Any severe systemic event.

Remind the participant or participant’s parent(s)/legal guardian 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 or participant’s parent(s)/legal guardian to contact the site staff or 
investigator (this could be via the COVID-19 illness e-diary) immediately if the 
participant experiences any symptoms as detailed in Section 8.10.7.

Ensure the participant has a self-swab kit in case of COVID-19 symptoms and provide 
instructions on self-collection of nasal swabs or instruct the participant’s parent(s)/legal 
guardian on the technique for collecting a nasal swab from their child at home. 

Ask the participant or participant’s parent(s)/legal guardian to contact the site staff or 
investigator immediately if the participant experiences acute chest pain, shortness of 
breath, or palpitations (see Section 8.10.11).

Schedule an appointment for the participant to return for the next study visit.

If the 7-day reactogenicity period is ongoing: Remind the participant or participant’s 
parent(s)/legal guardian to bring the e-diary to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.

The investigator or appropriately qualified designee reviews the reactogenicity e-diary 
data online following vaccination to evaluate participant compliance and as part of the 
ongoing safety review.  Daily review is optimal during the active diary period.
8.10.3. Visit 3 – 1-Month Follow-Up Visit (28 to 35 Days After Visit 1)

Perform a clinical assessment.  If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination, per Section 8.3.1, and record any findings in the source documents and, if 
clinically significant, record any findings on the AE CRF.

Record nonstudy vaccinations as described in Section 6.9.

Record details of any of the prohibited medications specified in Section 6.9.1 received by 
the participant if required for his or her clinical care.

Record AEs as described in Section 8.4.

Confirm contraceptive use as described in Section 5.3.1.
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
Collect a blood sample (approximately 50 mL for participants ≥18 years of age and 
approximately 10 mL for participants 12 through 17 years of age) for immunogenicity 
testing.

If the participant is part of the group for description of cell-mediated immune response 
(select sites only; Cohort 2 and ≥18 years of age only), collect a blood sample 
(approximately 130 mL) for PBMC isolation.

Review the participant’s reactogenicity e-diary data. Collect stop dates of any 
reactogenicity e-diary events ongoing on the last day the reactogenicity e-diary was 
completed and record stop dates in the CRF, if required.

Remind the participant or participant’s parent(s)/legal guardian to contact the site staff or 
investigator if a medically attended event (eg, doctor’s visit, emergency room visit) or 
hospitalization occurs.

From Cohort 4 onwards: Ask the participant or his/her parent(s)/legal guardian to contact 
the site staff or investigator immediately if the participant experiences acute chest pain, 
shortness of breath, or palpitations (see Section 8.10.11).

Ask the participant or participant’s parent(s)/legal guardian to contact the site staff or 
investigator (this could be via the COVID-19 illness e-diary) immediately if the 
participant experiences any symptoms as detailed in Section 8.10.7.

Ensure the participant has a self-swab kit in case of COVID-19 symptoms and provide 
instructions on self-collection of nasal swabs or instruct the participant’s parent(s)/legal 
guardian on the technique for collecting a nasal swab from their child at home. 

Schedule an appointment for the participant to return for the next study visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.10.4. Visit 4 – 3-Month Follow-Up Visit (84 to 98 Days After Visit 1)

Perform a clinical assessment.  If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination, per Section 8.3.1, and record any findings in the source documents and, if 
clinically significant, record any findings on the AE CRF.

Record nonstudy vaccinations as described in Section 6.9.

Record details of any of the prohibited medications specified in Section 6.9.1 received by 
the participant if required for his or her clinical care.
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
Record AEs as described in Section 8.4.

Collect a blood sample (approximately 20 mL for participants ≥18 years of age and 
approximately 10 mL for participants 12 through 17 years of age) for immunogenicity 
testing, unless advised otherwise by Pfizer.

If the participant is part of the group for description of cell-mediated immune response 
(select sites only; Cohort 2 and ≥18 years of age only), collect a blood sample 
(approximately 130 mL) for PBMC isolation.

Remind the participant or participant’s parent(s)/legal guardian 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 or participant’s parent(s)/legal guardian to contact the site staff or 
investigator (this could be via the COVID-19 illness e-diary) immediately if the 
participant experiences any symptoms as detailed in Section 8.10.7.

Ensure the participant has a self-swab kit in case of COVID-19 symptoms and provide 
instructions on self-collection of nasal swabs or instruct the participant’s parent(s)/legal 
guardian on the technique for collecting a nasal swab from their child at home. 

Schedule an appointment for the participant to return for the next study visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.10.5. Visit 5 – 6-Month Follow-Up Visit (175 to 189 Days After Visit 1)

Perform a clinical assessment.  If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination, per Section 8.3.1, and record any findings in the source documents and, if 
clinically significant, record any findings on the AE CRF.

Record nonstudy vaccinations as described in Section 6.9.

Record details of any of the prohibited medications specified in Section 6.9.1 received by 
the participant if required for his or her clinical care.

Record AEs as described in Section 8.4.

Collect a blood sample (approximately 20 mL for participants ≥18 years of age and 
approximately 10 mL for participants 12 through 17 years of age) for immunogenicity 
testing, unless advised otherwise by Pfizer.
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
If the participant is part of the group for description of cell-mediated immune response 
(select sites only; Cohort 2 and ≥18 years of age only), collect a blood sample 
(approximately 130 mL) for PBMC isolation.

Collect the participant’s e-diary provisioned device or assist the participant or 
participant’s parent(s)/legal guardian to remove the study application from his or her own 
personal device.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.10.6. 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 the criteria for Grade 4.  
A site visit must be scheduled as soon as possible to assess the participant unless any of the 
following is true:

The participant is unable to attend the unscheduled visit.

The local reaction/systemic event is no longer present at the time of the telephone 
contact.

The participant or participant’s parent(s)/legal guardian 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 that it was not needed, any ongoing local reactions/systemic events must be 
assessed at the next study visit.
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8.10.7. COVID-19 and MIS-C Surveillance
If a participant experiences any of the following (irrespective of perceived etiology or 
clinical significance), he or she is instructed to contact the site immediately and, if 
confirmed, participate in an in-person or telehealth visit as soon as possible, optimally within 
3 days of symptom onset (and at the latest 4 days after symptom resolution).

A diagnosis of COVID-19;

Fever;

New or increased cough;

New or increased shortness of breath;

Chills;

New or increased muscle pain;

New loss of taste/smell;

Sore throat;

Diarrhea;

Vomiting. 
Note that:

The CDC list of COVID-19 symptoms can be found at: 
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.42  The 
additional symptoms listed by the CDC (ie, those not listed in the above protocol-defined 
list) should not trigger a potential COVID-19 illness visit unless, in the opinion of the PI, 
it is deemed necessary.

If new symptoms are reported within 4 days after resolution of all previous symptoms, 
they will be considered as part of a single illness and a second illness visit is not required.

Surveillance of potential COVID-19 symptoms should continue even if a participant has 
a positive SARS-CoV-2 test earlier in the study. 
During the 7 days following each vaccination, potential COVID-19 symptoms that overlap 
with specific systemic events (ie, fever, chills, new or increased muscle pain, diarrhea, 
vomiting) should not trigger a potential COVID-19 illness visit unless, in the investigator’s 
opinion, the clinical picture is more indicative of a possible COVID-19 illness than vaccine 
reactogenicity. If, in the investigator’s opinion, the symptoms are considered more likely to 
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be vaccine reactogenicity, but a participant is required to demonstrate that he or she is 
SARS-CoV-2–negative, a local SARS-CoV-2 test may be performed: if positive, the 
symptoms should be recorded as a potential COVID-19 illness; if not, the symptoms that 
overlap with systemic reactogenicity events should be recorded in the reactogenicity e-diary 
or as AEs if not captured in the reactogenicity e-diary.
The participant or their parent(s)/legal guardian(s) are also instructed to contact the site 
immediately should the participant receive a positive SARS-CoV-2 test (NAAT or rapid 
antigen) result that is not accompanied by any symptoms. A potential COVID-19 visit is not 
required in this instance, but details of the positive test should be recorded in the designated 
CRF.
Participants may utilize a COVID-19 illness e-diary through an application (see 
Section 8.10.2) installed on a provisioned device or on the participant’s or participant’s 
parent(s)/legal guardian’s own personal device to prompt him/her to report a diagnosis of 
COVID-19 or any symptoms of COVID-19. Note that this does not substitute for a 
participant’s routine medical care. Therefore, participants should be encouraged to seek care, 
if appropriate, from their usual provider.
8.10.8. Potential COVID-19 Illness Visit (Optimally Within 3 Days After Potential 
COVID-19 Illness Onset)
This visit may be conducted as an in-person or telehealth visit; a telehealth visit involves the 
sharing of healthcare information and services via telecommunication technologies 
(eg, audio, video, video-conferencing software) remotely, thus allowing the participant, the 
participant’s parent(s)/legal guardian, and investigator to communicate on aspects of clinical 
care. 
As a participant’s COVID-19 illness may evolve over time, several contacts may be required 
to obtain the following information:

Record details of any of the prohibited medications specified in Section 6.9.1 received by 
the participant if required for his or her clinical care.

Record AEs as described in Section 8.4. Note: Potential COVID-19 illnesses should not 
be recorded as AEs, with the exception of those assessed by the investigator as related to 
study intervention or those meeting the criteria for SAEs.

If the visit is conducted in person, obtain a nasal (midturbinate) swab (collected by site 
staff). Alternatively, if conducted by telehealth, instruct the participant to self-collect a 
nasal (midturbinate) swab or instruct the participant’s parent(s)/legal guardian to collect a 
nasal swab from their child at home and ship for assessment at the central laboratory. 
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
If the visit is conducted in person, obtain a blood sample (approximately 20 mL for 
participants ≥18 years of age and approximately 10 mL for participants 12 through 
17 years of age), unless advised otherwise by Pfizer.

Collect COVID-19–related standard-of-care clinical and laboratory information. 
This includes, but is not limited to:

Symptoms and signs, including

Clinical signs at rest indicative of severe systemic illness (RR ≥30 breaths per 
minute, HR ≥125 beats per minute, SpO2 ≤93% on room air at sea level, or 
PaO2/FiO2 300 mm Hg).

Evidence of shock (SBP 90 mm Hg, DBP 60 mm Hg or requiring 
vasopressors).

Significant acute renal, hepatic, or neurologic dysfunction.

Respiratory failure (defined as needing high-flow oxygen, noninvasive 
ventilation, mechanical ventilation, or ECMO).

Clinical diagnosis.

Any prescribed medication to treat or intended to treat COVID-19/MIS-C illness.  
Refer to Section 6.9.

Local laboratory SARS-CoV-2 test result(s). Note that if it is routine practice to 
perform a repeat local SARS-CoV-2 test for any reason, then a repeat nasal 
(midturbinate) swab should also be obtained and shipped for assessment at the central 
laboratory.

Full blood count.

Blood chemistry, specifically creatinine, urea, LFTs, and CRP.

Imaging results (eg, CT or MRI scan) to document neurologic dysfunction.

Number and type of any healthcare contact; duration of hospitalization and ICU stay.

Death.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
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8.10.9. Potential COVID-19 Convalescent Visit (28 to 35 Days After Potential 
COVID-19 Illness Visit)
This visit is to be completed 28 to 35 days after all potential COVID-19 illness visits. A 
separate blood sample is needed for this visit for testing purposes even if it coincides with 
another visit.  No convalescent visits should be conducted after Visit 5 (6-month follow-up 
visit).

Collect/update COVID-19–related clinical and laboratory information (detailed in
Section 8.10.8).

Record details of any of the prohibited medications specified in Section 6.9.1 received by 
the participant if required for his or her clinical care.

Record AEs as described in Section 8.4. Note: Potential COVID-19 illnesses should not 
be recorded as AEs, with the exception of those assessed by the investigator as related to 
study intervention or those meeting the criteria for SAEs.

Collect a blood sample (approximately 20 mL for participants ≥18 years of age and 
approximately 10 mL for participants 12 through 17 years of age), unless advised 
otherwise by Pfizer.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.10.10. SARS-CoV-2 NAAT Results
Nasal (midturbinate) swabs for SARS-CoV-2 NAAT are obtained at:

Visit 1: Contributes to the determination of a participant’s baseline SARS-CoV-2 
infection status.

Potential COVID-19 illness visits: To determine whether symptoms experienced by the 
participant fulfill the COVID-19 case definition.
Through protocol amendment 2: Research laboratory–generated results from the illness visit 
swabs will be provided to the site once available, but this will not be in real time and cannot 
be relied upon to direct clinical care. Other research laboratory–generated results, including 
any positive vaccination visit swabs, will be provided to the site at the end of the study.
From protocol amendment 4: Research laboratory–generated results from the vaccination 
visit and illness visit swabs will be provided to the site at the end of the study only.
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Therefore, the participant or participant’s parent(s)/legal guardian should be directed to seek 
additional testing through the participant’s primary healthcare provider at a licensed clinical 
laboratory when exhibiting potential COVID-19 symptoms or otherwise receiving a positive 
result and counseled on whether to take any precautionary measures pending confirmatory 
testing, as per local guidance.
8.10.11. Additional Procedures for Monitoring of Potential Myocarditis or Pericarditis
Any study participant who reports acute chest pain, shortness of breath, palpitations, or any 
other symptom(s) that might be indicative of myocarditis or pericarditis 

Prior to Cohort 4: within 4 weeks after the study vaccination should be specifically 
evaluated, preferably by a cardiologist, for possible myocarditis or pericarditis.

From Cohort 4 onwards: within 6 weeks after the study vaccination must be evaluated by 
a cardiologist for possible myocarditis or pericarditis.
In addition to a clinical evaluation, the following should be performed:

ECG and

Measurement of the troponin level
If myocarditis or pericarditis is suspected based upon the initial evaluation, the following 
should also be performed:

Cardiac echocardiogram and/or

Cardiac magnetic resonance study
Details of the symptoms reported, and results of the investigations performed, will be 
recorded in the CRF.

Prior to Cohort 4: Any diagnosis made (eg, myocarditis, pericarditis, or other) should be 
recorded as an AE. Refer also to Section 8.4.8.

From Cohort 4 onwards: Any diagnosis of myocarditis or pericarditis is considered an 
important medical event and must be reported as an SAE (refer to Section 8.4.1.1). Other 
diagnoses should be recorded as AEs or SAEs, as appropriate. Refer to Section 8.4.3 for 
information regarding follow-up of AEs and SAEs. Refer also to Section 8.4.8.
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8.10.12. Communication and Use of Technology
In a study of this nature that requires illness events to be reported outside of scheduled study 
visits, it is vital that communication between the study site and the participant or his/her 
parent(s)/legal guardian, as appropriate, is maintained to ensure that endpoint events are not 
missed.  This study will employ various methods, tailored to the individual participant, to 
ensure that communication is maintained, and study information can be transmitted securely.  
Using appropriate technology, such as a study application, a communication pathway 
between the participant or his/her parent(s)/legal guardian, as appropriate, and the study site 
staff will be established.  The participant or his/her parent(s)/legal guardian, as appropriate, 
may be able to utilize his or her own devices to access this technology, or use a device 
provided by the sponsor.  Traditional methods of telephone communication will also be 
available.  The technology solution may facilitate the following:

A platform for recording local reactions and systemic events (reactogenicity e-diary); see 
Section 8.3.4.

Contact with the investigator, including the ability of the participant or his/her 
parent(s)/legal guardian, as appropriate, to report whether or not the participant has 
experienced symptoms that could represent a potential COVID-19 illness (COVID-19 
illness e-diary).

If a participant or his/her parent(s)/legal guardian, as appropriate, is not actively 
completing the COVID-19 illness e-diary, the investigator or designee is required to 
contact the participant or his/her parent(s)/legal guardian, as appropriate, to ascertain why 
and also to obtain details of any missed events.

Messages of thanks and encouragement from the study team.
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 Pfizer. 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 Hypothesis
Cohort 1, Cohort 2, and Cohort 4: For objectives evaluated separately within Cohort 1, 
Cohort 2, and Cohort 4, there is no formal hypothesis testing. All statistical analyses will be 
descriptive.
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Cohort 2 + Cohort 3 combined:
Superiority and Noninferiority of Anti-Omicron Immune Responses
For the >55-year age group (Cohort 2/Group 4 + Cohort 3/Group 2 combined):
The primary immunogenicity objective is to assess the superiority with respect to level of 
neutralizing titer and noninferiority with respect to seroresponse rate of the anti-Omicron 
BA.4/BA.5 immune response induced by BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg 
in the >55-year age group relative to the anti-Omicron immune response elicited by 
BNT162b2 30 µg in the >55-year age group from C4591031 Substudy E. The primary 
objective will be evaluated by the following 2 hypotheses:

The first null hypothesis (H0) is
H0: ln() – ln() ≤ln(1) vs H1: ln() – ln() > ln(1)
where ln(1) corresponds to a 1-fold margin for superiority and 
o
Ln() is the natural log of the geometric mean of SARS-CoV-2 Omicron 
(sublineage BA.4/BA.5)–neutralizing titer measured at 1 month after 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg in the >55-year age group 
(Cohort 2/Group 4 + Cohort 3/Group 2);
o
Ln() is the natural log of the geometric mean of SARS-CoV-2 Omicron 
(sublineage BA.4/BA.5)–neutralizing titer measured at 1 month after BNT162b2 
in the >55-year age group from C4591031 Substudy E.

The second null hypothesis (H0) is
H0:  − ≤−0.05 vs  H1:  − > −0.05
where -5% is the noninferiority margin for seroresponse and 
o
 Is the percentage of participants with seroresponse to the Omicron strain 
(sublineage BA.4/BA.5) at 1 month after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg in the >55-year age group (Cohort 2/Group 4 + 
Cohort 3/Group 2);
o
 Is the percentage of participants with seroresponse to the Omicron strain 
(sublineage BA.4/BA.5) at 1 month after BNT162b2 in the >55-year age group
from C4591031 Substudy E.
Seroresponse is defined as achieving a ≥4-fold rise from the baseline (before the study 
vaccination). If the baseline measurement is below the LLOQ, the postvaccination measure 
of ≥4 × LLOQ is considered seroresponse.
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Superiority based on GMR will be declared if the lower limit of the 2-sided 95% CI for the 
GMR is greater than 1; noninferiority based on seroresponse will be declared if the lower 
limit of the 2-sided 95% CI for the difference in percentages of participants with 
seroresponse is >-5%.
For the 18- through 55-year age group (Cohort 2/Group 2 + Cohort 3/Group 1 combined):
The primary immunogenicity objective is to assess the noninferiority with respect to level of 
neutralizing titer and seroresponse rate of the anti-Omicron BA.4/BA.5 immune response 
induced by BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg in the 18- through 55-year age 
group (Cohort 2/Group 2 + Cohort 3/Group 1) relative to the anti-Omicron immune response 
elicited by BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg in the >55-year age group
(Cohort 2/Group 4 + Cohort 3/Group 2). The primary objective will be evaluated by the 
following 2 hypotheses:

The first null hypothesis (H0) is
H0: ln() – ln() ≤ln(0.67) vs H1: ln() – ln() > ln(0.67)
where ln(0.67) corresponds to a 1.5-fold margin for noninferiority and 
o
Ln() is the natural log of the geometric mean of SARS-CoV-2 Omicron 
(sublineage BA.4/BA.5)–neutralizing titer measured at 1 month after 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg in the 18- through 55-year age 
group (Cohort 2/Group 2 + Cohort 3/Group 1);
o
Ln() is the natural log of the geometric mean of SARS-CoV-2 Omicron 
(sublineage BA.4/BA.5)–neutralizing titer measured at 1 month after 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg in the >55-year age group 
(Cohort 2/Group 4 + Cohort 3/Group 2).

The second null hypothesis (H0) is
H0:  − ≤−0.1 vs  H1:  − > −0.1
where -10% is the noninferiority margin for seroresponse and 
o
 Is the percentage of participants with seroresponse to the Omicron strain 
(sublineage BA.4/BA.5) at 1 month after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg in 18- through 55-year age group 
(Cohort 2/Group 2 + Cohort 3/Group 1)
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o
 Is the percentage of participants with seroresponse to the Omicron strain 
(sublineage BA.4/BA.5) at 1 month after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg in the >55-year age group 
(Cohort 2/Group 4 + Cohort 3/Group 2).
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. 
Noninferiority based on GMR will be declared if the lower limit of the 2-sided 95% CI for 
the GMR is greater than 0.67; noninferiority based on seroresponse will be declared if the 
lower limit of the 2-sided 95% CI for the difference in percentages of participants with 
seroresponse is >-10%.
Noninferiority of Anti–Reference-Strain Immune Responses
The secondary immunogenicity objective is to assess the noninferiority of the 
anti–reference-strain immune response induced by BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg in the >55-year age group relative to the anti–reference-strain 
immune response elicited by BNT162b2 30 µg in the >55-year age groups. The 
noninferiority objective will be evaluated by the following hypothesis:

The null hypothesis (H0) is
H0: ln() – ln() ≤ln(0.67) vs H1: ln() – ln() > ln(0.67)
where ln(0.67) corresponds to a 1.5-fold margin for noninferiority and 
o
Ln() is the natural log of the geometric mean of SARS-CoV-2 reference-strain–
neutralizing titers measured at 1 month after BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg in the >55-year age group 
(Cohort 2/Group 4 + Cohort 3/Group 2);
o
Ln() is the natural log of the geometric mean of SARS-CoV-2 reference-strain–
neutralizing titers measured at 1 month after BNT162b2 in the >55-year age 
group from C4591031 Substudy E.
Noninferiority based on the GMR will be declared if the lower limit of the 2-sided 95% CI 
for the GMR is greater than 0.67 (1.5-fold criterion) and the point estimate of the GMR is 
≥0.8.
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9.1.1. Estimands
The estimands corresponding to the primary objectives are described in the table in 
Section 3.
The primary safety 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 missing 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 objectives 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
Cohort 1, Cohort 2, and Cohort 4: No multiplicity adjustment is needed for objectives 
evaluated separately within Cohort 1, Cohort 2, and Cohort 4 as there are no statistical 
hypotheses.
Cohort 2 + Cohort 3 combined:
The primary and secondary objectives will be evaluated sequentially using a 1-sided alpha of 
0.025. The primary objective for the >55-year age group will be evaluated first, followed by 
the secondary objective of the GMR for >55-year age group, and then the primary objective 
for the 18- through 55-year age group. The later objective will be evaluated only if the 
previous objective is met.
The primary objectives involve 2 hypotheses: GMR and seroresponse rate difference. Both 
hypotheses within the objective must be established before evaluating the next objective in 
the sequence. Therefore, the overall type I error is fully controlled. 
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9.2. Analysis Sets
For the purpose of analysis, the following analysis sets are defined:
Population
Description
Screened
All participants who have a signed ICD.
Randomized/assigned
All participants who are assigned a randomization number in the 
IRT system.
Evaluable 
immunogenicity
All eligible randomized/assigned participants who receive the 
study intervention to which they are randomized/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 (mITT)
All randomized/assigned participants who receive the study 
intervention with a valid and determinate immunogenicity result 
after vaccination.
Safety
All participants who receive the study intervention.
9.3. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary, secondary, and 
exploratory endpoints.
9.3.1. General Considerations
CIs for all endpoints in the statistical analysis will be presented as 2-sided at the 95% level 
unless specified otherwise.
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.
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9.3.1.1. Analyses for Binary Data
Descriptive statistics for categorical variables (eg, proportions) are the percentage (%), the 
numerator (n) and the denominator (N) used in the percentage calculation, and the 95% CIs 
where applicable.
The exact 95% CI for binary endpoints for each group will be computed using the 
F distribution (Clopper-Pearson). The 95% CI for the between-group difference for binary 
endpoints will be calculated using the Miettinen and Nurminen method.
The primary approach to calculate the difference in seroresponse rate between 2 vaccine 
groups and the associated 95% CI will be based on the Miettinen and Nurminen method 
stratified by baseline neutralizing titer category (< median, ≥median).
9.3.1.2. Analyses for Continuous Data
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
standard deviation, minimum, and maximum.
9.3.1.3. Geometric Means
The geometric means will be calculated as the mean of the assay results after making the 
logarithm transformation and then exponentiating the mean to express results on the original 
scale. Two-sided 95% CIs will be obtained by taking log transforms of assay results, 
calculating the 95% CI with reference to Student’s t distribution, and then exponentiating the 
confidence limits.
Model-Based GMR:
As the primary approach, 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 neutralizing titer 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 Student’s t distribution for the mean difference of the logarithmically transformed 
assay results and exponentiating the confidence limits.
9.3.1.4. 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 
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2-sided 95% CIs will be obtained by constructing CIs using Student’s t distribution for the 
mean difference on the logarithm scale and exponentiating the confidence limits.
9.3.1.5. Reverse Cumulative Distribution Curves
Empirical RCDCs will plot proportions of participants with values equal to or exceeding a 
specified assay value versus the indicated assay value, for all observed assay values. Data 
points will be joined by a step function with data points on the left side of the step.
9.3.2. Primary Endpoints/Estimands Analysis
Endpoint
Statistical Analysis Methods
Safety
Cohort 1 and Cohort 4:

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 the study 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 within 1 month and SAEs within 6 months after study 
vaccination will be provided for each vaccine group.
Cohort 2 and Cohort 2 + Cohort 3 combined (30 µg given as a second 
booster dose to BNT162b2-experienced participants 18 through 55 and 
>55 years of age):

Reactogenicity, AEs, and SAEs will be summarized for each age 
group and vaccine dose-level group in the same way as described 
above for Cohort 1. 
Immunogenicity
For each primary immunogenicity estimand described in Section 9.3.1,
Cohort 1: At baseline and 1 month after the study vaccination:

GMTs and 2-sided 95% CIs will be provided for each vaccine group 
at each time point for SARS-CoV-2 Omicron (sublineages BA.1 and 
BA.2)–neutralizing and reference-strain–neutralizing titers.  GMTs 
will be summarized in participants without evidence of 
SARS-CoV-2 infection and in participants with and without 
evidence of SARS-CoV-2 infection.  Statistical methods are 
described in Section 9.3.1.3.
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Endpoint
Statistical Analysis Methods

GMFRs of SARS-CoV-2 Omicron (sublineages BA.1 and BA.2)–
neutralizing and reference-strain–neutralizing titers from baseline 
(before the study vaccination) to 1 month after the study 
vaccination, along with the associated 2-sided 95% CIs, will be 
provided for each vaccine group.  GMFRs will be summarized in
participants without evidence of SARS-CoV-2 infection and in 
participants with and without evidence of SARS-CoV-2 infection.  
Statistical methods are described in Section 9.3.1.4.

The percentages of participants with seroresponse to Omicron 
(sublineages BA.1 and BA.2) and reference strain at 1 month after 
the study vaccination and the associated Clopper-Pearson 95% CIs 
will be provided for each vaccine group.  The percentages of 
participants with seroresponse will be summarized in participants 
without evidence of SARS-CoV-2 infection and in participants with 
and without evidence of SARS-CoV-2 infection.

GMTs, GMFRs, and percentages of participants with seroresponse, 
along with the associated 95% CIs, will also be summarized by 
baseline SARS-CoV-2 infection status.
Cohort 2: At baseline and 1 month after the study vaccination:

For each age group and vaccine dose-level group included in Cohort 
2 and the selected subset of participants in the BNT162b2 (WT/OMI 
BA.1) 30-µg or 60-µg group from C4591031 Substudy E 
(≥18 years of age, see Section 4.1 for details), GMTs and GMFRs of 
SARS-CoV-2 Omicron (sublineages BA.1 and BA.4/BA.5)–
neutralizing and reference-strain–neutralizing titers, and percentages 
of participants with seroresponse to SARS-CoV-2 Omicron 
(sublineages BA.1 and BA.4/BA.5) and reference strain, along with 
the associated 95% CIs, will be summarized in the same way as 
described above for Cohort 1 and Cohort 4.
Cohort 2 + Cohort 3 combined:
For each primary immunogenicity objective described in Section 3 for 
Cohort 2 + Cohort 3 combined:

GMR of SARS-CoV-2 Omicron (BA.4/BA.5)–neutralizing titer at 
1 month after the study vaccination and the associated 2-sided 95% 
CIs will be calculated using the method described in Section 9.3.1.3
in participants with and without evidence of SARS-CoV-2 infection.  
As the primary approach to calculate the GMR and CI for 
neutralizing titer, a linear regression model that includes terms for 
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Endpoint
Statistical Analysis Methods
baseline neutralizing titer and comparison group will be used to 
calculate the GMR and 95% CI, along with the model-based LS 
GMTs and associated 2-sided 95% CIs for each group.

The percentages of participants with seroresponse to the Omicron 
BA.4/BA.5 strain at 1 month after the study vaccination will be 
provided. The difference in percentages of participants with 
seroresponse and the associated 2-sided 95% CIs will be calculated 
using the Miettinen and Nurminen method (see Section 9.3.1.1) in 
participants with and without evidence of SARS-CoV-2 infection.  
The primary approach to calculate the difference in seroresponse 
rate between 2 comparison groups and the associated 95% CI will be 
Miettinen and Nurminen method stratified by baseline neutralizing 
titer category (< median, ≥ median).

For the >55-year age group (Cohort 2/Group 4 + Cohort 3/Group 2 
combined), superiority based on GMR will be established if the 
model-based lower bound of the 2-sided 95% CI for GMR is greater 
than 1.  Noninferiority based on seroresponse rate difference will be 
established if the lower bound of the 2-sided 95% CI for the 
difference in percentage is greater than -5%.

For the 18- through 55-year age group (Cohort 2/Group 2 + Cohort 
3/Group 1 combined), noninferiority based on GMR will be 
established if the model-based lower bound of the 2-sided 95% CI 
for the GMR is greater than 0.67. Noninferiority based on 
seroresponse rate difference will be established if the lower bound of 
the 2-sided 95% CI for the difference in percentage is greater 
than -10%.
Cohort 4: At baseline and 1 month after the study vaccination:

GMTs and 2-sided 95% CIs of SARS-CoV-2 Omicron (sublineages 
BA.4/BA.5)–neutralizing and reference-strain–neutralizing titers 
will be provided for each vaccine group at each time point, overall 
and by baseline SARS-CoV-2 infection status. Statistical methods 
are described in Section 9.3.1.3.

GMFRs of SARS-CoV-2 Omicron (sublineages BA.4/BA.5)–
neutralizing and reference-strain–neutralizing titers from baseline 
(before the study vaccination) to 1 month after the study 
vaccination, along with the associated 2-sided 95% CIs, will be 
provided for each vaccine group, overall and by baseline 
SARS-CoV-2 infection status. Statistical methods are described in 
Section 9.3.1.4.
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
The percentages of participants with seroresponse to Omicron 
(sublineages BA.4/BA.5) and reference strain at 1 month after the 
study vaccination and the associated Clopper-Pearson 95% CIs will 
be provided for each vaccine group, overall and by baseline 
SARS-CoV-2 infection status.
9.3.3. Secondary Endpoints
Endpoint
Statistical Analysis Methods
Immunogenicity
For the first secondary immunogenicity estimand described in Section 3
for Cohort 2 + Cohort 3 combined:

GMR of the SARS-CoV-2 reference-strain–neutralizing titer at 
1 month after the study vaccination and the associated 2-sided 95% 
CIs will be calculated using the method described in Section 9.3.1.3
in participants with and without evidence of SARS-CoV-2 infection. 
A linear regression model that includes terms for baseline 
neutralizing titer and comparison group will be used to calculate the 
GMR and 95% CI, along with the model-based LS GMTs and 
associated 2-sided 95% CIs for each comparison group.

Noninferiority will be established if the model-based lower bound of 
the 2-sided 95% CI for the GMR is greater than 0.67 and the point 
estimate of the GMR is ≥0.8.
Cohort 2/Group 2 + Cohort 3/Group 1 combined and Cohort 2/Group 4 
+ Cohort 3/Group 2 combined: At baseline and 1 month after the study 
vaccination:

GMTs of SARS-CoV-2 Omicron (sublineages BA.4/BA.5)–
neutralizing and reference-strain–neutralizing titers and 2-sided 
95% CIs will be provided for each age group at each time point. 
GMTs will be summarized in participants with and without evidence 
of SARS-CoV-2 infection. Statistical methods are described in 
Section 9.3.1.3.

GMFRs of SARS-CoV-2 Omicron (sublineages BA.4/BA.5)–
neutralizing and reference-strain–neutralizing titers from baseline 
(before the study vaccination) to 1 month after the study vaccination,
along with the associated 2-sided 95% CIs, will be provided for each 
age group. GMFRs will be summarized in participants with and 
without evidence of SARS-CoV-2 infection. Statistical methods are 
described in Section 9.3.1.4.
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
The percentages of participants with seroresponse to Omicron 
(sublineages BA.4/BA.5)– and reference-strain–neutralizing titers at 
1 month after the study vaccination and the associated 
Clopper-Pearson 95% CIs will be provided for each age group. The 
percentages of participants with seroresponse will be summarized in 
participants with and without evidence of SARS-CoV-2 infection.

GMTs, GMFRs, and percentages of participants with seroresponse, 
along with the associated 95% CIs, will also be summarized by 
baseline SARS-CoV-2 infection status.
9.3.4. Exploratory Endpoints
Endpoint
Statistical Analysis Methods
Immunogenicity
Cohort 1: At baseline and 7 days, 1 month, 3 months, and 6 months
after the study vaccination:

GMTs and GMFRs of SARS-CoV-2 Omicron (sublineages BA.1 
and BA.2)–neutralizing and reference-strain–neutralizing titers, 
and percentages of participants with seroresponse to SARS-CoV-2 
Omicron (sublineages BA.1 and BA.2) and reference strain, along 
with the associated 95% CIs, will be summarized in the same way 
as described above for the primary immunogenicity endpoints of 
Cohort 1.
Cohort 2/Group 1, Cohort 2/Group 2 + Cohort 3/Group 1 combined, 
Cohort 2/Group 4 + Cohort 3/Group 2 combined, Cohort 2/Group 3, 
and Cohort 2/Group 5: At baseline and 1 month, 3 months, and 6 
months after the study vaccination:

GMTs and GMFRs of SARS-CoV-2 Omicron (sublineages 
BA.4/BA.5)–neutralizing and reference-strain–neutralizing titers, 
and percentages of participants with seroresponse to SARS-CoV-2 
Omicron (sublineages BA.4/BA.5) and reference strain, along with 
the associated 95% CIs, will be summarized in the same way as 
described above for the primary immunogenicity endpoints of 
Cohort 1.
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Cohort 4: At baseline and 7 days, 1 month, 3 months, and 6 months
after the study vaccination:

GMTs and GMFRs of SARS-CoV-2 Omicron (sublineages 
BA.4/BA.5)–neutralizing and reference-strain–neutralizing titers, 
and percentages of participants with seroresponse to SARS-CoV-2 
Omicron (sublineages BA.4/BA.5) and reference strain, along with 
the associated 95% CIs, will be summarized in the same way as 
described above for the primary immunogenicity endpoints of 
Cohort 4.
COVID-19 cases
Cohort 1, Cohort 2 + Cohort 3 combined, and Cohort 4:

Confirmed COVID-19 cases, confirmed severe COVID-19 cases, 
and strain sequencing of the COVID-19 cases will be summarized 
for each vaccine and age group.
Immune 
response to 
SARS-CoV-2 
infection
Cohort 1, Cohort 2 + Cohort 3 combined, and Cohort 4:

SARS-CoV-2–neutralizing titers at the time of a COVID-19 illness 
visit* and at the convalescent visit will be listed. 
(*Only for in-person COVID-19 visits.)
Immune 
response to other 
emerging 
variants (under 
monitoring, of 
interest, and/or 
of concern)
Cohort 1, Cohort 2 + Cohort 3 combined, and Cohort 4:

GMTs of SARS-CoV-2 variant–neutralizing titers for other 
variants (under monitoring, of interest, and/or of concern) not 
already specified, along with the associated 2-sided 95% CIs, will 
be provided at specific time points for each vaccine group.
GMFRs from baseline (before the study vaccination) to each 
subsequent time point, and percentage of participants with 
seroresponse at each time point after vaccination, along with the 
associated 2-sided 95% CIs, may also be provided for each 
vaccine group.
Cell-mediated 
immune 
response
Cohort 2:

The cell-mediated immune response and additional humoral 
immune response parameters to the reference strain and Omicron 
variant will be summarized at each time point for the subset of 
participants with PBMC samples collected in each group.
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9.4. Interim Analyses
As C4591044 is a sponsor open-label, Phase 1/2/3 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.
No formal interim analysis will be conducted.  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 for each of
Cohort 1, Cohort 2, Cohort 2 + Cohort 3 combined, and Cohort 4:

Safety and immunogenicity data through Visit 3 (1 month after study vaccination).

Safety and immunogenicity data through Visit 5 (6 months after study 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
Cohort 1, Cohort 2, and Cohort 4: For the immunogenicity analyses conducted separately for 
Cohorts 1, 2, and 4, the sample size is not based on any formal hypothesis test. All statistical 
analyses will be descriptive.
For safety outcomes, Table 8 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 2%, with 60, 100, 200,
or 300 participants in a group, there is 70%, 87%, 98%, and >99% probability of observing at 
least 1 AE, respectively.
Table 8.
Probability of Observing at Least 1 AE by Assumed True Event Rate
Assumed True Event 
Rate of an AE
N=60
N=100
N=200
N=300
0.1%
0.06
0.10
0.18
0.26
0.3%
0.16
0.26
0.45
0.59
0.5%
0.26
0.39
0.63
0.78
0.8%
0.38
0.55
0.80
0.91
1%
0.45
0.63
0.87
0.95
2%
0.70
0.87
0.98
>0.99
3%
0.84
0.95
>0.99
>0.99
4%
0.91
0.98
>0.99
>0.99
5%
0.95
0.99
>0.99
>0.99
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Cohort 2 + Cohort 3 combined: To provide sufficient power for the immunogenicity 
hypotheses for each of the age groups, the Cohort 2 18- through 55-year age and 
>55-year age groups receiving a 30-µg dose of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 
will be combined with the corresponding age and dose groups in Cohort 3.
Superiority and Noninferiority of Anti-Omicron Immunogenicity Objective

For the >55-year age group (Cohort 2/Group 4 + Cohort 3/Group 2 combined vs 
BNT162b2 30-µg group from C4591031 Substudy E): 
Assuming a 20% nonevaluable rate, with 300 participants >55 years of age receiving 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg (100 in Cohort 2/Group 2 and 200 in 
Cohort 3/Group 2) and 300 participants >55 years of age receiving BNT162b2 30 µg 
(from C4591031 Substudy E), approximately 480 evaluable participants (240 in the 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30-µg group and 240 in the BNT162b2 30-µg 
group) will contribute to the immunogenicity evaluation. The superiority evaluation based 
on GMR and noninferiority evaluation based on seroresponse rate difference will each be 
performed at 1-sided alpha level of 0.025 as described in Section 9.1.2.
For comparisons based on GMR, common assay standard deviations at 1 month after the 
third or fourth dose in log scale is assumed to be 1.45 based on data observed in the 
C4591031 Substudy E. If the true GMR of Omicron–neutralizing titer in the 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30-µg group to the BNT162b2 30-µg group is 
1.5, then 480 evaluable participants will provide 86.4% power to declare noninferiority.
For comparisons based on seroresponse rate difference, if the seroresponse rate is 65% in the 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30-µg group and 52% in the BNT162b2 30-µg 
group, the study has 98.0% power to demonstrate noninferiority using a 5% margin.

For the 18- through 55-year age group (Cohort 2/Group 2 + Cohort 3/Group 1 combined)
vs >55-year age group (Cohort 2/Group 4 + Cohort 3/Group 2 combined): 
Assuming a 20% nonevaluable rate, with 300 participants receiving BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) 30 µg in the 18- through 55-year age group (100 in Cohort 2/Group 2 
and 200 in Cohort 3/Group 1) and 300 participants receiving BNT162b2 Bivalent (WT/OMI 
BA.4/BA.5) 30 µg in the >55-year age group (100 in Cohort 2/Group 4 and 200 in Cohort 
3/Group 2), approximately 240 evaluable participants in each age group (18- through 
55-year age group and >55-year age group) will contribute to the immunogenicity evaluation. 
The noninferiority evaluation based on GMR and seroresponse rate difference will each be 
performed at 1-sided alpha level of 0.025 as described in Section 9.1.2.
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For comparisons based on GMR, common assay standard deviations at 1 month after the 
third or fourth dose in log scale is assumed to be 1.45 based on data observed in the 
C4591031 Substudy E. If the true GMR of Omicron–neutralizing titer after BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 30 µg in the 18- through 55-year age group to the 
>55-year age group is 1, then 480 evaluable participants (240 in the 18- through 55-year age 
group and 240 in the >55-year age group) will provide 86.4% power to declare 
noninferiority. 
For comparisons based on seroresponse rate difference, if the seroresponse rate after 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg is 65% in the 18- through 55-year age 
group and 65% in the >55-year age group, the study has 63.4% power to demonstrate 
noninferiority using a 10% margin. 
Noninferiority of Anti–Reference-Strain Immunogenicity Objective
For comparisons based on GMR, common assay standard deviations at 1 month after the 
third or fourth dose in log scale is assumed to be 1.05 based on data observed in the 
C4591031 Substudy E. If the true GMR of reference-strain–neutralizing titer after 
BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg to after BNT162b2 30 µg in the >55-year 
age group is 1, then 480 evaluable participants (240 in the BNT162b2 Bivalent 
[WT/OMI BA.4/BA.5] 30-µg group and 240 in the BNT162b2 30-µg group) will provide 
98.8% power to declare noninferiority using a 1.5-fold margin. 
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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 Pfizer with sufficient, accurate financial 
information as requested to allow Pfizer 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/Assent Process 
The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participant and/or his/her parent(s)/legal guardian and 
answer all questions regarding the study. The participant and/or his/her parent(s)/legal 
guardian should be given sufficient time and opportunity to ask questions and to decide 
whether or not to participate in the trial.
When consent is obtained from a participant’s parent(s)/legal guardian, the participant’s 
assent (affirmative agreement) must be subsequently obtained when the participant has the 
capacity to provide assent, as determined by the IRB/EC.  If the investigator determines that 
a participant’s decisional capacity is so limited, they cannot reasonably be consulted, then, as 
permitted by the IRB/EC and consistent with local regulatory and legal requirements, the 
participant’s assent may be waived with source documentation of the reason assent was not 
obtained. If the study participant does not provide their own assent, the source documents 
must record why the participant did not provide assent (for example, the child is not of 
assenting age per local regulations or policies), how the investigator determined that the 
person signing the consent was the participant’s parent(s)/legal guardian, the consent signer’s 
relationship to the study participant, and that the participant’s assent was obtained or 
waived. If assent is obtained verbally, it must be documented in the source documents.
If study participants are minors who reach the age of majority or if a child reaches the age of 
assent (per local IRB/EC requirements) during the study, as recognized under local law, the 
child or adolescent must then provide the appropriate assent or consent to document their 
willingness to continue in the study. For an adolescent who reaches the age of consent, 
parental consent would no longer be valid. If the enrollment of emancipated minors is 
permitted by the IRB/EC and local law, the participant must provide documentation of legal 
status to give consent without the permission of a legally authorized representative.
Participants must be informed that their participation is voluntary. Participants and/or the 
participant’s parent(s)/legal guardian 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.
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The investigator must ensure that each participant and/or his/her parent(s)/legal guardian is 
fully informed about the nature and objectives of the study, the sharing of data related to the 
study, and possible risks associated with participation, including the risks associated with the 
processing of the participant’s personal data. 
The participant and/or his/her parent(s)/legal guardian must be informed that the participant’s
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 and/or 
his/her parent(s)/legal guardian.
The participant and/or his/her parent(s)/legal guardian must be informed that the participant’s
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 and/or his/her parent(s)/legal 
guardian is fully informed about their right to access and correct the participant’s personal 
data or their child’s personal data and to withdraw consent for the processing of the
participant’s personal data or their child’s personal data.
The source documentation must include a statement that written informed consent and as 
applicable, assent, was obtained before the participant was enrolled in the study and the date 
on which the written consent/assent was obtained. The authorized person obtaining the 
informed consent must also sign the ICD.
Participants and/or the participant’s parent(s)/legal guardian must be reconsented to the most 
current version of the IRB/EC-approved ICD(s)/assent during their participation in the study 
as required per local regulations.
A copy of the ICD(s) and assent(s) must be provided to the participant and/or his/her 
parent(s)/legal guardian.
Participants who are rescreened are required to sign a new ICD.
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.
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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.
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee
This study will use an EDMC. The EDMC is independent of the study team and includes 
only external members. The EDMC charter describes the role of the EDMC in more detail.
The EDMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter. The recommendations made by the EDMC 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.
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www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT/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.
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.
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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 form and are password protected 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.
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.
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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’s designee.
Description of the use of the computerized system is documented in the data management 
plan, which is maintained by the sponsor’s designee.
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. 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.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee if requested to do so by the responsible IRB/EC or if such termination is required 
to protect the health of study participants.
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; 
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
Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.10. Publication Policy
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 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 
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access to the relevant statistical tables, figures, and reports (in their original format) required 
to develop the publication.
10.1.11. 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.
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.
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 laboratory test 
results that meet any of the conditions below must be recorded as an AE:

Is associated with accompanying symptoms.

Requires additional diagnostic testing or medical/surgical intervention.

Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.

Exacerbation of a chronic or intermittent preexisting condition, including an 
increase in 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 1 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 1 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 via PSSA or on the Vaccine SAE Report Form to Pfizer Safety throughout 
the active collection period. These requirements are delineated for 3 types of events: 
(1) SAEs; (2) nonserious AEs; and (3) exposure to the study intervention under study 
during pregnancy or breastfeeding, and occupational exposure. 
It should be noted that PSSA or the Vaccine SAE Report Form for reporting of SAE 
information is not the same as the AE page of the CRF. When the same data are collected, 
the forms must be completed in a consistent manner. AEs should be recorded using 
concise medical terminology and the same AE term should be used on both the CRF and 
via PSSA or the Vaccine SAE Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported via PSSA or on 
the Vaccine SAE Report
Form to Pfizer Safety 
Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding 
All AEs or SAEs associated 
with EDP or EDB
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)*
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE)**
Environmental or 
occupational exposure to 
the product under study to 
a 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 AE or SAE): any pregnancy information is reported to Pfizer 
Safety via PSSA or using the Vaccine SAE Report Form and EDP Supplemental Form.
** EDB is reported to Pfizer Safety via PSSA or using the Vaccine SAE Report Form, which would 
also include details of any SAE that might be associated with the EDB. 
*** Environmental or occupational exposure: AEs or SAEs associated with occupational exposure 
are reported to Pfizer Safety via PSSA or using the Vaccine SAE Report Form. 
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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 PSSA/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.

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 1 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 PSSA or the Vaccine SAE Report Form 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, PSSA or eSAE).

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 
offline 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 offline, 
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 the preferred method 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.
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.
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.
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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 in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following: 

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
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 
1 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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Sexual Abstinence
8. 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).
10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, susceptibility 
to, and severity and progression of disease. Therefore, where local regulations and 
IRBs/ECs allow, a blood sample will be collected for DNA and/or RNA analysis.

The results of genetic analyses may be reported in the CSR or in a separate study 
summary, or may be used for internal decision making without being included in a study 
report.

The sponsor or sponsor’s designee will store the DNA and/or RNA samples in a secure 
storage space with adequate measures to protect confidentiality. 

The samples will be retained as indicated:

Samples for specified genetic analysis (see Section 8.6) will be stored for up to 
15 years or other period as per local requirements.

Samples for genetic research will be labeled with a code. The key between the code and 
the participant’s personally identifying information (eg, name, address) will be held 
securely at the study site. 
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10.6. Appendix 6: 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 for all participants 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).
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
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).
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 Pfizer.
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, total bile acids, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
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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10.7. Appendix 7: Kidney Safety Monitoring Guidelines
10.7.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury
Standard kidney safety monitoring requires assessment of baseline and postbaseline serum 
creatinine (Scr measurement to eGFR [Scr-based eGFR] or [eCrCl]). Baseline and 
postbaseline Scys makes it feasible to distinguish AKI from other causes of Scr increase. If 
Scr increase is confirmed after baseline, then reflex measurement of Scys is indicated to 
estimate the combined Scr-Scys eGFR calculation (for adults only).
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.
10.7.2. Age-Specific Kidney Function Calculation Recommendations
10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI Equations
2021 CKD-EPI
Scr Only
Scr
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
if ≤ 0.7
N/A
eGFR = 143 × (Scr/0.7)-0.241   ×  (0.9938)Age
Female
if > 0.7
N/A
eGFR = 143 × (Scr/0.7)-1.200   ×  (0.9938)Age
Male
if ≤ 0.9
N/A
eGFR = 142 × (Scr/0.9)-0.302   ×  (0.9938)Age
Male
if > 0.9
N/A
eGFR = 142 × (Scr/0.9)-1.200   ×  (0.9938)Age
2021 CKD-EPI 
Scr-Scys 
Combined
Scr
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation
Female
If ≤ 0.7
If ≤ 0.8
eGFR = 130 × (Scr/0.7)-0.219  × (Scys/0.8)-0.323  × (0.9961)Age
Female
If ≤ 0.7
If > 0.8
eGFR = 130 × (Scr/0.7)-0.219  × (Scys/0.8)-0.778  × (0.9961)Age
Female
If > 0.7
If ≤ 0.8
eGFR = 130 × (Scr/0.7)-0.544  × (Scys/0.8)-0.323  × (0.9961)Age
Female
If > 0.7
If > 0.8
eGFR = 130 × (Scr/0.7)-0.544  × (Scys/0.8)-0.778  × (0.9961)Age
Male
If ≤ 0.9
If ≤ 0.8
eGFR = 135 × (Scr/0.9)-0.144  × (Scys/0.8)-0.323  × (0.9961)Age
Male
If ≤ 0.9
If > 0.8
eGFR = 135 × (Scr/0.9)-0.144  × (Scys/0.8)-0.778  × (0.9961)Age
Male
If > 0.9
If ≤ 0.8
eGFR = 135 × (Scr/0.9)-0.544  ×  (Scys/0.8)-0.323  × (0.9961)Age
Male
If > 0.9
If > 0.8
eGFR = 135 × (Scr/0.9)-0.544  ×  (Scys/0.8)-0.778  × (0.9961)Age
Inker LA et al. N Engl J Med. 2021;385:1737-49. 
10.7.3. Adverse Event Grading for Kidney Safety Laboratory Abnormalities
AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to 
CTCAE/KDIGO criteria.
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10.8. Appendix 8: Protocol Amendment History
The protocol amendment summary of changes table for the current amendment is located 
directly before the TOC. The protocol amendment summary of changes tables for past 
amendment(s) can be found below:
Amendment 1 (27 July 2022)
Overall Rationale for the Amendment: 
Inclusion of a second cohort to describe the immune response to BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5) at 30 µg in individuals ≥12 years of age and at 60 µg in adults 
≥18 years of age.  Added corresponding objectives, estimands, and endpoints and details in 
the statistical methods sections.  Study intervention details and background information 
supporting inclusion of this cohort were added.
Inclusion of prospective capture of confirmed COVID-19 cases for both Cohorts 1 and 2 with 
active COVID-19 surveillance and convalescent visits.
Protocol Amendment Summary of Changes Table 
Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 1.1
Synopsis
Updated the text with respect to the 
addition of Cohort 2. 
To obtain data on BNT162b2 
Bivalent (WT/OMI 
BA.4/BA.5) 30 µg in 
participants 12 years of age 
and above and 60 µg in 
participants 18 years of age 
and above.
Substantial
Section 1.2
Schema
Added Cohort 2.
To obtain data on BNT162b2 
Bivalent (WT/OMI 
BA.4/BA.5). 
Substantial
Section 1.3  
Schedule of 
Activities
Added text to include PBMC and 
HLA sampling in Cohort 2. 
Added blood volume for participants 
12 through 17 years of age.
Added reminder to obtain assent for 
pediatric population.
To describe B-cell and T-cell 
responses to Omicron and 
the reference strain.
To accommodate reduced 
blood draw volume for the 
younger age group.
To reflect changed informed 
consent process for pediatric 
population of Cohort 2.
Substantial
Section 2
Introduction
Added text to provide background 
on the emergence of additional 
Omicron sublineages; added
rationale for the addition of Cohort 
2.
To obtain data on BNT162b2 
Bivalent (WT/OMI 
BA.4/BA.5). 
Substantial
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 3
Objectives, 
Endpoints, and
Estimands
Updated the text with respect to the 
addition of Cohort 2. 
To describe the analysis of 
data from Cohort 2.
Substantial
Section 4
Study Design
Updated the text with respect to the 
addition of Cohort 2. 
To obtain data on BNT162b2 
Bivalent (WT/OMI 
BA.4/BA.5).
Substantial
Section 5.1
Inclusion Criteria
Updated inclusion criteria 1, 2, 4,
and 5 with respect to the addition of 
Cohort 2.
To obtain data on BNT162b2 
Bivalent (WT/OMI 
BA.4/BA.5).
Substantial
Section 6
Study Intervention(s) 
and Concomitant 
Therapy
Updated the text with respect to the 
addition of Cohort 2. 
To obtain data on BNT162b2 
Bivalent (WT/OMI 
BA.4/BA.5). 
Substantial
Section 6.4
Blinding
Updated the text with respect to the 
addition of Cohort 2. 
To describe the change in 
blinding for Cohort 2. 
Substantial
Section 8
Study Procedures
Added text to include PBMC and 
HLA sampling in Cohort 2. Added 
text regarding the total blood 
sampling volume for participants 
providing these optional samples.
Added text regarding the total blood 
sampling volume for participants 12 
through 17 years of age.
To describe B-cell and T-cell 
responses to Omicron and 
the reference strain.
To accommodate reduced 
blood draw volume for the 
younger age group.
Substantial
Section 9.3.4
Exploratory 
Objectives
Updated the text with respect to the 
addition of Cohort 2. 
To describe the analysis of 
data from Cohort 2
Substantial
Section 10.5
Genetics
Added Section 10.5 because of the 
inclusion of PBMC sampling in 
Cohort 2.
To describe B-cell and T-cell 
responses to Omicron and 
the reference strain.
Substantial
Section 1.1
Synopsis
Updated the exploratory objectives 
and endpoints to include confirmed
COVID-19 and severe COVID-19 
cases in each vaccine and age group, 
with respect to COVID-19 
surveillance.
To describe the analysis of 
data from COVID-19 
surveillance.
Substantial
Section 1.2
Schema
Added COVID-19 Surveillance.
To describe confirmed 
COVID-19 and severe 
COVID-19 cases in each 
vaccine and age group.
Substantial
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 1.3 
Schedule of 
Activities
Added text with respect to COVID-
19 surveillance and activities related 
to potential COVID-19 illness visits 
and convalescent visits. This 
includes provision of nasal self-swab 
kits and instructions on self-
collection of nasal swabs. Included 
statement that any AEs occurring 
within 48 hours of nasal swab 
collection should be reported. 
Because of inclusion of the illness e-
diary, deletion of the e-diary 
application or collection of the 
provisioned device was moved from 
the 1-month follow-up visit to the 6-
month follow-up visit.
To describe confirmed 
COVID-19 and severe 
COVID-19 cases in each 
vaccine and age group.
Substantial
Section 3
Objectives, 
Endpoints, and 
Estimands
Updated the exploratory objectives 
and endpoints to include confirmed 
COVID-19 and severe COVID-19 
cases in each vaccine and age group, 
with respect to COVID-19 
surveillance.
To describe the analysis of 
data from COVID-19 
surveillance.
Substantial
Section 4.2
Scientific Rationale
Updated the text with respect to 
COVID-19 surveillance.
To describe confirmed 
COVID-19 and severe 
COVID-19 cases in each 
vaccine and age group.
Substantial
Section 8
Study Procedures
Updated the text with respect to 
COVID-19 surveillance and 
procedures related to potential 
COVID-19 illness visits and 
convalescent visits.
Because of inclusion of the illness e-
diary, deletion of the e-diary 
application or collection of the 
provisioned device was removed 
from the 1-week and 1-month 
follow-up visits to the 6-month 
follow-up visit.
To describe confirmed 
COVID-19 and severe 
COVID-19 cases in each 
vaccine and age group. 
Substantial
Section 8.4.8
Adverse Events of 
Special Interest
Updated to remove confirmed 
COVID-19 diagnosis as an AESI. 
To include COVID-19 illness 
visits. To capture COVID-19 
within that data set and not to 
duplicate it as an AE.
Substantial
Section 9.3.4
Exploratory 
Endpoints
Updated with respect to exploratory 
objective and endpoints for COVID-
19 surveillance.
To describe the analysis of 
data from COVID-19 
surveillance.
Substantial
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 1.3
Schedule of 
Activities
Removed allowance for Visit 1 to be 
conducted over 2 consecutive days.
To align with recruitment 
expectations and visit 
scheduling.
Nonsubstantial
Section 4.2.2
Choice of 
Contraception/Barrier 
Requirements
Updated the text with respect to the 
addition of Cohort 2. 
To clarify the requirement 
for contraception.
Nonsubstantial
Section 5.5
Temporary Delay 
Criteria
Replaced “oral temperature” with 
“body temperature.” The 
temperature measurement route is 
per investigator discretion.  
To align with Sections 1.3 
(Schedule of Activities), 
8.3.2 (Vital Signs), and 
8.10.1 (Visit 1 study 
procedures). 
Nonsubstantial
Section 6.3
Assignment to Study 
Intervention
Added day range to strata.
To clarify stratification.
Nonsubstantial
Section 8.10.1
Visit 1 – Study 
Intervention 
Administration –
Day 1
Removed the allowance for Visit 1 
to be conducted over 2 consecutive 
days.
To align with recruitment 
expectations and visit 
scheduling.
Nonsubstantial
All
Administrative corrections to 
formatting, typographical errors, and 
naming of “Pfizer,” where 
necessary.
Administrative correction.
Nonsubstantial
Section 11
References
Updated with respect to text added 
per protocol amendment 1 changes.
To record additional 
references.
Nonsubstantial
Amendment 2 (24 August 2022)
Overall Rationale for the Amendment: 
Inclusion of a third cohort to allow for a sufficiently powered evaluation of BNT162b2 
Bivalent (WT/OMI BA.4/BA.5) 30 µg as a second booster dose in BNT162b2-experienced 
participants ≥18 years of age.  Added corresponding objectives, estimands, and endpoints 
and details in the statistical methods sections.  Study intervention details and background 
information supporting inclusion of this cohort were added. 
Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Cover page
Amended the title to remove 
blinding level and to change 
from Phase 2 to Phase 2/3. 
Corrected Study Intervention 
Name to reflect ‘BNT162b’.
With addition of Cohort 3, the 
mix of blinding levels by 
cohort is detailed in 
Sections 4.1 and 6.4.
Substantial
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 4.2
Scientific Rationale for 
Study Design
Updated to include Phase 3 per 
title change.
Cohort 3 is considered a 
Phase 3 study, consistent with 
how we have described prior 
variant vaccine evaluations in 
300 participants per group.
Section 1.1
Synopsis
Updated rationale on 
prevalence of Omicron BA.4 
and BA.5 sublineages.
To reflect the evolving 
pandemic and medical need 
for prevention of Omicron 
BA.4 and BA.5 sublineages.
Substantial
Section 1.1
Synopsis
Updated text with respect to 
the addition of Cohort 3, 
including the protocol title.
To obtain additional data on 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5).
Substantial
Section 1.2
Schema
Added Cohort 3.
To obtain additional data on 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5).
Substantial
Section 1.3
Schedule of Activities 
Noted that PBMC sampling 
and HLA typing are not 
applicable for Cohort 3. 
Cohort 3 is not part of the 
PBMC subset.
Substantial
Added blood sample collection 
in the potential COVID-19 
illness visit for participants 
who have this visit in person.
To comply with regulatory 
agency requests.
Section 2
Introduction
Updated text on the prevalence 
of Omicron BA.4 and BA.5 
sublineages.
To reflect the evolving 
pandemic and medical need 
for prevention of Omicron 
BA.4 and BA.5 sublineages.
Substantial
Section 3
Objectives, Endpoints, 
and Estimands
Updated to reflect the addition 
of Cohort 3.
To obtain additional data on 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5).
Substantial
For the Cohort 2 primary 
immunogenicity objective, 
added clarification to the 
selection of comparator 
participants from C4591031 
Substudy E.
To comply with regulatory 
agency requests.
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 4.1
Overall Design
Updated to reflect the addition 
of Cohort 3.
To obtain additional data on 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5).
Substantial
For the Cohort 2 primary 
immunogenicity objective, 
added clarification to the 
selection of comparator 
participants from C4591031 
Substudy E.
To comply with regulatory 
agency requests.
Section 5.1
Inclusion Criteria
Updated to reflect the addition 
of Cohort 3.
To obtain additional data on 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5).
Substantial
Section 6
Study Interventions
Updated to reflect the addition 
of Cohort 3.
To obtain additional data on 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5).
Substantial
Section 8.1
Administrative and 
Baseline Procedures
Clarifications made to blood 
volumes and added blood 
sample for in-person potential 
COVID-19 illness visits.
To comply with regulatory 
agency requests and clarify 
volume calculations.
Substantial
Section 8.10.8
Potential 
COVID-19 Illness 
Visit
Added blood sample collection 
in the potential COVID-19 
illness visit for participants 
who have this visit in person.
To comply with regulatory 
agency requests.
Substantial
Section 9
Statistical 
Considerations
Updated to reflect the addition 
of Cohort 3 and its associated 
analyses. 
To obtain additional data on 
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5).
Substantial
Section 5.2
Exclusion Criteria
Clarifications. 
In response to site inquiries 
and for alignment with other 
C459 studies. 
Nonsubstantial
Section 6
Study Interventions 
and Concomitant 
Therapy
Added: “For the purposes of 
this protocol, study 
intervention refers to 
investigational product”
Content was added to match 
current protocol template.
Nonsubstantial
Section 6.9.1
Prohibited During the 
Study
Clarifications. 
In response to site inquiries 
and for alignment with other 
C459 studies. 
Nonsubstantial
Section 8.2.1
Surveillance for 
COVID-19
Title of section updated.
Title updated to better reflect 
objective.
Nonsubstantial
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 8.3.4.3
Systemic Events
Corrected instructions 
explaining what should occur 
in the event of a local positive 
SARS-CoV-2 test in a 
symptomatic participant.  
To align with sections 8.4.8, 
8.10.7 and 8.10.8.
Nonsubstantial
Section 8.3.4.4
Fever
Edits made to Table 7: Scale 
for Fever.
To align how Celsius 
temperature ranges were 
presented with FDA reference 
and content within section. 
Nonsubstantial
Section 8.4.5.1
Exposure During 
Pregnancy
Updated to reflect study 
definition of Exposure During 
Pregnancy as per other content 
within section.
Updated to maintain 
consistency within section.
Nonsubstantial
All
Minor editorial changes.
Corrections or minor edits in 
line with amendment updates.
Nonsubstantial
Amendment 3 (14 April 2023)
Protocol amendment 3 was created but not implemented. The next amendment (protocol 
amendment 4) was developed from protocol amendment 2. 
Amendment 4 (26 May 2023)
Overall Rationale for the Amendment: 
Inclusion of a fourth cohort to describe the immune response to authorized and new 30-µg 
bivalent and monovalent Omicron BA.4/BA.5–modified BNT162b vaccines:  

BNT162b2 Bivalent (Original/OMI BA.4/BA.5) 

BNT162b5 Bivalent (Original/OMI BA.4/BA.5) 

BNT162b7 Bivalent (Original/OMI BA.4/BA.5)

BNT162b7 Monovalent (OMI BA.4/BA.5) 
given to mRNA COVID-19 vaccine–experienced participants 18 through 55 years of age.  
Added corresponding objectives, estimands, and endpoints and details in the statistical 
methods sections.  Study intervention details and background information supporting the 
inclusion of this cohort were also added. 
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Protocol Amendment Summary of Changes Table 
Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Cover page, synopsis, 
and sections referring to 
phase of study
Added “Phase 1.”
This study is considered 
Phase 1/2 for the cohorts 
evaluating BNT162b5 
bivalent and BNT162b7 
bivalent and monovalent.  
Substantial
Cover page
Added IND number 
29525.
Per feedback from 
FDA/CBER, BNT162b7 
is considered a new 
vaccine and, as such, 
clinical studies should be 
conducted under a new 
IND.
Substantial
Protocol Summary: 
Section 1.1, Section 1.2
and Section 1.3 
Updated text, tables, and 
schema with respect to the 
addition of Cohort 4. 
To obtain data on the 
authorized and new 
30-µg bivalent and 
monovalent Omicron 
BA.4/BA.5–modified 
BNT162b vaccines in 
participants 18 through 
55 years of age.
Substantial
Section 2
Introduction
Added text to provide 
background and rationale 
for the addition of 
Cohort 4.
To obtain data on the 
new 30-µg bivalent and 
monovalent BNT162b 
vaccines.
Substantial
Section 1.1 and 
Section 3
Objectives, Endpoints, 
and Estimands
Updated the text with 
respect to the addition of 
Cohort 4. 
To describe the analysis 
of data from Cohort 4.
Substantial
Section 3
Objectives, Endpoints, 
and Estimands
Updated the primary 
immunogenicity estimands 
for Cohort 1.
To specify the analysis 
time points for the 
primary immunogenicity 
analysis and to move the 
Day 7 time point to 
exploratory objectives to 
reflect the final analysis. 
Substantial
Section 3
Objectives, Endpoints, 
and Estimands
Updated the primary 
immunogenicity estimands 
for Cohort 2.
To retain the primary 
endpoint time point in 
primary objective 
(1-month time point) and 
to move the analysis at 
the rest of the time 
points to exploratory 
objectives to reflect the 
final analysis. 
Substantial
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 3
Objectives, Endpoints, 
and Estimands
Merged the 
immunogenicity objectives 
of Cohort 2 and Cohort 3 
and select subsets of 100 
participants each from 
Cohort 2/Group 2 + 
Cohort 3/Group 1 
combined, Cohort 2/Group 
4 + Cohort 3/Group 2 
combined, and the 
C4591031 Substudy E 
expanded-cohort 
BNT162b2 30-µg group 
for the final analysis.
To combine Cohort 2 
and Cohort 3 
immunogenicity data to 
reflect the final analysis.
Substantial
Section 3
Objectives, Endpoints, 
and Estimands
Updated the 
immunogenicity estimands 
for the Cohort 2 + 
Cohort 3 combined 
analysis.
To split out the 1-month 
analysis to reflect the 
analysis performed for 
the interim CSR.
Substantial
Section 4
Study Design
Added Cohort 4–specific 
information to Sections 
4.1, 4.2, and 4.3.
Updated for the addition 
of Cohort 4.
Substantial
Section 5.1
Inclusion Criteria
Added Cohort 4–specific 
inclusion criteria.
Updated for the addition 
of Cohort 4.
Substantial
Section 6.1
Study Interventions 
Administered
Added the Cohort 4 
vaccines and study 
intervention details.
Updated for the addition 
of Cohort 4.
Substantial
Section 6.3
Assignment to Study 
Intervention
Added the Cohort 4 
randomization scheme.
Updated for the addition 
of Cohort 4.
Substantial
Section 6.4.1
Blinding of Participants 
Added text to specify the 
unblinding time point.
The unblinding time 
point was established for 
Cohorts 1 and 2 and 
anticipated for Cohort 4.  
Substantial
Section 6.4.4
Breaking the Blind
Added text to distinguish 
emergency unblinding 
procedures and 
nonemergency unblinding 
procedures (Pfizer 
unblinding time point).
The unblinding time 
point was established for 
Cohorts 1 and 2 and 
anticipated for Cohort 4.  
Substantial
Section 8.4.7
Disease-Related Events 
and/or Disease Related 
Outcomes Not 
Revised text to indicate 
that study swab results will 
now be released to 
investigators at the end of 
the study only.
Change to information 
related to release of 
study swab results. 
Change to SAE reporting 
requirements for 
Substantial
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Qualifying as AEs or 
SAEs
Section 8.10.10
SARS-CoV-2 NAAT 
Results
potential COVID-19 
illness cases in line with 
this change to the release 
of results.
Section 8.10.1
Study procedures for 
Visit 1 
Added prior COVID-19 
vaccines documentation 
for Cohort 4.
To update for the 
addition of Cohort 4.
Substantial
Section 9.3.2
Primary 
Endpoints/Estimands 
Analysis
Updated Section 9.3.2 to 
align with the changes to 
the objectives. 
Added Cohort 4.
To update to reflect the 
final analysis. 
To describe the analysis 
of data from Cohort 4.
Substantial
Section 9.3.3
Secondary Endpoints
Updated Section 9.3.3 to 
align with the changes to 
the objectives. 
To update to reflect the 
final analysis. 
Substantial
Section 9.3.4
Exploratory Endpoints
Updated Section 9.3.4 to 
align with the changes to 
the objectives.
Added Cohort 4.
To describe the analysis 
of data from Cohort 4.
Substantial
Section 9.5
Sample Size 
Determination
Added Cohort 4.
To obtain data on 
authorized and new 
30-µg bivalent and 
monovalent Omicron 
BA.4/BA.5–modified 
BNT162b vaccines.
Substantial
Section 9.4
Interim Analysis
Updated to reflect that the 
study is Phase 2/3 and 
open-label to the sponsor.
To clarify and to support 
the change made to 
Section 9.4.1 per the 
PACL dated 15 Feb 
2023.
Nonsubstantial
Section 9.4.1
Analysis Timing
Clarified that additional 
analyses may be conducted 
and analyses may be 
combined. 
To permit analyses to 
inform product 
development and/or for 
program-level decisions 
per the PACL dated 15 
Feb 2023.
Nonsubstantial
Section 10.8
Appendix 8: Protocol
Amendment History
Added Amendment 2 
summary of changes.
Protocol template 
requirement.
Nonsubstantial
Section 10.9
Appendix 9: 
Abbreviations
Updated with vaccines for
Cohort 4.
Administrative updates 
for the Cohort 4 addition 
to the protocol.
Nonsubstantial
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 11
References
Updated with respect to 
text added per protocol 
amendment 4 changes.
To record additional 
references.
Nonsubstantial
Various sections 
Made minor clarifications 
and editorial changes.
Edits to improve clarity 
and administrative 
corrections.
Nonsubstantial
Amendment 5 (23 June 2023)
Protocol amendment 5 was created but not implemented. The next amendment 
(protocol amendment 6) was developed from protocol amendment 4. 
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10.9. Appendix 9: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
AESI
adverse event of special interest
AKI
acute kidney injury
ALT
alanine aminotransferase
ARDS
acute respiratory distress syndrome
AST
aspartate aminotransferase
AxMP
auxiliary medicinal product
BCR
B-cell receptor
-hCG
-human chorionic gonadotropin
BNP
brain natriuretic peptide
BNT162b2 Bivalent 
(WT/OMI BA.1)
BNT162b2 Wild Type and BNT162b2 OMICRON 
(B.1.1.529 sublineage BA.1)
BNT162b2 Bivalent 
(Original/OMI
BA.4/BA.5)
BNT162b2 Original and BNT162b2 OMICRON 
(B.1.1.529 sublineage BA.4/BA.5)
BNT162b2 Bivalent 
(WT/OMI BA.4/BA.5)
BNT162b2 Wild Type and BNT162b2 OMICRON 
(B.1.1.529 sublineage BA.4/BA.5)
BNT162b5 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b5 Original and BNT162b5 OMICRON 
(B.1.1.529 sublineage BA.4/BA.5)
BNT162b5 Bivalent 
(WT/OMI BA.2)
BNT162b5 Wild Type and BNT162b5 OMICRON 
(B.1.1.529 sublineage BA.2)
BNT162b6 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b6 Original and BNT162b6 OMICRON 
(B.1.1.529 sublineage BA.4/BA.5)
BNT162b7 Bivalent 
(Original/OMI 
BA.4/BA.5)
BNT162b7 Original and BNT162b7 OMICRON 
(B.1.1.529 sublineage BA.4/BA.5)
BNT162b7 Monovalent 
(OMI BA.4/BA.5)
BNT162b7 OMICRON (B.1.1.529 sublineage BA.4/BA.5)
CBER
Center for Biologics Evaluation and Research (United States)
CDC
Centers for Disease Control and Prevention (United States)
CFR
Code of Federal Regulations
ChAdOx1-S
ChAdOx1-S (recombinant) SARS-CoV-2 vaccine 
(AstraZeneca)
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
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PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 166
Abbreviation
Term
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CRP
C-reactive protein
CSR
clinical study report
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CTIS
Clinical Trial Information System
CVA
cerebrovascular accident
DBP
diastolic blood pressure
DCT
data collection tool
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DRE
disease-related event
DU
dispensable unit
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram
ECMO
extracorporeal membrane oxygenation
eCrCl
estimated creatinine clearance
eCRF
electronic case report form
EDB
exposure during breastfeeding
e-diary
electronic diary
EDMC
external data monitoring committee
EDP
exposure during pregnancy
eGFR
estimated glomerular filtration rate
eSAE
electronic serious adverse event
ESR
erythrocyte sedimentation rate
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)
FIH
first-in-human
FiO2
fraction of inspired oxygen
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GI
gastrointestinal
GMFR
geometric mean fold rise
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 167
Abbreviation
Term
GMR
geometric mean ratio
GMT
geometric mean titer
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HLA
human leukocyte antigen
HR
heart rate
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use
ICU
intensive care unit
ID
identification
IgG
immunoglobulin G
IL-6
interleukin 6
IMP
investigational medicinal product
IND
investigational new drug
INR
international normalized ratio
IP
investigational product
IPAL
Investigational Product Accountability Log
IPM
investigational product manual
IRB
institutional review board
IRT
interactive response technology
KDIGO
Kidney Disease: Improving Global Outcomes
LDH
lactate dehydrogenase
LFT
liver function test
LLOQ
lower limit of quantitation
LNP
lipid nanoparticle
LS
least square
MDR
Medical Device Regulation
MedDRA
Medical Dictionary for Regulatory Activities
MIS-C
multisystem inflammatory syndrome in children
mITT
modified intent-to-treat
modRNA
nucleoside-modified messenger ribonucleic acid
MQI
medically qualified individual
MRI
magnetic resonance imaging
mRNA
messenger ribonucleic acid
mRNA-1273
mRNA-1273 SARS-CoV-2 vaccine (Moderna)
N/A
not applicable
NAAT
nucleic acid amplification test
N-binding
SARS-CoV-2 nucleoprotein–binding
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 168
Abbreviation
Term
NIMP
noninvestigational medicinal product
OMI
Omicron
P2 S
SARS-CoV-2 full-length, P2 mutant, prefusion spike 
glycoprotein
P6 S
SARS-CoV-2 full-length, P6 mutant, prefusion spike 
glycoprotein
P6’ S
SARS-CoV-2 full-length, P6 prime mutant, prefusion spike 
glycoprotein
PACL
protocol administrative change letter
PaO2
partial pressure of oxygen, arterial
PBMC
peripheral blood mononuclear cell
PI
principal investigator
PPE
personal protective equipment
PSSA
Pfizer's Serious Adverse Event Submission Assistant
PT
prothrombin time
QTL
quality tolerance limit
RBD
receptor binding domain
RCDC
reverse cumulative distribution curve
RNA
ribonucleic acid
RR
respiratory rate
RT-PCR
reverse transcription–polymerase chain reaction
S1
spike protein S1 subunit
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV
severe acute respiratory syndrome coronavirus
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SBP
systolic blood pressure
Scr
serum creatinine
Scys
serum cystatin C
SI
study intervention
SmPC
summary of product characteristics
SoA
schedule of activities
SOP
standard operating procedure
SpO2
oxygen saturation as measured by pulse oximetry
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
T bili
total bilirubin
TCR
T-cell receptor
Th1
T-helper type 1
UK
United Kingdom
ULN
upper limit of normal
US
United States
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 169
Abbreviation
Term
USPI
US prescribing information
Vax
vaccination
VE
vaccine efficacy
WOCBP
woman/women of childbearing potential
WT
wild type
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 170
11. REFERENCES
1
Viper Group COVID19 Vaccine Tracker Team. COVID19 vaccine tracker: 
Pfizer/BioNTech:Comirnaty. Available from:
https://covid19.trackvaccines.org/vaccines/6/.  Accessed: 07 Apr 2023.
2
FDA. Comirnaty and Pfizer-BioNTech COVID-19 vaccine. BLA approval letter,
23 Aug 2021. Available from: https://www. fda.gov/media/151710/download. 
Accessed: 23 May 2023.
3
FDA. Coronavirus (COVID-19) update: FDA expands eligibility for Pfizer-BioNTech 
COVID-19 booster dose to 16- and 17-year-olds [press release]. Available from: 
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-
fda-expands-eligibility-pfizer-biontech-covid-19-booster-dose-16-and-17.
Published: 09 Dec 2021. Accessed: 07 Apr 2023.
4
Pfizer. Pfizer and BioNTech receive CHMP positive opinion for COVID-19 vaccine 
booster in the European Union [press release]. Available from:  
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-
receive-chmp-positive-opinion-covid-19. Published: 04 Oct 2021. 
Accessed: 07 Apr 2023.
5
Bar-On YM, Goldberg Y, Mandel M, et al. Protection of BNT162b2 vaccine booster 
against Covid-19 in Israel. N Engl J Med. 2021;385(15):1393-400.
6
FDA. Review memorandum, 28 Mar 2022: CBER assessment of a second booster dose 
of the Pfizer-BioNTech COVID-19 vaccine (0.3 mL) administered following a first 
booster dose of any FDA authorized or approved COVID-19 vaccine in certain 
individuals. Available from: https://www.fda.gov/media/157364/download.  
Accessed 07 Apr 2023.
7
Pfizer. Pfizer and BioNTech granted FDA emergency use authorization of Omicron 
BA.4/BA.5-adapted bivalent COVID-19 vaccine booster for ages 12 years and older 
[press release]. Available from: https://www.pfizer.com/news/press-release/press-
release-detail/pfizer-and-biontech-granted-fda-emergency-use-authorization. 
Published: 31 Aug 2022. Accessed: 08 Feb 2023.
8
FDA. Coronavirus (COVID-19) update, 18 Apr 2023: FDA authorizes changes to 
simplify use of bivalent mRNA COVID-19 vaccines [press release]. Available from: 
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-
fda-authorizes-changes-simplify-use-bivalent-mrna-covid-19-vaccines.  
Published: 18 Apr 2023. Accessed 09 May 2023.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 171
9
Pfizer and BioNTech. BNT162b2 [COMIRNATY (COVID-19 vaccine, mRNA)] 
evaluation of a booster dose (third dose). Vaccines and Related Biological Products 
Advisory Committee meeting briefing document, 17 Sep 2021. Available from: 
https://www.fda.gov/media/152161/download. Accessed 07 Apr 2023.
10
Pfizer. Real-world evidence confirms high effectiveness of Pfizer-BioNTech COVID-19 
vaccine and profound public health impact of vaccination one year after pandemic 
declared [press release]. Available from: https://www.pfizer.com/news/press-
release/press-release-detail/real-world-evidence-confirms-high-effectiveness-pfizer.  
Published: 11 Mar 2021. Accessed: 07 Apr 2023.
11
WHO. Weekly epidemiological update on COVID-19 -
29 Mar 2022. Available from: https://www.who.int/publications/m/item/weekly-
epidemiological-update-on-covid-19---29-march-2022. Accessed: 07 Apr 2023.
12
WHO. Weekly epidemiological update on COVID-19 -
16 Mar 2023. Available from: https://www.who.int/publications/m/item/weekly-
epidemiological-update-on-covid-19---16-march-2023. Accessed: 20 Jul 2023.
13
Ma KC, Shirk P, Lambrou AS, et al. Genomic surveillance for SARS-CoV-2 variants:
circulation of Omicron lineages — United States, January 2022–May 2023. MMWR 
Morb Mortal Wkly Rep. 2023;72(24):651-6.
14
CDC. COVID data tracker: variant proportions Available from: 
https://covid.cdc.gov/covid-data-tracker/#variant-proportions.  Accessed: 15 Jul 2023.
15
UK Health Security Agency. SARS-CoV-2 variants of concern and variants under 
investigation in England. Available 
from:https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attach
ment_data/file/1044481/Technical-Briefing-31-Dec-2021-
Omicron_severity_update.pdf.  Published: 31 Dec 2021. Accessed: 02 May 2022.
16
Feikin DR, Higdon MM, Abu-Raddad LJ, et al. Duration of effectiveness of vaccines 
against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review 
and meta-regression [erratum appears in Lancet. 2022;04 Apr:S0140-6736(22)00428-7]. 
Lancet. 2022;399(10328):924-44.
17
Ferdinands JM, Rao S, Dixon BE, et al. Waning 2-dose and 3-dose effectiveness of 
mRNA vaccines against COVID-19-associated emergency department and urgent care 
encounters and hospitalizations among adults during periods of Delta and Omicron 
variant predominance - VISION Network, 10 states, August 2021-January 2022. 
MMWR Morb Mortal Wkly Rep. 2022;71(7):255-63.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 172
18
Andrews N, Stowe J, Kirsebom F, et al. Covid-19 vaccine effectiveness against the 
Omicron (B.1.1.529) variant. N Engl J Med. 2022;386(16):1532-46.
19
FDA. Coronavirus (COVID-19) update: FDA recommends inclusion of Omicron 
BA.4/5 component for COVID-19 vaccine booster doses [press release]. Available 
from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-
update-fda-recommends-inclusion-omicron-ba45-component-covid-19-vaccine-booster. 
Accessed: 15 Jul 2022.
20
Tenforde MW, Weber ZA, Natarajan K, et al. Early estimates of bivalent mRNA 
vaccine effectiveness in preventing COVID-19–associated emergency department or 
urgent care encounters and hospitalizations among immunocompetent adults — VISION 
Network, nine states, September–November 2022. MMWR Morb Mortal Wkly Rep.
2023;71(51-52):1616-24.
21
Surie D, DeCuir J, Zhu Y, et al. Early estimates of bivalent mRNA vaccine effectiveness 
in preventing COVID-19–associated hospitalization among immunocompetent adults 
aged ≥65 years — IVY Network, 18 states, September 8–November 30, 2022. MMWR 
Morb Mortal Wkly Rep. 2022;71(51-52):1625-30.
22
Fabiani M, Mateo-Urdiales A, Sacco C, et al. Protection against severe COVID-19 after 
second booster dose of adapted bivalent (original/Omicron BA.4-5) mRNA vaccine in 
persons ≥60 years, by time since infection, Italy, 12 September to 11 December 2022. 
Euro Surveill. 2023;28(8):2300105. 
23
Lin DY, Xu Y, Gu Y, et al. Effectiveness of bivalent boosters against severe Omicron 
infection. N Engl J Med. 2023;388(8):764-6.
24
Poukka E, Goebeler S, Nohynek H, et al. Bivalent booster effectiveness against severe 
COVID-19 outcomes in Finland, September 2022 – January 2023. medRxiv. Preprint 
posted: 05 Mar 2023. DOI:10.1101/2023.03.02.23286561.
25
CDC. COVID-19 vaccine effectiveness updates. Feb 2023. Available from: 
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2023-02/slides-02-
24/COVID-07-Britton-508.pdf. Accessed: 05 Apr 2023.
26
Cohen KW, Linderman SL, Moodie Z, et al. Longitudinal analysis shows durable and 
broad immune memory after SARS-CoV-2 infection with persisting antibody responses 
and memory B and T cells. Cell Rep Med. 2021;2(7):100354.
27
Du L, He Y, Zhou Y, et al. The spike protein of SARS-CoV--a target for vaccine and 
therapeutic development. Nat Rev Microbiol. 2009;7(3):226-36. 
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 173
28
Nemet I, Kliker L, Lustig Y, et al. Third BNT162b2 vaccination neutralization of 
SARS-CoV-2 Omicron infection. N Engl J Med. 2022;386(5):492-4.
29
Hachmann NP, Miller J, Collier AY, et al. Neutralization escape by SARS-CoV-2 
Omicron subvariants BA.2.12.1, BA.4, and BA.5. N Engl J Med. 2022;387(1):8-88.
30
Tegally H, Moir M, Everatt J, et al. Emergence of SARS-CoV-2 Omicron lineages 
BA.4 and BA.5 in South Africa. Nat Med. 2022. Available from: 
https://doi.org/10.1038/s41591-022-01911-2. Accessed: 08 Jul 2022.
31
Wang X, Jiang S, Jiang S, et al. Neutralization of SARS-CoV-2 BQ.1.1 and XBB.1.5 
by breakthrough infection sera from previous and current waves in China. bioRxiv. 
Preprint posted: 18 Feb 2023. DOI:10.1101/2023.02.07.527406.
32
Yue C, Song W, Wang L, et al. ACE2 binding and antibody evasion in enhanced 
transmissibility of XBB.1.5. Lancet Infect Dis. 2023;23(3):278-80.
33
Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA 
Covid-19 vaccine. N Engl J Med. 2020;383(27):2603-15.
34
Pfizer and BioNTech. Pfizer-BioNTech COVID-19 vaccine. Vaccines and Related 
Biological Products Advisory Committee meeting briefing document, 10 Dec 2020.
Available from: https://www.fda.gov/media/144245/download.
Accessed: 13 May 2022.
35
Pfizer. Pfizer and BioNTech confirm high efficacy and no serious safety concerns 
through up to six months following second dose in updated topline analysis of landmark 
COVID-19 vaccine study [press release]. Available from: 
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-
confirm-high-efficacy-and-no-serious. Published: 01 Apr 2021. 
Accessed: 25 Feb 2022.
36
FDA. Emergency use authorization (EUA) for an unapproved product: review 
memorandum. Pfizer-BioNTech COVID-19 vaccine BNT162b2 as a single booster 
dose. Available from: https://www.fda.gov/media/152432/download. 
Accessed: 07 Apr 2023.
37
Pfizer. Pfizer and BioNTech receive expanded U.S. FDA emergency use authorization 
of COVID-19 vaccine booster to include individuals 18 and older [press release]. 
Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-
and-biontech-receive-expanded-us-fda-emergency-use. Published: 19 Nov 2021. 
Accessed: 02 Jun 2022.
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PF-07302048 (BNT162b RNA-Based COVID-19 Vaccine)
Protocol C4591044
Final Protocol Amendment 6, 27 Jul 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
TMF Doc ID: 164.01
Page 174
38
Pfizer and BioNTech. Safety and efficacy data in support of a planned emergency use 
authorization amendment for a booster dose of the Pfizer-BioNTech COVID-19 vaccine 
in individuals 18 years of age and older. EUA 27034. 2021;7:10-2.
39
Pfizer and BioNTech. Vaccines and Related Biological Products Advisory Committee 
Meeting, 28 Jun 2022. Meeting Presentation: Pfizer-BioNTech COVID-19 Omicron-
modified vaccine options. Available from: 
https://www.fda.gov/media/159496/download. Accessed: 07 Apr 2023.
40
Wiemken TL, Khan F, Puzniak L, et al. Seasonal trends in COVID-19 cases, 
hospitalizations, and mortality in the United States and Europe.  Sci Rep. 
2023;13(1):3886.
41
Barouch DH. Covid-19 vaccines – immunity, variants, boosters. N Engl J Med. 
2022;387(11):1011-20.
42
CDC. Symptoms of COVID-19. Oct 2022.  Available from:  
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. 
Accessed: 05 Apr 2023.
43
FDA. Development and licensure of vaccines to prevent COVID-19. Guidance for 
industry. Available from: https://www.fda.gov/media/139638/download. 
Accessed: 07 Apr 2023.
44
CDC. People with certain medical conditions. Available from: 
https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-
medical-conditions.html. Accessed: 07 Apr 2023.
45
CDC. Information for healthcare providers about multisystem inflammatory syndrome 
in children (MIS-C). Available from: https://www.cdc.gov/mis/mis-c/hcp/index.html.
Accessed: 05 Apr 2023.
46
US Department of Health and Human Services, FDA, Center for Biologics Evaluation 
and Research. Guidance for industry: toxicity grading scale for healthy adult and 
adolescent volunteers enrolled in preventive vaccine clinical trials.  Rockville, MD: US 
Department of Health and Human Services; Sep 2007.
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