A PHASE 3, RANDOMIZED, OBSERVER-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF BNT162b2 WHEN COADMINISTERED WITH SEASONAL INACTIVATED INFLUENZA VACCINE (SIIV) IN ADULTS 18 THROUGH 64 YEARS OF AGE
Phase: PHASE3
Conditions: SARS-CoV-2 Infection, COVID-19
Sponsor: BioNTech SE

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Final Protocol Amendment 2, 09 March 2022
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A PHASE 3, RANDOMIZED, OBSERVER-BLIND TRIAL TO EVALUATE THE 
SAFETY AND IMMUNOGENICITY OF BNT162b2 WHEN COADMINISTERED 
WITH SEASONAL INACTIVATED INFLUENZA VACCINE (SIIV) IN ADULTS 18 
THROUGH 64 YEARS OF AGE
Study Sponsor:
BioNTech
Study Conducted By:
Pfizer
Study Intervention Number:
PF-07302048
Study Intervention Name:
BNT162b2 RNA-Based COVID-19 Vaccine
US IND Number:
EudraCT Number:
N/A
ClinicalTrials.gov ID:  
TBD
Protocol Number:
C4591030
Phase:
3
Brief Title: Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in 
Adults 18 Through 64 Years
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
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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.
CCI

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine) 
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Final Protocol Amendment 2, 09 March 2022
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Document History
Document
Version Date
Amendment 2
09 March 2022
Amendment 1
22 December 2021
Original protocol
13 August 2021
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.
Protocol Amendment Summary of Changes Table
Amendment 2 (09 March 2022)
Overall Rationale for the Amendment: Given the rapid and early COVID-19 vaccine 
third-dose (booster) rollout in southern hemisphere countries, the pool of potential study 
participants 18 through 64 years of age eligible to receive a third dose (booster) of 
BNT162b2 as part of this study will be significantly reduced. Also, it is possible that 
additional doses of BNT162b2 are required to improve protection against emerging variants; 
therefore, the protocol has been amended to assess coadministration of SIIV with a fourth
dose (booster) of BNT162b2.
Section # and Name
Description of 
Change
Brief Rationale Substantial or 
Nonsubstantial
Section 1.1 (Synopsis), 
Section 1.2 (Schema), 
Section 2 (Introduction), 
Section 4.3 (Justification for 
Dose), 
Section 5.1 (Inclusion 
Criteria)
Updated the study 
design to replace the 
third dose (booster) of 
BNT162b2 with a 
fourth dose (booster)
of BNT162b2.
Revised the eligibility 
criterion to indicate 
that participants with 
3 (rather than 2) prior 
doses of BNT162b2 
would be included in 
this study.
Added relevant data 
from publications and 
background 
information within the 
appropriate sections.
To increase the 
eligible 
population and 
evaluate a fourth
dose (booster)
Substantial

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Section # and Name
Description of 
Change
Brief Rationale Substantial or 
Nonsubstantial
Section 5.2 (Exclusion 
Criteria), 
Section 7.1 (Discontinuation 
of Study Intervention), 
Section 9.2 (Analysis Sets)
Modified exclusion 
criterion 5, excluding
those participants who 
had a positive
SARS-CoV-2 test
result within 28 days 
prior to Visit 1.
Associated sections 
were modified to 
reflect and align with 
modification of
exclusion criterion 5.
To increase the 
eligible 
population and 
better reflect the 
real-world 
situation
Substantial
Section 1.1 (Synopsis), 
Section 4.1 (Overall 
Design),
Section 5.5 (Criteria for 
Temporarily Delaying 
Enrollment/ Randomization/
Administration of Study 
Intervention),
Section 9.3.1.2.1
(Geometric Mean Ratios)
Removed
stratification on 
timing of the second 
dose of BNT162b2 
prior to Visit 1 
(Day 1) and added
stratification by
history of prior 
positive SARS-CoV-2 
test result (with 
history and without 
history).
Clarified that a 
positive SARS-CoV-2 
test (rapid antigen or 
NAAT) within
28 days will result in 
temporary delay of 
study intervention
administration.
To ensure
comparable 
populations 
within each 
group
Nonsubstantial

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Section # and Name
Description of 
Change
Brief Rationale Substantial or 
Nonsubstantial
Section 9.3.2 (Primary 
Endoint(s)/Estimand(s) 
Analysis)
Updated the linear 
regression model for 
the primary 
BNT162b2 
immunogenicity 
endpoint to include 
evidence of 
SARS-CoV-2 
infection as one of the 
factors (removing 
timing from the 
second dose at 
Visit 1).
To remain 
consistent with
the change of 
study design and 
the 
consideration of 
current possible 
high infection 
rate
Nonsubstantial
Section 8.3.8 (Adverse 
Events of Special Interest), 
Section 8.9.1 (Visit 1 –
Vaccination 1 (Day 1)
Added confirmed 
COVID-19 diagnosis 
or positive 
SARS-CoV-2 test 
result (by NAAT or 
rapid antigen test) as
an AESI.
Clarified that any 
history of COVID-19 
diagnosis or prior 
positive SARS-CoV-2 
test result by NAAT 
or rapid antigen test 
should be obtained as
part of medical history 
at Visit 1.
To ensure 
consistent 
reporting for 
analysis
Nonsubstantial
Section 5.3.1
(Contraception)
Updated from 
“highly” to 
“acceptable” effective 
contraception.
To align with 
wording in 
Section 10.4
Nonsubstantial
Section 1.3 (Schedule of 
Activities), 
Section 8.9.2 (Visit 3 –
[Follow-Up After 
Vaccination 2 – 28 to 42 
Days After Vaccination 2])
Clarified that study 
intervention container 
allocation is obtained 
at Visit 1 and Visit 2.
Procedure 
clarification
Nonsubstantial

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Section # and Name
Description of 
Change
Brief Rationale Substantial or 
Nonsubstantial
Section 6.8.1 (Prohibited 
During the Study)
Clarified that receipt 
of any nonstudy 
influenza vaccine 
during study 
participation is 
prohibited.
Administrative 
clarification
Nonsubstantial
Section 10.1.3 (Informed 
Consent Process), 
Section 10.3.4 (Reporting of 
SAEs), 
Section 10.4 (Appendix 4: 
Contraceptive and Barrier 
Guidance)
Added minor details 
to clarify associated 
sections.
Administrative 
clarifications
Nonsubstantial

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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................10
1. PROTOCOL SUMMARY...................................................................................................12
1.1. Synopsis ..................................................................................................................12
1.2. Schema ....................................................................................................................17
1.3. Schedule of Activities .............................................................................................18
2. INTRODUCTION ...............................................................................................................20
2.1. Study Rationale .......................................................................................................20
2.2. Background .............................................................................................................21
2.2.1. Clinical Overview.......................................................................................21
2.3. Benefit/Risk Assessment.........................................................................................23
2.3.1. Risk Assessment.........................................................................................25
2.3.2. Benefit Assessment.....................................................................................27
2.3.3. Overall Benefit/Risk Conclusion................................................................27
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................27
4. STUDY DESIGN.................................................................................................................29
4.1. Overall Design.........................................................................................................29
4.2. Scientific Rationale for Study Design.....................................................................29
4.2.1. Choice of Contraception/Barrier Requirements .........................................29
4.3. Justification for Dose ..............................................................................................30
4.4. End of Study Definition ..........................................................................................30
5. STUDY POPULATION......................................................................................................30
5.1. Inclusion Criteria.....................................................................................................30
5.2. Exclusion Criteria....................................................................................................31
5.3. Lifestyle Considerations..........................................................................................32
5.3.1. Contraception..............................................................................................32
5.4. Screen Failures ........................................................................................................33
5.5. Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention...........................33
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................33
6.1. Study Intervention(s) Administered........................................................................34
6.1.1. Concomitant Vaccine..................................................................................34

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6.1.2. Administration............................................................................................34
6.2. Preparation, Handling, Storage, and Accountability...............................................35
6.2.1. Preparation and Dispensing........................................................................36
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................36
6.3.1. Allocation to Study Intervention ................................................................36
6.3.2. Blinding Arrangements...............................................................................37
6.3.2.1. Blinding of Site Personnel.........................................................37
6.3.2.2. Blinding of the Sponsor.............................................................37
6.3.2.3. Breaking the Blind ....................................................................38
6.4. Study Intervention Compliance...............................................................................38
6.5. Dose Modification...................................................................................................38
6.6. Continued Access to Study Intervention After the End of the Study......................38
6.7. Treatment of Overdose............................................................................................38
6.8. Concomitant Therapy..............................................................................................39
6.8.1. Prohibited During the Study.......................................................................39
6.8.2. Permitted During the Study ........................................................................40
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................40
7.1. Discontinuation of Study Intervention ....................................................................40
7.2. Participant Discontinuation/Withdrawal From the Study.......................................41
7.2.1. Withdrawal of Consent...............................................................................41
7.3. Lost to Follow-Up ...................................................................................................42
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................42
8.1. Efficacy and/or Immunogenicity Assessments .......................................................43
8.1.1. Biological Samples.....................................................................................44
8.2. Safety Assessments .................................................................................................44
8.2.1. Physical Examinations................................................................................44
8.2.2. Vital Signs ..................................................................................................44
8.2.3. Electronic Diary..........................................................................................45
8.2.3.1. Grading Scales...........................................................................45
8.2.3.2. Local Reactions.........................................................................45
8.2.3.3. Systemic Events ........................................................................46

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8.2.3.4. Fever..........................................................................................47
8.2.3.5. Antipyretic Medication .............................................................48
8.2.4. Clinical Safety Laboratory Assessments ....................................................48
8.2.5. Pregnancy Testing ......................................................................................48
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................48
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......49
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................49
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................50
8.3.2. Method of Detecting AEs and SAEs ..........................................................50
8.3.3. Follow-Up of AEs and SAEs......................................................................50
8.3.4. Regulatory Reporting Requirements for SAEs...........................................50
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................51
8.3.5.1. Exposure During Pregnancy......................................................51
8.3.5.2. Exposure During Breastfeeding ................................................52
8.3.5.3. Occupational Exposure .............................................................53
8.3.6. Cardiovascular and Death Events...............................................................53
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................53
8.3.8. Adverse Events of Special Interest.............................................................53
8.3.8.1. Lack of Efficacy........................................................................54
8.3.9. Medical Device Deficiencies......................................................................54
8.3.10. Medication Errors.....................................................................................54
8.4. Pharmacokinetics ....................................................................................................55
8.5. Genetics...................................................................................................................55
8.5.1. Specified Genetics ......................................................................................55
8.6. Biomarkers ..............................................................................................................55
8.7. Immunogenicity Assessments.................................................................................55
8.8. Health Economics ...................................................................................................55
8.9. Study Procedures.....................................................................................................55
8.9.1. Visit 1 –Vaccination 1 (Day 1)...................................................................55
8.9.2. Visit 2 – Vaccination 2 – 28 to 42 Days After Visit 1................................58

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8.9.3. Visit 3 – (Follow-Up After Vaccination 2 – 28 to 42 Days After 
Vaccination 2)..................................................................................................59
8.10. Unscheduled Visit for a Grade 3 or Suspected Grade 4 Reaction ........................60
8.11. Additional Procedures for Monitoring of Potential Myocarditis or 
Pericarditis.................................................................................................................61
9. STATISTICAL CONSIDERATIONS ................................................................................61
9.1. Statistical Hypotheses .............................................................................................62
9.1.1. Statistical Hypothesis..................................................................................62
9.1.1.1. Statistical Hypothesis for BNT162b2 .......................................62
9.1.1.2. Statistical Hypothesis for SIIV..................................................62
9.1.2. Estimands....................................................................................................62
9.1.3. Multiplicity Adjustment..............................................................................63
9.2. Analysis Sets ...........................................................................................................63
9.3. Statistical Analyses .................................................................................................64
9.3.1. General Considerations...............................................................................64
9.3.1.1. Analysis for Binary Data...........................................................64
9.3.1.2. Analysis for Continuous Data ...................................................65
9.3.2. Primary Endpoint(s)/Estimand(s) Analysis ................................................66
9.3.3. Secondary Endpoint(s)/Estimand(s) Analysis............................................67
9.3.4. Tertiary/Exploratory Endpoint(s) ...............................................................68
9.4. Interim Analyses .....................................................................................................69
9.5. Sample Size Determination.....................................................................................69
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................71
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............71
10.1.1. Regulatory and Ethical Considerations ....................................................71
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................72
10.1.2. Financial Disclosure .................................................................................72
10.1.3. Informed Consent Process ........................................................................72
10.1.4. Data Protection .........................................................................................73
10.1.5. Committees Structure ...............................................................................73
10.1.5.1. Data Monitoring Committee ...................................................73

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10.1.6. Dissemination of Clinical Study Data ......................................................74
10.1.7. Data Quality Assurance ............................................................................75
10.1.8. Source Documents....................................................................................76
10.1.9. Study and Site Start and Closure ..............................................................77
10.1.10. Publication Policy...................................................................................77
10.1.11. Sponsor’s Qualified Medical Personnel .................................................78
10.2. Appendix 2: Clinical Laboratory Tests .................................................................79
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................80
10.3.1. Definition of AE .......................................................................................80
10.3.2. Definition of an SAE ................................................................................81
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................83
10.3.4. Reporting of SAEs....................................................................................87
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................88
10.4.1. Male Participant Reproductive Inclusion Criteria....................................88
10.4.2. Female Participant Reproductive Inclusion Criteria.................................88
10.4.3. Woman of Childbearing Potential ............................................................88
10.4.4. Contraception Methods.............................................................................89
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments .......91
10.6. Appendix 6: Alternative Measures During Public Emergencies ..........................93
10.6.1. Telehealth Visits.......................................................................................93
10.7. Appendix 7: Criteria for Allowing Inclusion of Participants With Chronic 
Stable HIV, HCV, or HBV Infection ........................................................................94
10.8. Appendix 8: Protocol Amendment History...........................................................95
10.9. Appendix 9: Abbreviations ...................................................................................97
11. REFERENCES ................................................................................................................100
LIST OF TABLES
Table 1.
Vaccine Administration per Group...........................................................35
Table 2.
Local Reaction Grading Scale ..................................................................46
Table 3.
Systemic Event Grading Scale..................................................................47
Table 4.
Scale for Fever..........................................................................................48

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Table 5.
Power Calculations for NI of the Coadministration Group to the  
Separate-Administration Group in SARS-CoV-2 Full-Length S-
Binding IgG Levels and HAI Titers .........................................................70

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1. PROTOCOL SUMMARY
1.1. Synopsis
Brief Title: Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 
18 Through 64 Years
Rationale
A pneumonia of unknown cause detected in Wuhan, China, was first reported in 
December 2019. In January 2020, the pathogen causing this outbreak was identified as a 
novel coronavirus 2019. The outbreak was declared a Public Health Emergency of 
International Concern on 30 January 2020. On 12 February 2020, the virus was officially 
named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the WHO 
officially named the disease caused by SARS-CoV-2 as coronavirus disease 2019 
(COVID-19). On 11 March 2020, the WHO upgraded the status of the COVID-19 outbreak 
from epidemic to pandemic, which continues to spread globally at high speed.
Numerous COVID-19 vaccines are currently in development globally, and several candidate 
COVID-19 vaccines have been shown to be efficacious in the prevention of COVID-19 in 
clinical studies and are now available under temporary or emergency authorizations.
The Pfizer-BioNTech COVID-19 vaccine (also referred to as BNT162b2) is administered
intramuscularly as a 2-dose series spaced a minimum of 21 days apart at a dose of 30 μg 
each, with the third dose (booster) being recommended at least 3 months after the second 
dose.
Like other COVID-19 vaccines recently developed, the long-term persistence of immunity 
and efficacy of BNT162b2 has yet to be studied.  Recent evolution of SARS-CoV-2 is 
resulting in an emergence of new virus variants with multiple mutations in the S protein, 
which might be associated with the lower efficacy of some of the current vaccines.  
Therefore, there is a need to continue research, including the evaluation of booster doses to 
overcome waning immunity and/or the development of modified vaccines.
Annual seasonal influenza vaccination is recommended in a number of countries around the 
world to prevent influenza in adults ≥18 years of age, particularly adults with risk factors for 
increased influenza morbidity and mortality, such as older adults and those with chronic 
medical conditions. Currently, BNT162b2 is recommended for vaccination of adults to 
prevent COVID-19 caused by SARS-CoV-2, and several countries have implemented 
booster programs for adults ≥18 years of age. Since the recommendations for COVID-19 
and influenza vaccination have considerable overlap, it is possible that both vaccines may 
need to be administered at the same time.
The SARS-CoV-2 variant Omicron (B.1.1.529 and BA lineages), also known as Omicron, is 
currently the dominant variant in many countries and, within the US, is responsible for 100% 
of sequenced COVID-19 cases as of the week ending 19 February 2022. Early data noted
that the vaccine effectiveness against hospitalization is 90% (95% CI: 80%-94%) for 
Omicron after 3 doses of any mRNA vaccine.  However, even with 3 vaccine doses, 

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neutralization against the Omicron variant was lower (by a factor of 4) than that against the 
Delta variant. The addition of a fourth dose (booster) may improve protection, with 
increased longevity of an immune response, provided it has a tolerable safety profile.
Israel has implemented a fourth dose (booster) of BNT162b2 in healthcare workers, adults 
60 years of age and older, and immunocompromised people who have received 3 prior doses 
of BNT162b2.  Preliminary data show up to 2 times higher protection against symptomatic 
disease and up to 3 times higher protection against severe disease compared to those who 
have received 3 doses of BNT162b2.
The purpose of this study is to assess the safety and immunogenicity of a fourth dose 
(booster) of BNT162b2 administered concomitantly with SIIV or 1 month apart in 
participants who have had 3 previous doses of BNT162b2 as per recommended dosing 
schedule.

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Objectives, Estimands, and Endpoints
Objectives
Estimands
Endpoints
Primary Safety Objective: 
Primary Safety Estimands:
Primary Safety Endpoints:
To describe the safety profile of 
BNT162b2 when coadministered with 
SIIV
In participants receiving 1 dose of 
BNT162b2 and SIIV or saline and 
having safety follow-up after 
vaccination from each vaccine group, 
the percentage of participants 
reporting:

Local reactions within 7 days 
after each vaccination

Systemic events within 7 days 
after each vaccination

AEs within 1 month after each
vaccination

SAEs from the first vaccination 
up to 1 month after the last 
vaccination

Local reactions (redness, 
swelling, and pain at the 
injection site)

Systemic events (fever, 
fatigue/tiredness, headache, 
chills, vomiting, diarrhea, new 
or worsened muscle pain, and
new or worsened joint pain)

AEs

SAEs
Primary BNT162b2 Immunogenicity 
Objective: 
Primary BNT162b2 
Immunogenicity Estimand:
Primary BNT162b2 
Immunogenicity Endpoint:
To demonstrate that the immune 
responses elicited by BNT162b2 when
coadministered with SIIV
(BNT162b2+SIIV) are noninferior to 
those elicited by BNT162b2 when 
administered alone
In participants in compliance with the 
key protocol criteria (evaluable 
participants):

GMR of full-length S-binding 
IgG levels 1 month after 
vaccination with BNT162b2 in 
the coadministration group to the 
IgG levels 1 month after 
vaccination with BNT162b2 in 
the separate-administration group

Full-length S-binding IgG 
levels
Primary SIIV Immunogenicity 
Objective:
Primary SIIV Immunogenicity
Estimand:
Primary SIIV Immunogenicity 
Endpoints:
To demonstrate that the immune 
responses elicited by SIIV when
coadministered with BNT162b2
(BNT162b2+SIIV) are noninferior
to those elicited by SIIV when 
administered alone
In evaluable participants:

GMR of the strain-specific HAI 
(or H3N2-neutralizing antibody) 
titers 1 month after vaccination 
with SIIV in the coadministration 
group to the corresponding HAI 
(or H3N2-neutralizing antibody) 
titers in the 
separate-administration group

Strain-specific HAI titers 

H3N2-neutralizing antibody 
titers (if H3N2-HAI titers 
cannot be obtained)
Secondary BNT162b2 
Immunogenicity Objective:
Secondary BNT162b2 
Immunogenicity Estimands:
Secondary BNT162b2 
Immunogenicity Endpoints:
To describe the immune responses 
elicited by BNT162b2 when 
coadministered with SIIV or 
administered alone
In evaluable participants from each 
vaccine group:

GMCs/GMTs before vaccination 
and 1 month after vaccination 
with BNT162b2

GMFR from before vaccination 
to 1 month after vaccination with 
BNT162b2

Full-length S-binding IgG 
levels

SARS-CoV-2–neutralizing 
titers (for a subset of 
approximately 200 participants)

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Secondary SIIV Immunogenicity 
Objective:
Secondary SIIV Immunogenicity 
Estimands:
Secondary SIIV Immunogenicity 
Endpoints:
To describe the immune responses 
elicited by SIIV when coadministered 
with BNT162b2 or administered alone
In evaluable participants from each 
vaccine group:

GMTs before vaccination and 
1 month after vaccination with 
SIIV

GMFR in strain-specific HAI 
titers from before vaccination to 
1 month after vaccination with 
SIIV

Strain-specific HAI titers 

H3N2-neutralizing antibody 
titers (if H3N2-HAI titers 
cannot be obtained)
Exploratory Immunogenicity 
Objective: 
Exploratory Immunogenicity 
Estimands
Exploratory Immunogenicity 
Endpoints: 
To further describe the immune 
responses elicited by SIIV when 
coadministered with BNT162b2 or 
administered alone 
In evaluable participants from each 
vaccine group: 

The percentage of participants 
with strain-specific HAI titers 
≥1:40 1 month after vaccination 
with SIIV

The percentage of participants 
with strain-specific HAI 
seroconversion 1 month after 
vaccination with SIIV 

The percentage of participants 
with H3N2 neutralization 
seroprotection 1 month after 
vaccination with SIIV

The percentage of participants 
with H3N2 neutralization 
seroconversion 1 month after 
vaccination with SIIV

Strain-specific HAI titers

H3N2-neutralizing antibody 
titers (if H3N2-HAI titers 
cannot be obtained)
Overall Design
This Phase 3, multicenter, randomized, observer-blind study, with a 2-arm parallel design,
will be conducted at investigator sites in the southern hemisphere. The purpose of this study 
is to assess the safety and immunogenicity of BNT162b2 and SIIV given together compared 
to the vaccines given 1 month apart. Approximately 1126 participants will be randomized at 
a ratio of 1:1 into the coadministration group and the separate-administration group stratified 
by age group (18-49 years and 50-64 years), and by history of positive SARS-CoV-2 test 
result by NAAT or rapid antigen test prior to randomization (with prior history of 
SARS-CoV-2 and without prior history of SARS-CoV-2). A single lot of SIIV is proposed 
for the study, and ideally this SIIV would be recommended for use in adults 18 through 64
years of age; however, ultimately the SIIV used may be determined by supply availability.
Local reactions (redness, swelling, and pain at the injection site) occurring at the BNT162b2 
or saline injection site within 7 days and systemic events (fever, headache, fatigue/tiredness,
chills, vomiting, diarrhea, new or worsening muscle pain, and new or worsening joint pain) 
occurring within 7 days after each vaccination (Visit 1 and Visit 2) will be prompted for and 
collected daily by the participant in an e-diary device or application. Use of antipyretic/pain 

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medications will also be prompted for and collected daily in the reactogenicity e-diary for 
7 days after each vaccination.
AEs and SAEs will be collected from the signing of informed consent through Visit 3
(approximately 1 month after Vaccination 2).
To assess immunogenicity, approximately 30 mL of blood will be collected at 3 study visits
from all participants: at Visit 1 (prior to Vaccination 1); at Visit 2 (prior to Vaccination 2); 
and at Visit 3 (1 month after Visit 2).
Number of Participants
Approximately 1126 participants will be randomized for a total of approximately 
900 evaluable participants (assuming a 20% nonevaluable rate).
Intervention Groups and Duration
Each participant will participate in the study for approximately 2 months. Based on an 
estimated 1- to 2-month enrollment, the study duration will be approximately 3 to 4 months. 
All participants will receive BNT162b2, SIIV, and saline via intramuscular injection.
Data Monitoring Committee or Other Independent Oversight Committee
An external DMC will be formed and will review cumulative unblinded data throughout the 
study.
Statistical Methods
The primary immunogenicity objectives will be evaluated by formal hypothesis tests for 
noninferiority of coadministration of BNT162b2 and SIIV (coadministration group) to 
administration of SIIV followed by BNT162b2 1 month later (separate-administration 
group), based on full-length S-binding IgG levels 1 month after vaccination with BNT162b2 
and strain-specific HAI titers (or H3N2-neutralizing antibody titers if H3N2-HAI titers 
cannot be obtained) 1 month after vaccination with SIIV. Noninferiority of the 
coadministration group to the separate-administration group will be declared for full-length 
S-binding IgG levels or an influenza strain if the lower limit of the 2-sided 95% CI for the 
GMR (coadministration group to separate-administration group) is >0.67. The primary 
immunogenicity objectives of the study will be achieved if noninferiority is met for the 
full-length S-binding IgG levels and for each of the influenza strains.

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The other immunogenicity objectives will be evaluated descriptively by GMCs/GMTs before 
vaccination and at 1 month after vaccination, GMFRs from before vaccination to 1 month 
after vaccination, percentage of participants with strain-specific HAI (or H3N2 
neutralization) seroconversion and strain-specific HAI titers ≥1:40 (or H3N2 neutralization 
seroprotection) 1 month after vaccination, and the associated 2-sided 95% CIs for full-length 
S-binding IgG levels and/or strain-specific HAI titers (or H3N2-neutralizing antibody titers).
The primary safety objective will be evaluated by descriptive summary statistics for local 
reactions, systemic events, AEs, and SAEs for each vaccine group.  A 3-tier approach will be 
used to summarize AEs.
1.2. Schema
Visit Number
1
2
3
Visit Description
Vaccination 1
Vaccination 2
(1 Month After 
Vaccination 1)
1-Month
Follow-Up
Visit
Participants having 
received 3 prior doses 
of 30 µg BNT162b2 
≥90 days prior to Visit 1 
randomization
Group 1
(563)
BNT162b2+ 
SIIV
Placebo 
Group 2
(563)
Placebo+
SIIV
BNT162b2
Immunogenicity 
blood draw
30 mL
30 mL
30 mL
Abbreviation: SIIV = seasonal inactivated influenza vaccine.

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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Visit Number
1
2
3
Visit Description
Vaccination 1
Vaccination 2
Follow-Up After
Vaccination 2
Visit Window
Day 1
28 to 42 Days After 
Vaccination 1
28 to 42 Days After 
Vaccination 2
Obtain informed consent
X
Assign participant number
X
Obtain demography and medical history data
X
Perform clinical assessmenta
X
Record BNT162b2 vaccine history
X
Collect and record nonstudy vaccinations
X
X
X
Measure temperature (oral)
X
X
Perform urine pregnancy test (if appropriate)
X
X
Confirm use of contraceptives (if appropriate)
X
X
X
Collect prohibited medication use
X
X
X
Confirm eligibility
X
X
Review temporary delay criteria
X
X
Obtain randomization number
X
Obtain study intervention container allocation using the IRT 
system
X
X

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Visit Number
1
2
3
Visit Description
Vaccination 1
Vaccination 2
Follow-Up After
Vaccination 2
Visit Window
Day 1
28 to 42 Days After 
Vaccination 1
28 to 42 Days After 
Vaccination 2
For participants who are HIV-positive, record latest HIV viral 
load and CD4 count
X
X
Collect blood sample for immunogenicity assessment 
30 mL
30 mL
30 mL
Administer study intervention
X
X
Assess acute reactions for at least 30 minutes after study 
intervention administration
X
X
Explain/review participant communication methods (including for 
reactogenicity e-diary completion), assist the participant with 
downloading the app, or issue provisioned device, if required
X
X
Provide/ensure participant has a thermometer and measuring 
device
X
X
Review reactogenicity e-diary data (daily review is optimal 
during the active diary period)
X
X
Review ongoing reactogenicity e-diary symptoms with participant 
and obtain stop dates
X
X
Ask the participant to contact the site staff or investigator if the 
participant experiences acute chest pain, shortness of breath, or 
palpitations.
X
X
Collect AEs and SAEs 
X
X
X
Request the participant return the e-diary or assist the participant 
to delete the application
X
Abbreviations: HIV = human immunodeficiency virus; IRT = interactive response technology.
a.
Including, if indicated, a physical examination.

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2. INTRODUCTION
BNT162b2 is an RNA-based COVID-19 vaccine that is currently being investigated for the 
prevention of COVID-19 in individuals ≥6 months of age.  On 02 December 2020, the 
MHRA in the UK granted a temporary authorization.1  On 11 December 2020, the US FDA 
issued an EUA for use in individuals 16 years of age and older.  BNT162b2 has now been 
granted a full marketing authorization, conditional marketing authorization, EUA, or 
temporary authorization in a total of more than 60 countries.2,3,4
2.1. Study Rationale
Like other COVID-19 vaccines recently developed, the long-term persistence of immunity 
and efficacy of BNT162b2 has yet to be studied.  Furthermore, the efficacy of BNT162b2 in 
the face of recurring emergence of new SARS-CoV-2 variants, with multiple mutations in the 
S protein, is unknown.  Recent evolution of SARS-CoV-2 is resulting in an emergence of 
new virus variants with multiple mutations in the S protein, which might be associated with 
the lower efficacy of some of the current vaccines.  Therefore, there is a need to continue 
research, including the evaluation of booster doses to overcome waning immunity and/or the 
development of modified vaccines.5
Annual seasonal influenza vaccination is recommended in many countries around the world 
to prevent influenza in adults ≥18 years of age, particularly adults with risk factors for 
increased influenza morbidity and mortality, such as older adults and those with chronic 
medical conditions.6 Since the recommendations for COVID-19 and influenza vaccination 
have considerable overlap, it is possible that both vaccines may need to be administered at 
the same time.7
The SARS-CoV-2 variant Omicron (B.1.1.529 and BA lineages), also known as Omicron, is 
currently the dominant variant in many countries and, within the US, is responsible for 100% 
of sequenced COVID-19 cases as of the week ending 19 February 2022.8,9 Early data noted
that the vaccine effectiveness against hospitalization is 90% (95% CI: 80%-94%) for 
Omicron after 3 doses of any mRNA vaccine.10 However, even with 3 vaccine doses, 
neutralization against the Omicron variant was lower (by a factor of 4) than that against the 
Delta variant.11 The addition of a fourth dose (booster) may improve protection, with 
increased longevity of an immune response, provided it has a tolerable safety profile.
Israel has implemented a fourth dose (booster) of BNT162b2 in healthcare workers, adults 
60 years of age and older, and immunocompromised people who have received 3 prior doses 
of BNT162b2.  Preliminary data show up to 2 times higher protection against symptomatic 
disease and up to 3 times higher protection against severe disease compared to those who 
have received 3 doses of BNT162b2.12
The purpose of this study is to assess the safety and immunogenicity of a fourth dose 
(booster) of BNT162b2 administered concomitantly with SIIV or 1 month apart in 
participants who had 3 previous doses of BNT162b2 as per the recommended dosing 
schedule.

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2.2. Background
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China.  
In January 2020, it became clear that 2019-nCoV was the underlying cause.  The outbreak 
was declared a Public Health Emergency of International Concern on 30 January 2020.  On 
11 February 2020, the virus was officially named as SARS-CoV-2, and the WHO officially 
named the disease caused by SARS-CoV-2 as COVID-19.13,14  SARS-CoV-2 infections and 
the resulting disease, COVID-19, have spread globally, and on 11 March 2020, the WHO 
characterized the COVID-19 outbreak as a pandemic.15  To date, more than 148 million 
people have been infected with SARS-CoV-2 and >3 million have died, demonstrating an 
urgent need for efficacious vaccines.16
Numerous COVID-19 vaccines are currently in development globally, and several candidate 
COVID-19 vaccines have been shown to be efficacious in the prevention of COVID-19 in 
clinical studies and are now available under full marketing, temporary, or emergency 
authorizations.17
The Pfizer-BioNTech COVID-19 vaccine (also referred to as BNT162b2) is administered
intramuscularly as a 2-dose series spaced a minimum of 21 days apart at a dose of 30 μg 
each, with the third dose (booster) being recommended at least 3 months after the second 
dose.18,19
2.2.1. Clinical Overview
Study C4591001 (NCT04368728) is an ongoing Phase 1/2/3 trial in ~46,000 participants 
designed to generate safety, tolerability, immunogenicity, and efficacy data from a novel 
RNA-based vaccine candidate.20  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 (BNT162b1 or BNT162b2) and dose level (10 µg, 20 µg, 30 µg, or 100 µg 
[for BNT162b1]); Phase 2/3: an expanded-cohort and efficacy part for the selected vaccine 
candidate (BNT162b2).
The available immunogenicity data from Phase 1 participants show that BNT162b2 induced 
a robust IgG-binding response to S1 and a SARS-CoV-2–neutralizing response.  
Immunogenicity substantially increased following the second dose of vaccine.  BNT162b2 
induces a strong antigen-specific Th1-skewed CD4+ response and a strong antigen-specific 
CD8+ response.  BNT162b2 was selected from the Phase 1 part of the study based on the 
overall safety, tolerability, and immunogenicity.  In a mid–November 2020 analysis of 
36,621 participants randomized 1:1 to vaccine or placebo, who were included in the 
per-protocol efficacy analysis population of participants without evidence of SARS-CoV-2 
infection prior to 7 days after completion of the vaccination schedule, the efficacy in 
preventing confirmed COVID-19 occurring at least 7 days after the second dose of vaccine 
was 95.0%, with 8 COVID-19 cases in the active vaccine group and 162 COVID-19 cases in 
the placebo group.  Subgroup analyses of the primary efficacy endpoint showed similar 
efficacy point estimates across age groups, sexes, racial and ethnic groups, and participants 

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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.21
In a subsequent analysis of 927 confirmed symptomatic cases of COVID-19, an efficacy rate 
of 91.3% was observed for BNT162b2 in preventing such cases occurring between 7 days to 
6 months after the second dose.22  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.21
The most common solicited adverse reactions were injection site reactions (84.1%), fatigue 
(62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), and 
fever (14.2%); severe adverse reactions occurred in 0.0% to 4.6% of participants, were more 
frequent after Dose 2 than after Dose 1, and were generally less frequent in participants 
≥55 years of age (≤2.8%) as compared to younger participants (≤4.6%).  The frequency of 
SAEs was low (<0.5%), without meaningful imbalances between study arms.  Otherwise, 
there were no notable patterns or numerical imbalances between vaccine groups for specific 
categories of nonserious AEs (including other neurologic, neuroinflammatory, and 
thrombotic events) that would suggest a causal relationship to BNT162b2.  With the 
exception of more frequent, generally mild to moderate reactogenicity in participants 
<55 years of age, the safety profile of BNT162b2 was generally similar across age groups, 
sexes, ethnic and racial groups, participants with or without medical comorbidities, and 
participants with or without evidence of prior SARS-CoV-2 infection at enrollment.21
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,

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including severe COVID-19.23 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.24 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 BNT162b2.25  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.26,27
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.28
2.3. Benefit/Risk Assessment
There is an ongoing global pandemic of COVID-19 with several SARS-CoV-2 vaccines now 
in use under full marketing authorizations, conditional 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 studies 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.
In the C4591001 study, BNT162b2 has been shown to elicit increased local and systemic 
adverse reactions as compared to those in the placebo arm, usually lasting a few days.  The 
most common solicited adverse reactions were injection site reactions (84.1%), fatigue 
(62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), and 
fever (14.2%).21  Adverse reactions characterized as reactogenicity were generally mild to 
moderate.  The number of participants reporting hypersensitivity-related AEs was 
numerically higher in the vaccine group compared with the placebo group (137 [0.63%] vs 
111 [0.51%]).  Severe adverse reactions occurred in 0.0% to 4.6% of participants, were more 
frequent after Dose 2 than after Dose 1, and were generally less frequent in participants
≥55 years of age (≤2.8%) as compared to younger participants (≤4.6%).  Among reported 
unsolicited AEs, lymphadenopathy occurred much more frequently in the active vaccine 

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group than the placebo group and is plausibly related to vaccination.  SAEs, while 
uncommon (<1.0%), represented medical events that occur in the general population at 
similar frequency as observed in the study.21
No specific safety concerns were identified in subgroup analyses by age, race, ethnicity, 
medical comorbidities, or prior SARS-CoV-2 infection.  The risks are based on the observed 
safety profile to date, which shows mostly mild reactogenicity, low incidence of severe or 
serious events, and no clinically concerning safety observations.  The preponderance of 
severe cases of COVID-19 in the placebo group relative to the BNT162b2 group (9 of 10) 
suggests no evidence of VAED.21
In the latest analysis from C4591001, vaccine safety has been evaluated in more than 44,000 
participants ≥16 years of age, with more than 12,000 vaccinated participants having at least 
6 months of follow-up after their second dose.  No serious safety concerns have been 
observed in this timeframe.  Side effects observed in this analysis were generally consistent 
with previously reported results.22
The tolerability profile of fourth doses of BNT162b2 has yet to be described in 
peer-reviewed publications; however, fourth doses have been administered in some 
countries.12  Based on preliminary data published, it is expected that the potential benefits 
outweigh the risks.
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 immunoresponses to overcome waning immunity.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of BNT162b2 may be found in the IB, which is the SRSD for this study.
The SRSD for the SIIV is the product information for the country where the vaccine was 
procured.

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2.3.1. Risk Assessment
Identified/Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): BNT162b2 RNA-Based COVID-19 Vaccine
Local reactions and systemic events may occur 
(injection site redness, injection site swelling, and 
injection site pain; fever, fatigue, headache, chills, 
muscle pain, and joint pain) following vaccination.
These are common adverse reactions seen with 
other vaccines as well as the COVID-19 vaccine.  
The most common events reported in Study 
C4591001 were mild to moderate pain at the 
injection site, fatigue, and headache.21

Local reactions and systemic events will be 
recorded in an e-diary.

All study participants will be observed for at 
least 30 minutes after vaccination.
Safety profile of a novel vaccine not yet fully 
characterized.
Adverse reactions (risks) identified from the 
postauthorization safety data include the following: 
anaphylaxis, other hypersensitivity reactions 
(eg, rash, pruritus, urticaria, angioedema), pain in 
extremity (injected arm), vomiting, and diarrhea.
Please refer to the latest version of the IB for the 
most recent safety information.
Data available from Study C4591001 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.21
Postauthorization safety data surveillance has 
confirmed the safety profile observed in Study 
C4591001 and has resulted in identification of some 
additional adverse reactions (risks) as noted in this 
table.

Collection of AEs from signing of the ICD 
through 1 month after the booster vaccination.

Collection of SAEs from signing of the ICD 
through 1 month after the booster vaccination.

DMC review throughout the study to review all 
safety data.

All participants will be observed for at least 
30 minutes after vaccination.
Theoretical risk for COVID-19 enhancement.
Disease enhancement has been seen following 
vaccination with RSV, feline coronavirus, and 
Dengue virus vaccines.  It is a modified and/or 
severe presentation of an infectious disease 
affecting individuals exposed to the wild-type 
pathogen after having received vaccine designed to 
prevent infection.  No evidence of disease 
enhancement has been seen in large-scale clinical 
study of BNT162b2 in humans or in 
postauthorization surveillance.

Monitoring for cases of COVID-19 developing 
during the study, which will be reported as 
AEs.

Assessments of individual cases for disease 
enhancement is challenging based on current 
understanding of mechanism of pathogenesis, 
thus evaluations of any adverse or unexpected 
imbalances in severe COVID-19 cases may 
provide insight to a potential signal for this 
theoretical risk.

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Identified/Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Very rare cases of anaphylaxis, myocarditis, and 
pericarditis have been reported after authorization in 
recipients of BNT162b2.
Anaphylaxis: The estimated rate is 5.0 per million 
doses administered.
Myocarditis and pericarditis: Very rare cases of 
myocarditis and pericarditis have been reported 
following vaccination with mRNA COVID-19 
vaccines. Typically, the cases have occurred more 
often in younger men and after the second dose of 
the vaccine and within 14 days after vaccination. 
These are generally mild cases, and individuals tend 
to recover within a short time following standard 
treatment and rest. Healthcare professionals should 
be alert to the signs and symptoms of myocarditis 
and pericarditis in vaccine recipients.
Specific reference to these risks is made within the 
ICD, with instruction to contact a healthcare 
professional if a case is suspected.
For anaphylaxis, there is an on-site 30-minute 
observation period after vaccination.
Instructions for handling suspected cases of 
myocarditis and pericarditis are found in
Section 8.11.
Study Procedures
Participants will be required to attend healthcare 
facilities during the global SARS-CoV-2 pandemic.
Without appropriate social distancing and PPE, 
there is a potential for increased exposure to 
SARS-CoV-2.  In addition, local travel and 
movement restrictions could impact study visit 
conduct and protocol compliance.

Pfizer will work with sites to ensure an 
appropriate COVID-19 prevention strategy and 
to mitigate the impact of local travel 
restrictions.

Monitoring for cases of COVID-19 developing 
during the study, which will be reported as 
AEs.
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 fourth dose (booster) of an efficacious or potentially efficacious
COVID-19 vaccine that may convey a longer duration of protection during a global 
pandemic

Contributing to research to help others in a time of global pandemic

Receipt of a licensed influenza vaccine
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risks to participants participating in the 
study, the potential risks identified in association with BNT162b2 are justified by the 
anticipated benefits that may be afforded to healthy participants.
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectives
Estimands
Endpoints
Primary Safety Objective: 
Primary Safety Estimands:
Primary Safety Endpoints: 
To describe the safety profile of 
BNT162b2 when coadministered 
with SIIV
In participants receiving 1 dose of 
BNT162b2 and SIIV or saline and 
having safety follow-up after 
vaccination from each vaccine 
group, the percentage of participants 
reporting:

Local reactions within 7 days 
after each vaccination

Systemic events within 7 days 
after each vaccination

AEs within 1 month after each
vaccination

SAEs from the first vaccination 
up to 1 month after the last 
vaccination 

Local reactions (redness, 
swelling, and pain at the 
injection site)

Systemic events (fever, 
fatigue/tiredness, headache, 
chills, vomiting, diarrhea, 
new or worsened muscle 
pain, and new or worsened 
joint pain)

AEs

SAEs
Primary BNT162b2 
Immunogenicity Objective: 
Primary BNT162b2 
Immunogenicity Estimand:
Primary BNT162b2 
Immunogenicity Endpoint:
To demonstrate that the immune 
responses elicited by BNT162b2 
when coadministered with SIIV
(BNT162b2+SIIV) are noninferior
to those elicited by BNT162b2
when administered alone
In participants in compliance with 
the key protocol criteria (evaluable 
participants):

GMR of full-length S-binding 
IgG levels 1 month after 
vaccination with BNT162b2 in 
the coadministration group to 
the IgG levels 1 month after 
vaccination with BNT162b2 in 
the separate-administration 
group

Full-length S-binding IgG 
levels

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Primary SIIV Immunogenicity 
Objective:
Primary SIIV Immunogenicity
Estimand:
Primary SIIV Immunogenicity 
Endpoints:
To demonstrate that the immune 
responses elicited by SIIV when
coadministered with BNT162b2
(BNT162b2+SIIV) are noninferior
to those elicited by SIIV when 
administered alone
In evaluable participants:

GMR of the strain-specific HAI 
(or H3N2-neutralizing antibody) 
titers 1 month after vaccination 
with SIIV in the 
coadministration group to the 
corresponding HAI 
(or H3N2-neutralizing antibody) 
titers in the 
separate-administration group

Strain-specific HAI titers 

H3N2-neutralizing antibody 
titers (if H3N2-HAI titers 
cannot be obtained)
Secondary BNT162b2 
Immunogenicity Objective:
Secondary BNT162b2 
Immunogenicity Estimands:
Secondary BNT162b2
Immunogenicity Endpoints:
To describe the immune responses 
elicited by BNT162b2 when 
coadministered with SIIV or 
administered alone
In evaluable participants from each 
vaccine group:

GMCs/GMTs at before 
vaccination and 1 month after 
vaccination with BNT162b2

GMFR from before vaccination 
to 1 month after vaccination 
with BNT162b2

Full-length S-binding IgG 
levels

SARS-CoV-2–neutralizing 
titers (for a subset of 
approximately 200 
participants)
Secondary SIIV 
Immunogenicity Objective:
Secondary SIIV Immunogenicity 
Estimands:
Secondary SIIV 
Immunogenicity Endpoints:
To describe the immune responses 
elicited by SIIV when 
coadministered with BNT162b2 
or administered alone
In evaluable participants from each 
vaccine group:

GMTs before vaccination and 
1 month after vaccination with 
SIIV

GMFR in strain-specific HAI 
titers from before vaccination to 
1 month after vaccination with 
SIIV

Strain-specific HAI titers

H3N2-neutralizing antibody 
titers (if H3N2-HAI titers 
cannot be obtained)
Exploratory Immunogenicity 
Objective: 
Exploratory Immunogenicity 
Estimands
Exploratory Immunogenicity 
Endpoints: 
To further describe the immune 
responses elicited by SIIV when 
coadministered with BNT162b2 
or administered alone
In evaluable participants from each 
vaccine group: 

The percentage of participants 
with strain-specific HAI titers 
≥1:40 1 month after vaccination 
with SIIV

The percentage of participants 
with strain-specific HAI 
seroconversion 1 month after 
vaccination with SIIV 

The percentage of participants 
with H3N2 neutralization
seroprotection 1 month after 
vaccination with SIIV

The percentages of participants 
with H3N2 neutralization
seroconversion 1 month after 
vaccination with SIIV

Strain-specific HAI titers

H3N2-neutralizing antibody 
titers (if H3N2-HAI titers 
cannot be obtained)

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4. STUDY DESIGN
4.1. Overall Design
This Phase 3, multicenter, randomized, observer-blind study with a 2-arm parallel design will 
be conducted at investigator sites in the southern hemisphere. The purpose of this study is to 
assess the safety and immunogenicity of BNT162b2 and SIIV given together compared to the 
vaccines given 1 month apart. Approximately 1126 participants will be randomized at a ratio 
of 1:1 into the coadministration group and the separate-administration group stratified by age 
group (18-49 years and 50-64 years) and by history of positive SARS-CoV-2 test result by 
NAAT or rapid antigen test prior to randomization (with prior history of SARS-CoV-2 and 
without prior history of SARS-CoV-2). A single lot of SIIV is proposed for the study, and 
ideally this SIIV would be recommended for use in adults 18 through 64 years of age; 
however, ultimately the SIIV used may be determined by supply availability.
Local reactions (redness, swelling, and pain at the injection site) occurring at the BNT162b2 
or saline injection site within 7 days and systemic events (fever, headache, fatigue/tiredness,
chills, vomiting, diarrhea, new or worsening muscle pain, and new or worsening joint pain) 
occurring within 7 days after each vaccination (Visit 1 and Visit 2) will be prompted for and 
collected daily by the participant in an e-diary device or application. Use of antipyretic/pain 
medications will also be prompted for and collected daily in the reactogenicity e-diary for 
7 days after each vaccination.
AEs will be collected from the signing of informed consent through Visit 3 (approximately 
1 month after Vaccination 2). SAEs will be collected from the signing of informed consent 
through Visit 3.
To assess immunogenicity, approximately 30 mL of blood will be collected from all 
participants at 3 study visits: at Visit 1 (prior to Vaccination 1); at Visit 2 (prior to 
Vaccination 2); and at Visit 3 (1 month after Visit 2).
Each participant will participate in the study for approximately 2 months. Based on an 
estimated 1- to 2-month enrollment, the study duration will be approximately 3 to 4 months. 
All participants will receive BNT162b2, SIIV, and saline via intramuscular injection. 
4.2. Scientific Rationale for Study Design
See Section 2.1.
4.2.1. Choice of Contraception/Barrier Requirements
Human reproductive safety data are not available for BNT162b2; therefore, the use of a 
highly effective method of contraception is required (see Appendix 4). However, there is no 
suspicion of human teratogenicity based on the intended pharmacology of the compound.

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4.3. Justification for Dose
Based on data from the Phase 1 component of Study 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.  This is the dose that was shown to be effective and has been approved for use 
and authorized for temporary or emergency use in multiple countries worldwide, and has 
been recommended as a third dose (booster). The same dose will therefore be used in this 
study as a fourth dose (booster).
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study.
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last visit.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. Use of a 
prescreener for study recruitment purposes will include collection of information that reflects 
the enrollment of a diverse participant population including, where permitted under local 
regulations, age, sex, race, and ethnicity.
The following eligibility criteria are designed to select participants for whom participation in 
the study is considered appropriate. All relevant medical and nonmedical conditions should 
be taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Participants 18 through 64 years of age, inclusive, at the time of consent.

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, 
lifestyle considerations, and other study procedures.

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3. Adults determined by clinical assessment, including medical history and clinical 
judgment, to be eligible for the study, including adults with preexisting stable disease, 
defined as disease not requiring significant change in therapy in the previous 6 weeks or 
hospitalization for worsening disease within 12 weeks before receipt of study 
intervention.
Note: Healthy participants with preexisting stable disease, defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease during 
the 6 weeks before enrollment, can be included. Specific criteria for participants with 
known stable infection with HIV, HCV, or HBV can be found in Appendix 7, 
Section 10.7.
4. Have received 3 prior doses of 30 µg BNT162b2, with the third dose being at least
90 days before Visit 1 (Day 1). Documented confirmation of prior BNT162b2 receipt 
must be obtained prior to randomization.
Informed Consent:
5. Capable of giving personal signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in this 
protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Other medical or psychiatric condition, including recent (within the past year) or active 
suicidal ideation/behavior, or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the 
study.
2. Allergy to egg proteins (egg or egg products) or chicken proteins.
3. History of Guillain-Barré syndrome.
4. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study intervention(s).
5. A positive SARS-CoV-2 test result (either by NAAT or rapid antigen test) within 28 days 
of Visit 1 (Day 1).
6. Immunocompromised individuals with known or suspected immunodeficiency, as 
determined by history and/or laboratory/physical examination.

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7. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
8. Women who are pregnant or breastfeeding.
Prior/Concomitant Therapy:
9. Vaccination with any influenza vaccine <6 months before study intervention
administration, or planned receipt of any licensed or investigational nonstudy influenza 
vaccine during study participation.
10. Individuals who receive treatment with radiotherapy or immunosuppressive therapy, 
including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are 
administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for 
COPD, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, 
intrabursal, or topical (skin or eyes) corticosteroids are permitted.
11. Receipt of blood/plasma products or immunoglobulin, from 60 days before study 
intervention administration or planned receipt throughout the study.
12. Receipt of any passive antibody therapy specific to COVID-19 from 90 days before study 
intervention administration or planned receipt throughout the study.
13. Prior receipt of any COVID-19 vaccine other than BNT162b2 or receipt of more than 3
prior doses of BNT162b2.
Prior/Concurrent Clinical Study Experience:
14. Participation in other studies involving study intervention within 28 days prior to study 
entry and/or during study participation.
Other Exclusions:
15. Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of 
the study, site staff otherwise supervised by the investigator, and their respective family 
members.
5.3. Lifestyle Considerations
5.3.1. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Section 10.4, 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 

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participant’s chart (participants need to affirm their consistent and correct use of at least 1 of 
the selected methods of contraception) considering that their risk for pregnancy may have 
changed since the last visit.  In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet 
the CONSORT publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility 
criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Administration of 
Study Intervention 
The following conditions are temporary or self-limiting and a participant may be vaccinated 
once the condition(s) has/have resolved and no other exclusion criteria are met.  Participants 
meeting these criteria at Vaccination 1 will be considered screen failures if enrollment has 
closed once the condition(s) has/have resolved.
1. Current febrile illness (oral temperature ≥38.0°C [≥100.4°F]) or other acute illness within 
48 hours before study intervention administration.  This includes a positive SARS-CoV-2 
test result (NAAT or rapid antigen test) within 28 days.
2. Receipt of any nonstudy vaccine within 28 days before study intervention administration.
3. Anticipated receipt of any nonstudy vaccine within 28 days after study intervention 
administration.
4. Receipt of short-term (<14 days) systemic corticosteroids.  Study intervention 
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 28 days.  Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or 
eyes) corticosteroids are permitted.
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.

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6.1. Study Intervention(s) Administered
Intervention Name
BNT162b2 
(BNT162 RNA-LNP Vaccine Utilizing modRNA)
Type
Vaccine
Dose Formulation
modRNA – single-dose vial
Unit Dose Strength(s)
250 µg/0.5 mL
Dosage Level(s) 
30 µg (administered as a 0.3-mL dose)
Route of Administration
Intramuscular injection
Use
Experimental
IMP or NIMP
IMP
Sourcing
Provided centrally by the sponsor
Packaging and Labeling
Study intervention will be provided in a glass vial as open-label supply.  
Each vial will be labeled as per country requirement.
Additional Intervention 
Name
Saline Placebo
Type
Placebo
Dose Formulation
Normal saline (0.9% sodium chloride solution for injection) – single-dose vial
Unit Dose Strength(s)
N/A
Dosage Level(s) 
N/A
Route of Administration
Intramuscular injection
Use
Placebo
IMP or NIMP
IMP
Sourcing
Provided centrally by the sponsor
Packaging and Labeling
Study intervention will be provided in a glass or plastic vial as open-label 
supply.  Each vial will be labeled as per country requirement.
6.1.1. Concomitant Vaccine
Licensed SIIV containing strains of influenza viruses that are antigenically like the annually 
recommended mammalian cell-produced or egg-produced strains will be supplied to the site 
and packaged as commercial supplies. Pfizer will provide this vaccine; however, with
approval by the sponsor, a site may independently procure the study-specific SIIV rather than 
receive shipment of SIIV from the sponsor. SIIV will be shipped and stored as per the 
commercial package insert and commercial label. Administration of SIIV will be recorded in 
the CRF.
6.1.2. Administration
The vaccines and placebo will be administered by an unblinded third-party site staff member 
at Visit 1 and Visit 2.

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Table 1.
Vaccine Administration per Group
Visit 1 – Vaccination 1
Visit 2 – Vaccination 2
Group 1
Left deltoid
0.3 mL of BNT162b2 injected 
intramuscularly
0.3 mL of saline injected intramuscularly
Group 1
Right deltoid
SIIV injected intramuscularly 
N/A
Group 2
Left deltoid
0.3 mL of saline injected intramuscularly
0.3 mL of BNT162b2 injected 
intramuscularly
Group 2
Right deltoid
SIIV injected intramuscularly
N/A
Abbreviation: SIIV = seasonal inactivated influenza vaccine. 
Standard vaccination practices must be observed, and the vaccine must not be injected into 
the blood vessels. Appropriate medication and other supportive measures for the 
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, 
GCP-trained, and vaccine-experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacist, or medical assistant) as allowed by 
local, state, and institutional guidance.
Study intervention administration details will be recorded on the CRF.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention.
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study interventions
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated recording) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff. At a minimum, daily minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request. Data for nonworking days must indicate the minimum and maximum 
temperatures since previously documented for all site storage locations upon return to 
business.
3. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with any actions taken. The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible. Once an excursion is identified, the study intervention must 
be quarantined and not used until Pfizer provides permission to use the study 
intervention. Specific details regarding the definition of an excursion and information the 
site should report for each excursion will be provided to the site in the IP manual.

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4. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the label.
5. Study interventions should be stored in their original containers.
6. See the IP manual, for storage conditions of the study intervention once diluted.
7. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records), such as the IPAL or 
sponsor-approved equivalent. All study interventions will be accounted for using a study 
intervention accountability form/record.
8. Further guidance and information for the final disposition of unused study interventions 
are provided in the IP manual. All destruction must be adequately documented. If 
destruction is authorized to take place at the investigator site, the investigator must ensure 
that the materials are destroyed in compliance with applicable environmental regulations, 
institutional policy, and any special instructions provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual.
6.2.1. Preparation and Dispensing
See the IP manual for instructions on how to prepare the study intervention for 
administration. Study intervention should be prepared and dispensed by an appropriately 
qualified and experienced member of the study staff (eg, physician, nurse, physician’s 
assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as allowed by 
local, state, and institutional guidance. A second staff member will verify the dispensing.
Study intervention will be prepared by qualified unblinded site personnel according to the IP 
manual. The study intervention will be administered in a blinded fashion to the participants.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Allocation (randomization) of participants to vaccine groups will proceed through the use of 
an IRT system (IWR). The site personnel (study coordinator or specified designee) will be 
required to enter or select information including but not limited to the user’s ID and 
password, the protocol number, and the participant number. The site personnel will then be 
provided with a randomization number.  The IRT system will provide a confirmation report 
containing the participant number, randomization number, and study intervention container
allocation assigned.  This report will be provided to blinded or unblinded site staff, as 
appropriate, relative to the study phase blinding arrangements and must be stored in the site’s 
blinded or unblinded files as appropriate.

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The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.3.2. Blinding Arrangements
6.3.2.1. Blinding of Site Personnel
In this observer-blinded study, the study staff receiving, storing, dispensing, preparing, and 
administering the study interventions will be unblinded.  All other study and site personnel, 
including the investigator, investigator staff, and participants, will be blinded to study 
intervention assignments.  In particular, the individuals who evaluate participant safety will 
be blinded.  Because there are 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.
6.3.2.2. Blinding of the Sponsor
The majority of sponsor/Pfizer staff will be blinded to study intervention allocation until the 
analysis at the completion of the study.  All laboratory testing personnel performing serology 
assays will remain blinded to the study intervention assigned/received throughout the study.  
The following sponsor/Pfizer staff, who will have no part in the blinded conduct of the study, 
will be unblinded (further details will be provided in a data blinding plan):

Those study team members who are involved in ensuring that protocol requirements for 
study intervention preparation, handling, allocation, and administration are fulfilled at the 
site will be unblinded for the duration of the study (eg, unblinded study manager, 
unblinded clinical research associate).

Unblinded clinician(s), who are not direct members of the study team and will not 
participate in any other study-related activities, will review unblinded protocol 
deviations.

An unblinded statistician and programmer supporting interactions with, and analyses for, 
the DMC (see Section 10.1.5)

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6.3.2.3. Breaking the Blind
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s study 
intervention assignment is warranted. Participant safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the sponsor prior to 
unblinding a participant’s vaccine assignment unless this could delay further management of 
the participant. If a participant’s vaccine assignment is unblinded, the sponsor must be 
notified within 24 hours after breaking the blind. The date and reason that the blind was 
broken must be recorded in the source documentation and CRF.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered will be recorded in the source documents and recorded in the CRF. The blinded 
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.
6.5. Dose Modification
Not applicable.
6.6. Continued Access to Study Intervention After the End of the Study
No study intervention will be provided to participants at the end of their study participation.
6.7. Treatment of Overdose
For this study, any dose of study intervention greater than 1 dose of study intervention within 
a 24-hour time period will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose as well as the duration of the overdose in the 
CRF.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.

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Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
6.8. Concomitant Therapy
The following concomitant medications and vaccinations will be recorded in the CRF:

Any vaccinations received from 28 days prior to study enrollment through Visit 3.

Prohibited medications listed in Section 6.8.1 will be recorded to include start and stop 
dates, name of the medication, dose, unit, route, and frequency.
6.8.1. 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 and may require 
vaccinations to be discontinued in that participant; however, it is anticipated that the 
participant would not be withdrawn from the study (see Section 7).  Medications should not 
be withheld if required for a participant’s medical care.

Unless considered medically necessary, no vaccines other than the study intervention 
should be administered within 28 days before and 28 days after each study vaccination.

Vaccination with any influenza vaccine within 6 months (182 days) before study 
intervention administration or receipt of any nonstudy influenza vaccine during study 
participation is prohibited.

Receipt of chronic systemic treatment with known immunosuppressant medications, or 
radiotherapy, within 60 days before enrollment through conclusion of the study.

Receipt of systemic corticosteroids (≥20 mg/day of prednisone or equivalent) for 
≥14 days is prohibited from 28 days prior to enrollment through 28 days after 
administration of the last study intervention.

Receipt of blood/plasma products, immunoglobulins, or monoclonal antibodies, from 
60 days before study intervention administration, or receipt of any passive antibody 
therapy (including monoclonal antibodies) specific to COVID-19 within 90 days before 
enrollment through conclusion of the study.

Receipt of any other (nonstudy) coronavirus vaccine at any time during study 
participation is prohibited.

Prophylactic antipyretics and other pain medication to prevent symptoms associated with 
study intervention administration are not permitted.  However, if a 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.

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6.8.2. Permitted During the Study
The use of antipyretics and other pain medication to treat symptoms associated with study 
intervention administration or ongoing conditions is permitted.
Medications and vaccines other than those described as prohibited in Section 6.8.1 required 
for treatment of preexisting conditions or acute illness are permitted.
Inhaled, topical, or localized injections of corticosteroids (eg, intra-articular or intrabursal 
administration) are permitted.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention.  Reasons for permanent discontinuation of study intervention include the 
following: AEs; participant request; investigator request; pregnancy; protocol deviation 
(including no longer meeting all of the inclusion criteria, or meeting 1 or more exclusion 
criteria*).
*A positive SARS-CoV-2 test result (either by NAAT or rapid antigen test) should not result 
in discontinuation of study intervention.  If study intervention has been delayed per
Section 5.5, the participant may be vaccinated once the condition(s) has/have resolved.
Note that discontinuation of study intervention does not represent withdrawal from the study.  
If study intervention is permanently discontinued, the participant will remain in the study to 
be evaluated for safety and immunogenicity.  See the SoA for data to be collected at the time 
of study intervention discontinuation and follow-up on any further evaluations that need to be 
completed.  Participants who remain in the study for evaluation of safety will be contacted by 
telephone 1 month after their last study vaccination to record AEs as described in 
Section 8.3.
In the event of study intervention discontinuation, it must be documented on the appropriate 
CRF/in the medical records whether the participant is discontinuing further receipt of study 
intervention or also from study procedures, posttreatment study follow-up, and/or future 
collection of additional information.

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7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:

Refused further study procedures;

Lost to follow-up;

Death;

Study terminated by sponsor;

AEs;

Participant request; 

Investigator request;

Protocol deviation.
If a participant does not return for a scheduled visit, every effort should be made to contact 
the participant.  All attempts to contact the participant and information received during 
contact attempts must be documented in the participant’s source document.  In any 
circumstance, every effort should be made to document participant outcome, if possible.
The investigator or his or her designee should capture the reason for withdrawal in the CRF 
for all participants.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
7.2.1. Withdrawal of Consent
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible. The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of study intervention or also from study procedures 

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and/or posttreatment study follow-up, and entered on the appropriate CRF page. In the event 
that vital status (whether the participant is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed 
in accordance with local law.
7.3. Lost to Follow-Up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to attend a required study visit:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible. Counsel the participant on the importance of maintaining the assigned visit 
schedule, and ascertain whether the participant wishes to and/or should continue in the 
study;

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
The date of birth will be collected to critically evaluate the immune response and safety 
profile by age.
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.

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Every effort should be made to ensure that protocol -required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study is approximately 
90 mL. The actual collection times of blood sampling may change. Additional blood 
samples may be taken for safety assessments at times specified by Pfizer, provided the total 
volume taken during the study does not exceed 550 mL during any period of 56 consecutive 
days.
8.1. Efficacy and/or Immunogenicity Assessments
Serum samples may be obtained for immunogenicity testing at the visits specified in the 
SoA.
The following assays will be performed: 

Full-length S-binding IgG assay.

SARS-CoV-2 neutralization assay (reference strain and,
 
).

N-binding antibody assay to establish prior serological exposure to SARS-CoV-2: to be 
performed using samples collected at Visit 1 (baseline), Visit 2 (prior to Vaccination 2), 
and Visit 3.

HAI titers to the influenza strains in the SIIV administered and H3N2-neutralizing 
antibody titers (if H3N2-HAI titers cannot be obtained) will be determined on sera 
collected at Visits 1 and 2 (prior to and 1 month [28 to 42 days] after SIIV 
administration).
Sera and plasma remaining after completion of the planned immunologic assays from blood 
draws taken throughout the study may be used for additional vaccine and infectious 
disease-related research, including exploratory immunologic assays for further 
characterization of the immune responses to BNT162b2 and/or SIIV.
CCI

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8.1.1. Biological Samples
Blood samples will be used only for scientific research. Each sample will be labeled with a 
code so that the laboratory personnel testing the samples will not know the participant’s 
identity. Samples that remain after performing assays outlined in the protocol may be stored 
by Pfizer. Unless a time limitation is required by local regulations or ethical requirements, 
the samples will be stored for up to 15 years after the end of the study and then destroyed. If 
allowed by the ICD, stored samples may be used for additional testing to better understand 
the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs. No testing of the participant’s genetic material will be performed.
The participant may request that his or her samples, if still identifiable, be destroyed at any 
time; however, any data already collected from those samples will still be used for this 
research. The biological samples may be shared with other researchers as long as 
confidentiality is maintained and no testing of the participant’s genetic material is performed.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
A clinical assessment, including medical history, will be performed on all participants at their 
first visit to establish a baseline.  Significant medical history and observations from any 
physical examination, if performed, will be documented in the CRF.
AEs and SAEs are collected, recorded, and reported as defined in Section 8.3.
Acute reactions within the first 30 minutes after administration of the study intervention will 
be assessed and documented in the AE CRF.
8.2.1. Physical Examinations
If the clinical assessment indicates that a physical examination is necessary to 
comprehensively evaluate the participant, a physical examination will be performed.
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Section 8.3.1 to Section 8.3.3.
8.2.2. Vital Signs
The participant’s oral temperature will be measured prior to each vaccination.

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8.2.3. Electronic Diary
Participants will be required to complete a reactogenicity e-diary through an application 
installed on a provisioned device or on the participant’s own personal device. All 
participants will be asked to monitor and record local reactions, systemic events, and use of 
antipyretic medication for 7 days from the day of administration of the study intervention. 
The reactogenicity e-diary allows the 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. These data do not need to be reported by the 
investigator in the CRF as AEs if reported in the e-diary.
Investigators (or designee) will be required to review the reactogenicity e-diary data online at 
frequent intervals as part of the ongoing safety review.
The investigator or designee must obtain stop dates from the participant for any ongoing 
local reactions, systemic events, or use of antipyretic medication on the last day that the 
reactogenicity e-diary was completed. The stop dates should be documented in the source 
documents and the information entered in the CRF.
8.2.3.1. Grading Scales
The grading scales used in this study to assess local reactions and systemic events as 
described below are derived from the FDA CBER guidelines on toxicity grading scales for 
healthy adult volunteers enrolled in preventive vaccine clinical trials.29
8.2.3.2. Local Reactions
During the reactogenicity e-diary reporting period, participants will be asked to assess 
redness, swelling, and pain at the BNT162b2 or saline 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 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 2. Measuring device units can be converted to 
centimeters according to the following formula: 1 measuring device unit = 0.5 cm. Pain at 
the injection site will be assessed by the participant as absent, mild, moderate, or severe 
according to the grading scale in Table 2.
If a Grade 3 local reaction is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated. Only an investigator or medically qualified person is able to classify a 

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participant’s local reaction as Grade 4. If a participant experiences a confirmed Grade 4 local 
reaction, the investigator must immediately notify the sponsor and, if it is determined to be 
related to the administration of the study intervention, further vaccinations will be 
discontinued in that participant.
Table 2.
Local Reaction Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4)a
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 qualified designee is able to classify a participant’s local reaction as Grade 4, after 
clinical evaluation of the participant or documentation from another medically qualified source 
(eg, emergency room or hospital record). Grade 4 local reactions will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Appendix 3.
8.2.3.3. Systemic Events
During the reactogenicity e-diary reporting period, participants 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 3.
If a Grade 3 systemic event is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated. Only an investigator or medically qualified person is able to classify a 
participant’s systemic event as Grade 4. If a participant experiences a confirmed Grade 4 
systemic event, the investigator must immediately notify the sponsor and, if it is determined 
to be related to the administration of the study intervention, further vaccinations will be 
discontinued in that participant.

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Table 3.
Systemic Event Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4)a
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.
a.
Only an investigator or qualified designee is able to classify a participant’s systemic event as Grade 4, 
after clinical evaluation of the participant or documentation from another medically qualified source 
(eg, emergency room or hospital record). Grade 4 systemic events will be collected on the AE case report 
form and assessed by the investigator using the AE intensity grading scale as detailed in Appendix 3.
8.2.3.4. Fever
In order to record information on fever, a thermometer will be given to participants with 
instructions on how to measure oral temperature at home.  Temperature will be collected in 
the reactogenicity e-diary 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 ≥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 4 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 

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participant’s fever as >40.0°C (>104.0°F).  If a participant experiences a confirmed fever 
>40.0°C (>104.0°F), the investigator must immediately notify the sponsor and, if it is 
determined to be related to the administration of the study intervention, further vaccinations 
will be discontinued in that participant.
Table 4.
Scale for Fever
≥38.0-38.4°C (100.4-101.1°F)
>38.4-38.9°C (101.2-102.0°F)
>38.9-40.0°C (102.1-104.0°F)
>40.0°C (>104.0°F)
8.2.3.5. Antipyretic Medication
The use of antipyretic medication to treat symptoms associated with study intervention 
administration will be recorded in the reactogenicity e-diary daily during the reporting period 
(Day 1 through Day 7).
8.2.4. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study. 
See Appendix 5 for suggested actions and follow-up assessments in the event of potential 
DILI.
See Section 8.11 for additional procedures for monitoring of potential myocarditis or 
pericarditis.
8.2.5. 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 on WOCBP at the times listed in the SoA, 
immediately before the administration of each vaccine 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 be withdrawn from administration of 
study intervention but may remain in the study.
8.3. 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.).

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The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1).
During the active collection period as described in Section 8.3.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including 
Visit 3.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form.
Investigators are not obligated to actively seek 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 he/she 
considers the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the Vaccine SAE Reporting Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the Vaccine SAE Reporting Form immediately 
upon awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.

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8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-Up of AEs and SAEs
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety.
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
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.

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An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include exposure during pregnancy, exposure during 
breastfeeding, and occupational exposure.
Any such exposure to the study intervention under study is reportable to Pfizer Safety within 
24 hours of investigator awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female participant is found to be pregnant while receiving or after discontinuing study 
intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to study 
intervention due to environmental exposure. Below are examples of environmental EDP:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by inhalation or skin contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by 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 on the Vaccine SAE Reporting Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred.  Details of the 
pregnancy will be collected after the start of study intervention and 28 days after the last 
dose of study intervention.

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
If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the Vaccine SAE Reporting Form and EDP 
Supplemental Form. Since the exposure information does not pertain to the participant 
enrolled in the study, the information is not recorded on a CRF; however, a copy of the 
completed Vaccine SAE Reporting Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs. In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the study intervention.
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if:

A female participant is found to be breastfeeding while receiving or after discontinuing 
study intervention.

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
A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental exposure 
during breastfeeding is a female family member or healthcare provider who reports that 
she is breastfeeding after having been exposed to the study intervention by inhalation or 
skin contact.
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the Vaccine SAE Reporting Form. When exposure 
during breastfeeding occurs in the setting of environmental exposure, the exposure 
information does not pertain to the participant enrolled in the study, so the information is not 
recorded on a CRF. However, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the Vaccine SAE Reporting Form, regardless 
of whether there is an associated SAE. Since the information about the occupational 
exposure does not pertain to a participant enrolled in the study, the information is not 
recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form must be 
maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
AESIs are examined as part of routine safety data review procedures throughout the clinical 
trial and as part of signal detection processes.
All AESIs must be reported as an AE or SAE following the procedures described in 
Section 8.3.1 through Section 8.3.4.  An AESI is to be recorded as an AE or SAE on the 
CRF. In addition, an AESI that is also an SAE must be reported using the Vaccine SAE 
Reporting Form.

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The following events are considered AESIs:

A confirmed diagnosis of myocarditis or pericarditis. See Section 8.11 for additional 
procedures for monitoring of potential myocarditis or pericarditis.

A confirmed COVID-19 diagnosis, or positive SARS-CoV-2 test result (by NAAT or 
rapid antigen test).
8.3.8.1. 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.
8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the Vaccine SAE 
Reporting Form to Pfizer Safety 
Within 24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant.

The administration of expired study intervention;

The administration of an incorrect study intervention;

The administration of an incorrect dosage;

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
The administration of study intervention that has undergone temperature excursion from 
the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE.
8.4. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.5. Genetics
8.5.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.6. Biomarkers
Biomarkers are not evaluated in this study.
8.7. Immunogenicity Assessments
Immunogenicity assessments are described in Section 8.1.
8.8. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.9. Study Procedures
8.9.1. Visit 1 –Vaccination 1 (Day 1)
Before enrollment and before any study-related procedures are performed, voluntary, written, 
study-specific informed consent will be obtained from the participant.  Each signature on the 
ICD must be personally dated by the signatory.  The investigator or his or her designee will 
also sign the ICD.  A copy of the signed and dated ICD must be given to the participant.  The 
source data must reflect that the informed consent was obtained before participation in the 
study.

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It is anticipated that the procedures below will be conducted in a stepwise manner.  The visit 
may be conducted across 2 consecutive days; if so, all steps from assessing the inclusion and 
exclusion criteria onwards must be conducted on the same day.

Assign a single participant number using the IRT system.

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 any medical history of clinical significance, including any history of COVID-19 
diagnosis or prior positive SARS-CoV-2 test result by NAAT or rapid antigen test.  For 
participants who are HIV-positive, record HIV viral load and CD4 count results from the 
most recent test performed in the previous 6 months.

Record previous BNT162b2 vaccine history.

Perform a clinical assessment.  If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a physical 
examination and record any findings in the source documents and, if clinically 
significant, record any findings on the medical history CRF.

Measure and record the participant’s oral temperature (°C).

Perform urine pregnancy test on WOCBP as described in Section 8.2.5.

Discuss contraceptive use as described in Section 5.3.1.

Record nonstudy vaccinations as described in Section 6.8.

Record prohibited medication as described in Section 6.8.1.

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met.

Ensure that the participant meets none of the temporary delay criteria as described in
Section 5.5.

Record AEs as described in Section 8.3.

Obtain the participant’s randomization number and study intervention container 
allocation using the IRT system.

Collect a blood sample (approximately 30 mL) for immunogenicity testing, prior to 
vaccination.

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
An unblinded site staff member will administer a single 0.3-mL injection of BNT162b2 
vaccine or saline into the left deltoid muscle.

An unblinded site staff member will administer a single 0.5-mL injection of SIIV into the 
right deltoid muscle.

Blinded site staff will observe the participant for at least 30 minutes after administration 
of BNT162b2 or saline for any reactions. Record any AEs on the CRF and on the 
Vaccine SAE Reporting Form, as applicable.

Issue the participant a measuring device to measure BNT162b2 vaccine or saline 
injection site reactions in the left deltoid muscle and a digital thermometer and provide 
instructions on their use.

Explain the e-diary technologies available for this study (see Section 8.2.3), and assist the 
participant in downloading the study application onto the participant’s own device or 
issue a provisioned device if required.

Provide instructions on reactogenicity e-diary completion and ask the participant to 
complete the reactogenicity e-diary from Day 1 through Day 7, with Day 1 being the day 
of vaccination.

Ask the participant to contact the site staff or investigator immediately if 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 BNT162b2 vaccine or saline injection site measuring 
greater than 10 cm (>20 measuring device units).

Severe pain at the BNT162b2 or saline injection site.

Any severe systemic event.

Ask the participant to contact the site staff or investigator immediately if any significant 
illness or medical event (eg, emergency room visit or hospitalization) occurs.

Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.11).

Schedule an appointment for the participant to return for the next study visit. 

Remind the participant, as appropriate, to bring the e-diary to the next visit.

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
Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the study intervention accountability records.

The investigator or appropriately qualified designee reviews the reactogenicity e-diary 
data online following vaccination to evaluate participant compliance and as part of the 
ongoing safety review.  Daily review is optimal during the active diary period.
8.9.2. Visit 2 – Vaccination 2 – 28 to 42 Days After Visit 1

Record AEs as described in Section 8.3.

Ensure and document that the participant continues to be eligible for the study 
(see Section 7 for participant discontinuation/withdrawal) and that none of the temporary 
delay criteria are met.

Record nonstudy vaccinations as described in Section 6.8.

Record prohibited medication as described in Section 6.8.1.

Perform urine pregnancy test on WOCBP as described in Section 8.2.5.

Discuss contraceptive use as described in Section 5.3.1.

Review the participant’s e-diary data. Collect stop dates of any e-diary events (local 
reactions or systemic events) ongoing on the last day that the reactogenicity e-diary was 
completed and record stop dates in the CRF.

Measure and record the participant’s oral temperature (°C).

Obtain the participant’s study intervention container allocation using the IRT system.

Collect a blood sample of approximately 30 mL for immunogenicity assessments prior to 
vaccination.

An unblinded site staff member will administer a single 0.3-mL injection of the 
BNT162b2 or saline into the left deltoid muscle.

Blinded site staff will observe the participant for at least 30 minutes after administration 
of the BNT162b2 or saline for any reactions. Record any AEs on the CRF and on the 
Vaccine SAE Reporting Form, as applicable.

Confirm that the e-diary is working and review instructions, if necessary. Ask the 
participant to complete the reactogenicity e-diary from Day 1 through Day 7, with Day 1 
being the day of vaccination. Provide thermometer or measuring device, if needed.

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
Ask the participant to contact the site staff or investigator immediately if the participant 
experiences any of the following from Day 1 through Day 7 after vaccination (where 
Day 1 is the day of vaccination) to determine if an unscheduled reactogenicity visit is 
required: 

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the BNT162b2 or saline injection site measuring greater than 
10 cm (>20 measuring device units).

Severe pain at the BNT162b2 or saline injection site.

Any severe systemic event.

Ask the participant to contact the site staff or investigator immediately if any significant 
illness or medical event (eg, emergency room visit or hospitalization) occurs.

Ask the participant to contact the site staff or investigator if the participant experiences 
acute chest pain, shortness of breath, or palpitations (see Section 8.11).

Schedule an appointment for the participant to return for the next study visit.

Remind the participant, as appropriate, to bring the e-diary to the next visit.

Complete the source documents.

The investigator or an authorized designee completes the CRFs and an unblinded 
dispenser/administrator updates the study intervention accountability records.

The investigator or appropriately qualified designee reviews the reactogenicity e-diary 
data online following vaccination to evaluate participant compliance and as part of the 
ongoing safety review.  Daily review is optimal during the active diary period.
8.9.3. Visit 3 – (Follow-Up After Vaccination 2 – 28 to 42 Days After Vaccination 2)

Record AEs as described in Section 8.3.

Review the participant’s reactogenicity e-diary data.  Collect stop dates of any 
reactogenicity e-diary events ongoing on the last day that the reactogenicity e-diary was 
completed and record stop dates in the CRF if required.

Record nonstudy vaccinations as described in Section 6.8.

Record prohibited medication as described in Section 6.8.1.

Discuss contraceptive use as described in Section 5.3.1.

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
For participants who are HIV-positive, record HIV viral load and CD4 count results from 
the most recent test performed since Visit 2 (if any).

Collect a blood sample (approximately 30 mL) for immunogenicity testing.

Collect e-diary or assist the participant with deleting the application.

Ask the participant to contact the site staff or investigator if a medically attended event 
(eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.10. Unscheduled Visit for a Grade 3 or Suspected Grade 4 Reaction
If a Grade 3 local reaction (Section 8.2.3.2), systemic event (Section 8.2.3.3), or fever 
Section 8.2.3.4) 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 8.2.3.2), systemic event (Section 8.2.3.3), or fever 
(Section 8.2.3.4) 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 classification.
A site visit must be scheduled as soon as possible to assess the participant unless any of the 
following is true:

The participant is unable to attend the unscheduled visit.

The local reaction/systemic event is no longer present at the time of the telephone 
contact.

The participant recorded an incorrect value in the reactogenicity e-diary (confirmation of 
a reactogenicity e-diary data entry error).

The PI or authorized designee determined it was not needed.
This telephone contact will be recorded in the participant’s source documentation and the 
CRF.
If the participant is unable to attend the unscheduled visit, or the PI or authorized designee 
determined it was not needed, any ongoing local reactions/systemic events must be assessed 
at the next study visit.
During the unscheduled visit, the reactions should be assessed by the investigator or a 
medically qualified member of the study staff, such as a study physician or a study nurse, as 
applicable to the investigator’s local practice, who will:

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
Measure oral temperature (°C).

Measure minimum and maximum diameters of redness (if present).

Measure minimum and maximum diameters of swelling (if present).

Assess injection site pain (if present) in accordance with the grades provided in
Section 8.2.3.2.

Assess systemic events (if present) in accordance with the grades provided in
Section 8.2.3.3.

Assess for other findings associated with the reaction and record on the AE page of the 
CRF, if appropriate.

The investigator or an authorized designee will complete the unscheduled visit 
assessment page of the CRF.
8.11. 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 within 4 weeks after 
a study vaccination should be specifically evaluated, preferably by a cardiologist, for possible 
myocarditis or pericarditis.
In addition to a clinical evaluation, the following should be performed:

ECG and

Measurement of the troponin level
If myocarditis or pericarditis is suspected based upon the initial evaluation, the following 
should also be performed:

Cardiac echocardiogram and/or

Cardiac magnetic resonance study
Details of the symptoms reported, and results of the investigations performed, will be 
recorded in the CRF.
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in a SAP, which will be maintained by the sponsor.  The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.

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9.1. Statistical Hypotheses
9.1.1. Statistical Hypothesis 
9.1.1.1. Statistical Hypothesis for BNT162b2
The primary immunogenicity objective on immune response elicited by BNT162b2 will be 
evaluated by the following hypothesis:
H01: ln(μA) – ln(μB) ≤ ln(0.67)  
where ln(0.67) corresponds to a 1.5-fold margin for noninferiority, and ln(µA) and ln(µB) are 
the natural log of the geometric mean of full-length S-binding IgG levels 1 month after 
vaccination with BNT162b2 for the coadministration group and the separate-administration 
group, respectively. Noninferiority will be declared if the lower limit of the 2-sided 95% CI 
for the GMR (coadministration group to separate-administration group) is >0.67.
9.1.1.2. Statistical Hypothesis for SIIV
The primary immunogenicity objective on immune response elicited by SIIV will be 
evaluated by the following hypothesis:
H02: ln(μC) – ln(μD) ≤ ln(0.67)  
where ln(0.67) corresponds to a 1.5-fold margin for noninferiority, and ln(µC) and ln(µD) are 
the natural log of the geometric mean of the strain-specific HAI titers (or H3N2-neutralizing 
antibody titers if H3N2-HAI titers cannot be obtained) 1 month after vaccination with SIIV 
for the coadministration group and the separate-administration group, respectively. 
Noninferiority will be declared for an influenza strain if the lower limit of the 2-sided 95% 
CI for the GMR (coadministration group to separate-administration group) is >0.67. The 
primary SIIV immunogenicity objective of the study will be achieved if the noninferiority is 
met for each of the influenza strains.
9.1.2. Estimands
The estimands corresponding to each primary, secondary, and exploratory objective are 
described in the table in Section 3.
The estimands to evaluate the immunogenicity objectives will be based on the evaluable 
immunogenicity population (Section 9.2).  These estimands estimate the vaccine effect in the 
hypothetical settings where participants follow the study schedules and protocol requirements 
as directed. The estimands address the objective of estimating the maximum potential 
difference between 2 vaccine groups of the target population, since the impact of 
noncompliance is likely to diminish the observed difference between the 2 compared groups. 
Missing serology 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.

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In the primary safety objective evaluations, missing reactogenicity e-diary data will not be 
imputed. Missing AE start dates will be imputed according to Pfizer safety rules.  No other 
missing information will be imputed in the safety analysis.
9.1.3. Multiplicity Adjustment
For the primary immunogenicity assessment of noninferiority of coadministration of 
BNT162b2 and SIIV to administration of SIIV followed by BNT162b2 1 month later, the 
hypotheses for the full-length S-binding IgG levels and for all the influenza strains in SIIV 
will be tested at a 1-sided alpha level of 0.025.
The primary immunogenicity objectives of the study will be achieved if noninferiority is met 
for the full-length S-binding IgG levels and for each of the influenza strains.  Therefore, the 
type I error rate for the immunogenicity assessments is well controlled.
9.2. Analysis Sets
For the purposes of analysis, the following analysis sets are defined:
Enrolled
All participants who have a signed ICD.
Randomized 
All participants who are assigned a randomization number in 
the IRT system.
Evaluable BNT162b2
immunogenicity
All eligible randomized participants who receive all 
vaccinations at Visit 1 as randomized (coadministration group) 
or receive all vaccinations at Visit 1 and Visit 2 as randomized 
(separate-administration group), have at least 1 valid and 
determinate full-length S-binding IgG or 
SARS-CoV-2–neutralizing titer result from the blood sample 
collected within an appropriate window at Visit 2
(coadministration group) or at Visit 3 (separate-administration 
group), and have no other important protocol deviations as 
determined by the clinician.
Evaluable SIIV 
immunogenicity
All eligible randomized participants who receive all 
vaccinations at Visit 1 as randomized, have at least 1 valid and 
determinate HAI titer or H3N2-neutralizing antibody titer 
result from the blood sample collected within an appropriate 
window at Visit 2, and have no other important protocol 
deviations as determined by the clinician.
All-available 
immunogenicity
All randomized participants who have at least 1 valid and 
determinate immunogenicity result after receiving the study 
intervention.
Safety
All participants who receive any of the study intervention.

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9.3. Statistical Analyses
The SAP will be developed and finalized before database lock for any of the planned 
analyses in Section 9.4. It 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 populations.  Participants will be summarized by 
vaccine group according to the study intervention they actually received.  Missing 
reactogenicity e-diary data will not be imputed; missing AE start dates will be handled 
according to the Pfizer safety rules.
For all the immunogenicity endpoints, the analysis will be based on the evaluable 
immunogenicity populations.  An additional analysis may be performed based on the 
all-available immunogenicity 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.  Missing serology data will not be imputed.
9.3.1.1. Analysis for Binary Data
Descriptive statistics for categorical variables (eg, proportions) are the percentage (%), the 
numerator (n) and the denominator (N) used in the percentage calculation, and the 2-sided 
95% CIs where applicable.
The exact 95% CI for binary endpoints for each group will be computed using the 
F distribution (Clopper-Pearson).30 The 95% CI for the between-group difference for binary 
endpoints will be calculated using the Miettinen and Nurminen method.31
3-Tier Approach for AE Summary
AEs will be categorized according to MedDRA terms. A 3-tier approach will be used to 
summarize AEs.  Under this approach, AEs are classified into 1 of 3 tiers: 
1. Tier 1 events are prespecified events of clinical importance and are identified in a list in 
the product’s safety review plan; there is no Tier 1 event identified for BNT162b2 at this 
stage.
2. Tier 2 events are those that are not Tier 1 but are considered “relatively common”; 
a MedDRA preferred term is defined as a Tier 2 event if there are at least 1% of 
participants in at least 1 vaccine group reporting the event; 
3. Tier 3 events are those that are neither Tier 1 nor Tier 2 events.

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The 3-tier approach will be used to summarize AEs.  For both Tier 1 (if any are identified 
during the study) and Tier 2 events, the 95% CI for the between-group difference in 
proportions will be calculated based on the Miettinen and Nurminen method.  In addition, for 
Tier 1 events (if any), the asymptotic p-values will also be presented for the difference in 
proportions, based on the same test statistic and under the assumption that the test statistic is 
asymptotically normally distributed.  For Tier 3 events, descriptive summary statistics for 
each vaccine group will be provided.
9.3.1.2. Analysis for Continuous Data
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
standard deviation, minimum, and maximum.
9.3.1.2.1. Geometric Mean Ratios
Model-Based
As the primary approach, the GMRs and associated 95% CIs will be calculated by 
exponentiating the difference in LS means of the 2 vaccine groups and the corresponding CIs 
based on analysis of logarithmically transformed assay results using a linear regression 
model with vaccine group, age group, and evidence of SARS-CoV-2 infection (through 
1 month after BNT162b2 vaccination [yes or no]) as factors.
Unadjusted
The GMRs will be calculated as the difference in the means of logarithmically transformed 
assay results for the 2 groups and exponentiating the difference.  The associated 2-sided 95% 
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.
9.3.1.2.2. Geometric Mean Fold Rises
GMFRs are defined as ratios of the results after vaccination to the results before vaccination.  
GMFRs are limited to participants with nonmissing values at both time points.
GMFRs will be calculated as the mean of the difference of logarithmically transformed assay 
results (later time point minus earlier time point) and exponentiating the mean.  The 
associated 2-sided 95% CIs will be obtained by constructing CIs using Student’s 
t-distribution for the mean difference on the logarithm scale and exponentiating the 
confidence limits.
9.3.1.2.3. 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.

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9.3.1.2.4. Reverse Cumulative Distribution Curves
Empirical RCDCs will plot proportions of participants with values equal to or exceeding a 
specified assay value versus the indicated assay value, for all observed assay values.  Data 
points will be joined by a step function with data points on the left side of the step.
9.3.2. Primary Endpoint(s)/Estimand(s) Analysis
Endpoint
Statistical Analysis Methods
BNT162b2 
immunogenicity
GMR of full-length S-binding IgG levels 1 month after vaccination 
with BNT162b2 (at Visit 1) in the coadministration group to the 
IgG levels 1 month after vaccination with BNT162b2 (at Visit 2) in 
the separate-administration group
GMR and the associated 2-sided 95% CIs will be calculated using the 
statistical methods described in Section 9.3.1.2.1.
Noninferiority will be declared if the lower bound of the 2-sided 95% 
CI for the GMR is greater than 0.67.
As the primary approach for the noninferiority assessment, a linear 
regression model that includes vaccine group, age group, and evidence 
of SARS-CoV-2 infection (through 1 month after BNT162b2 
vaccination) will be used to calculate the adjusted GMR and 2-sided 
95% CI.  The unadjusted GMR and CI will also be calculated.
SIIV 
immunogenicity
GMR of the strain-specific HAI (or H3N2-neutralizing antibody) 
titers 1 month after vaccination with SIIV in the coadministration 
group to the corresponding HAI (or H3N2-neutralizing antibody) 
titers in the separate-administration group
For each influenza strain, GMR and the associated 2-sided 95% CIs 
will be calculated using the statistical methods described in 
Section 9.3.1.2.1.
Noninferiority for a strain will be declared if the lower bound of the 
2-sided 95% CI for the GMR is greater than 0.67. The primary SIIV 
immunogenicity objective of the study will be achieved if the 
noninferiority is met for each of the influenza strains.
As the primary approach for the noninferiority assessment, a linear 
regression model that includes vaccine group, age group, and evidence 
of SARS-CoV-2 infection (through 1 month after BNT162b2 
vaccination) will be used to calculate the adjusted GMR and 2 sided 
95% CI.  The unadjusted GMR and CI will also be calculated.

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Endpoint
Statistical Analysis Methods
Safety
Descriptive statistics will be provided for each reactogenicity endpoint 
for each vaccine group.  Local reactions and systemic events from 
Day 1 through Day 7 after each vaccination (where Day 1 is the day of 
vaccination) will be presented by severity and cumulatively across 
severity levels. Descriptive summary statistics will include counts and 
percentages of participants with the indicated endpoint and the 
associated Clopper-Pearson 95% CIs (see Section 9.3.1.1).
AEs will be categorized according to MedDRA terms.  Counts, 
percentages, and the associated Clopper-Pearson 95% CIs of AEs 
within 1 month after each vaccination will be provided for each vaccine 
group. A 3-tier approach will be used to summarize AEs as described 
in Section 9.3.1.1. There is no Tier 1 event identified for BNT162b2 at 
this stage. For Tier 2 AEs, the between-group difference and 95% CIs 
will be calculated for 1 month after vaccination with SIIV and 
BNT162b2 at Visit 1 for the coadministration group vs 1 month after 
vaccination with SIIV and saline at Visit 1 for the 
separate-administration group, and for 1 month after vaccination with 
SIIV and BNT162b2 at Visit 1 for the coadministration group vs 
1 month after vaccination with BNT162b2 at Visit 2 for the 
separate-administration group.
SAEs will be categorized according to MedDRA terms.  Counts, 
percentages, and the associated Clopper-Pearson 95% CIs of SAEs 
from the first vaccination to 1 month after the last vaccination will be 
provided for each vaccine group.
9.3.3. Secondary Endpoint(s)/Estimand(s) Analysis
Endpoint
Statistical Analysis Methods
BNT162b2 
immunogenicity
GMCs/GMTs of full-length S-binding IgG levels and 
SARS-CoV-2–neutralizing titers
GMCs/GMTs and associated 2-sided 95% CIs at before vaccination 
and 1 month after vaccination with BNT162b2 will be provided for 
each vaccine group using the statistical methods described in 
Section 9.3.1.2.3.
GMFR of full-length S-binding IgG levels and 
SARS-CoV-2–neutralizing titers from before vaccination to 1 
month after vaccination with BNT162b2

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Endpoint
Statistical Analysis Methods
GMFR and the associated 2-sided 95% CIs will be provided for each 
vaccine group using the statistical methods described in
Section 9.3.1.2.2.
SIIV 
immunogenicity
GMTs of the strain-specific HAI titers and H3N2-neutralizing 
antibody titers
For each influenza strain, GMTs and the associated 2-sided 95% CIs 
at before vaccination and 1 month after vaccination with SIIV will be 
calculated for each vaccine group.
GMFR of the strain-specific HAI titers and H3N2-neutralizing 
antibody titers from before vaccination to 1 month after 
vaccination with SIIV
For each influenza strain, GMFR and the associated 2-sided 95% CIs 
will be calculated for each vaccine group.
9.3.4. Tertiary/Exploratory Endpoint(s)
Endpoint
Statistical Analysis Methods
SIIV 
immunogenicity
Percentage of participants with strain-specific HAI titers ≥1:40 
1 month after vaccination with SIIV
For each influenza strain, counts, percentages, and the associated 
Clopper-Pearson 95% CIs of participants with strain-specific HAI 
titers ≥1:40 1 month after vaccination with SIIV will be provided for 
each vaccine group.
Percentage of participants with strain-specific HAI seroconversion 
1 month after vaccination with SIIV
Seroconversion is defined as:

an HAI titer <1:10 before SIIV vaccination and an HAI titer 
≥1:40 1 month after SIIV vaccination or 

an HAI titer ≥1:10 before vaccination and a minimum 4-fold 
rise in HAI titer 1 month after SIIV vaccination. 
For each influenza strain, counts and percentages of participants with 
strain-specific HAI titer seroconversion 1 month after vaccination with 
SIIV will be provided for each vaccine group. The associated 
Clopper-Pearson 95% CIs will also be provided.

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Endpoint
Statistical Analysis Methods
Percentage of participants with H3N2 neutralization
seroprotection 1 month after vaccination with SIIV
Percentage of participants with H3N2 neutralization 
seroconversion 1 month after vaccination with SIIV
The definitions of H3N2 neutralization seroprotection and 
seroconversion will be described in the SAP when H3N2 
neutralization assay information becomes available. Counts and
percentages of participants with H3N2 neutralization seroprotection
and seroconversion 1 month after vaccination with SIIV will be 
provided for each vaccine group.  The associated Clopper-Pearson 
95% CIs will also be provided.
9.4. Interim Analyses
No formal interim analysis will be conducted for this study.  Only 1 analysis will be 
performed at the completion of the study.
9.5. Sample Size Determination
The sample size calculation is based on the primary efficacy estimands and corresponding 
endpoints: full-length S-binding IgG levels and strain-specific HAI titers. Table 5 presents 
the power to demonstrate noninferiority of the immune responses elicited by BNT162b2 and 
SIIV from the coadministration group to the separate-administration group. If the GMR of 
the coadministration group to the separate-administration group is 0.9 for SARS-CoV-2 
full-length S-binding IgG and each influenza strain, with assumed standard deviations for 
each endpoint, a sample size of 450 evaluable participants per group will provide an overall 
power of 90.7% to declare noninferiority for all coprimary endpoints. Assuming a 
nonevaluable rate of 20%, the study will randomize approximately 1126 participants to 
achieve 450 evaluable participants in each group.

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Table 5.
Power Calculations for NI of the Coadministration Group to the 
Separate-Administration Group in SARS-CoV-2 Full-Length S-Binding 
IgG Levels and HAI Titers
Endpoint
NI Margin
SD in Natural Log
Scalea
Power 
Assumed GMR=0.9
N=450 Evaluable/Group
SARS-CoV-2 full-length 
S-binding IgG
1.5-fold
1.05
98.8%
HAI titers
A/H1N1
1.5-fold
1.05
98.8%
A/H3N2
1.5-fold
1.07
98.5%
B/Brisbane
1.5-fold
1.13
97.4%
B/Massachusetts
1.5-fold
1.16
96.8%
Allb
90.7%
Abbreviations: GMR = geometric mean ratio; HAI = hemagglutination inhibition assay; 
IgG = immunoglobulin G; NI = noninferiority; S-binding = spike protein–binding; 
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
a.
Assay SDs for SARS-CoV-2 full-length S-binding IgG were based on the 1-month post–Dose 2 
immunogenicity results from the C4591020 study (18-55 years of age), and the C4591001 study, Phase 2, 
in the 56-85-year age group; assay SDs for HAI endpoints were based on results on Afluria Quad.32
b.
“All” = product of each power.

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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 536/2014 for clinical 
studies (if applicable), European Medical Device Regulation 2017/745 for clinical device 
research (if applicable), and all other applicable local regulations.

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10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant and answer all questions regarding the study. The 
participant should be given sufficient time and opportunity to ask questions and to decide 
whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.

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The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the IRB/EC-approved ICD(s) 
during their participation in the study as required per local regulations.
A copy of the ICD(s) must be provided to the participant. Participants who are rescreened 
are required to sign a new ICD.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password-protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record ID. In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee 
This study will use a DMC. The DMC is independent of the study team and includes only 
external members who will review cumulative unblinded data throughout the study. The 
DMC charter describes the role of the DMC in more detail.
The DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter. The recommendations made by the DMC 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, investigators, as appropriate. 

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10.1.6. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.

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Data sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.7. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
QTLs are predefined parameters that are monitored during the study. Important deviations 
from the QTLs and any remedial actions taken will be summarized in the clinical study 
report.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.

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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 retain 
notification in relation to the study. Furthermore, the investigator will cooperate with the 
sponsor or its agents to prepare the investigator site for the inspection and will allow the 
sponsor or its agent, whenever feasible, to be present during the inspection. The investigator 
site and investigator will promptly resolve any discrepancies that are identified between the 
study data and the participant's medical records. The investigator will promptly provide 
copies of the inspection findings to the sponsor or its agent. Before response submission to 
the regulatory authorities, the investigator will provide the sponsor or its agents with an 
opportunity to review and comment on responses to any such findings.
10.1.8. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes source data and its origin can be found in the study monitoring 
plan, which is maintained by the sponsor.
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.

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10.1.9. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/EC 
or local health authorities, the sponsor's procedures, or the ICH GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.10. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications,
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 

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intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.11. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study 
documentation/study portal or other electronic system. 
To facilitate access to appropriately qualified medical personnel for study-related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 
the time of informed consent. The ECC contains, at a minimum, (a) protocol and study 
intervention identifiers, (b) participant’s study identification number, (c) site emergency 
phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center number.
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. The Pfizer Call Center number should only be 
used when the investigator and site staff cannot be reached. The Pfizer Call Center number is 
not intended for use by the participant directly; if a participant calls that number directly, he 
or she will be directed back to the investigator site.

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10.2. Appendix 2: Clinical Laboratory Tests
A pregnancy test will be performed at times defined in the SoA section of this protocol: Visit 
1 (Vaccination 1/Day 1) and Visit 2 (Vaccination 2/28 to 42 days after Vaccination 1).

Pregnancy test (-hCG): Local urine testing will be standard for the protocol unless
serum testing is required by local regulation or IRB/EC for female participants of
childbearing potential.
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 either an 
increase in frequency and/or intensity of the condition.

New condition detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE or SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.

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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of an SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event 
that hypothetically might have caused death if it were more severe.

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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.
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 non-pathogenic, is considered serious
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.

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g. Other situations:

Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
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 on the Vaccine SAE Reporting Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; 
(2) nonserious AEs; and (3) exposure to the study intervention under study during 
pregnancy or breastfeeding, and occupational exposure. 
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF. When the same data are collected, the forms 
must be completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None

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Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding.
All AEs or SAEs 
associated with exposure 
during pregnancy or 
breastfeeding.
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not 
captured in the CRF.
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE).*
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE).**
Environmental or 
occupational exposure to 
the product under study to 
a non-participant (not 
involving EDP or EDB).
None.  Exposure to a study 
non-participant is not 
collected on the CRF.
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported.***
*
EDP (with or without an associated AE or SAE): any pregnancy information is reported to Pfizer 
Safety using Vaccine SAE Reporting Form and EDP Supplemental Form; if the EDP is associated 
with an SAE, then the SAE is reported to Pfizer Safety using the Vaccine SAE Reporting Form. 
** EDB is reported to Pfizer Safety using the Vaccine SAE Reporting Form which would also 
include details of any SAE that might be associated with the EDB. 
*** Environmental or Occupational exposure: AEs or SAEs associated with occupational exposure are 
reported to Pfizer Safety using the Vaccine SAE Reporting Form. 

When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE or SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the Vaccine SAE 
Reporting Form/AE or SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE or SAE.

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Assessment of Intensity
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.
GRADE 
If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING to 
describe the maximum intensity of the AE. For purposes of consistency, 
these intensity grades are defined as follows:
1
MILD
Does not interfere with participant's usual 
function.
2
MODERATE
Interferes to some extent with participant's usual 
function.
3
SEVERE
Interferes significantly with participant's usual 
function.
4
LIFE-THREATENING
Life-threatening consequences; urgent 
intervention indicated.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE or SAE. The investigator will use clinical 
judgment to determine the relationship.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE or SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE or SAE and has provided an assessment of causality.

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
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor. In addition, if the investigator determines that 
an SAE is associated with study procedures, the investigator must record this 
causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements.
Follow-Up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the 
sponsor, to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally submitted 
documents.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.

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10.3.4. 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.

If the electronic system is unavailable, then the site will use the paper SAE DCT 
(see next section) to report the event within 24 hours.

The site will enter the SAE data into the electronic DCT (eg, eSAE or PSSA) or 
paper form (as applicable) as soon as the data become available.

After the study is completed at a given site, the electronic DCT will be taken 
off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic DCT has been taken off-line, 
then the site can report this information on a paper SAE form (see next section) or 
to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form

Facsimile transmission of the Vaccine SAE Reporting Form is the preferred 
method to transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames.

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10.4. 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 when having sexual intercourse with a woman of 
childbearing potential 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 using an acceptable contraceptive method as described below 
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. 
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).

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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 an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. In addition:

A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 

A female on HRT and whose menopausal status is in doubt will be required to use 
one of the nonestrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment.
10.4.4. 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:
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.

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3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion (eg, bilateral tubal ligation).
5. Vasectomized partner:

A 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.
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.
8. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.
9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.
10. Male or female condom with or without spermicide.
11. Cervical cap, diaphragm, or sponge with spermicide.
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).

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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
LFTs are not required as a routine safety monitoring procedure in this study. However, 
should an investigator deem it necessary to assess LFTs because a participant presents with 
clinical signs/symptoms, such LFT results should be managed and followed as described 
below.
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks. The increase in TBili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be 
elevated within the same laboratory sample). In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased. This occurrence is still regarded as a 
potential DILI. Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

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
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected Hy’s law
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.

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10.6. Appendix 6: Alternative Measures During Public Emergencies
10.6.1. Telehealth Visits
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the Schedule of 
Activities or unscheduled visits. Telehealth visits may be used to continue to assess 
participant safety and collect data points. Telehealth includes the exchange of healthcare 
information and services via telecommunication technologies (eg, audio, video, 
video-conferencing software) remotely, allowing the participant and the investigator to 
communicate on aspects of clinical care, including medical advice, reminders, education, and 
safety monitoring. The following assessments must be performed during a telehealth visit:

Review and record any AEs and SAEs since the last contact. Refer to Section 8.3.

Record nonstudy vaccinations as described in Section 6.8. Review and record 
contraceptive method if applicable. Confirm that the participant is adhering to the 
contraception method(s) required in the protocol. Refer to Section 5.3.1.
Study participants must be reminded to promptly notify site staff about any change in their 
health status.

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10.7. Appendix 7: Criteria for Allowing Inclusion of Participants With Chronic Stable 
HIV, HCV, or HBV Infection
Potential participants with chronic stable HIV, HCV, or HBV infection may be considered 
for inclusion if they fulfill the following respective criteria.
Known HIV infection

Confirmed stable HIV disease, defined as documented viral load <50 copies/mL and CD4 
count >200 cells/mm3 within 6 months before enrollment, and on stable antiretroviral 
therapy for at least 6 months.
Known HCV infection

History of chronic HCV with evidence of sustained virological response, defined as 
undetectable HCV RNA, for ≥12 weeks following HCV treatment or without evidence of 
HCV RNA viremia (undetectable HCV viral load).
Known HBV infection
Confirmed inactive chronic HBV infection, defined as HBsAg present for ≥6 months and the 
following:

HBeAg negative, anti-HBe positive

Serum HBV DNA <2000 IU/mL

Persistently normal ALT and/or AST levels
In those who have had a liver biopsy performed, findings that confirm the absence of 
significant necroinflammation.

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10.8. Appendix 8: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the table of contents (TOC).  The protocol amendment summary of changes 
tables for past amendment(s) can be found below:
Amendment 1 (22 December 2021)
Overall Rationale for the Amendment: The BNT162b2 booster rollout in southern 
hemisphere countries will significantly reduce the pool of potential study participants ≥65 
years of age because the majority will be due to receive their BNT162b2 booster prior to 
study start. The age eligibility of this study has been modified to include a younger age 
group who will be eligible for the booster vaccination during the planned study recruitment 
period. 
 
Section # and Name
Description of Change
Brief Rationale
Study title, Section 1.1 (Synopsis), 
Section 2.1 (Study Rationale), 
Section 4.1 (Overall Design), 
Section 5.1 (Inclusion Criteria)
Updated age eligibility to 
include adults 18 through 
64 years of age (stratified 
by age group [18-49 years 
and 50-64 years] and the 
removed ≥65-year age 
group.
Updated to mitigate 
risk to the achieving 
recruitment target.
Section 9 (Statistical Considerations)
Updated sample size 
calculations with new 
assumptions on assay SDs 
in Table 5.  An additional 
reference (19) was added 
for assay SDs of HAI 
endpoints based on Afluria 
Quad.
Modified to reflect 
younger age group 
and comparator 
SIIV.
Added a linear regression 
model to calculate GMR for 
the primary 
immunogenicity endpoints. 
Updated to 
accommodate added 
stratifications (age 
and timing of the 
second dose of 
BNT162b2 prior to 
Visit 1) in the 
randomization of the 
study design.
Revised the names of 
immunogenicity 
populations. 
Updated to match 
the wording of the 
objectives.
CCI

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Section # and Name
Description of Change
Brief Rationale
Section 1.2 (Schema), Section 5.1
(Inclusion Criteria)
Updated eligibility criteria 
to include participants who 
have received their second 
dose of 30 µg BNT162b2 
90 to 365 days before Visit 
1 (Day 1). 
Updated to 
accommodate 
potential shorter 
booster intervals 
because of emerging 
VOCs.
Section 1 (Protocol Summary), 
Section 3 (Objectives, Estimands, and 
Endpoints), Section 4.1 (Overall 
Design), Section 8 (Study Assessments 
and Procedures), Section 8.5.2 
(Retained Research Samples for 
Genetics), Section 8.9.2 (Visit 2 – 1-
Week Follow-Up Visit), Section 8.9.4 
(Visit 4 – 1-Week Follow-Up Visit),
Section 9 (Statistical Considerations), 
Section 10.5 (Appendix 5: Genetics)
 
Removed for 
operational reasons.
Section 1.3 (SoA), Section 5.2
(Exclusion Criteria), Section 6.8.2
(Permitted During the Study), Section 8
(Study Assessments and Procedures), 
Section 10.2 (Clinical Laboratory Tests)
Added pregnancy test for 
WOCBP and updated 
eligibility criteria to 
exclude women who are 
pregnant or breastfeeding.
Updated 
requirements due to 
younger age group.
CCI

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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
2019-nCoV
novel coronavirus 2019
AE
adverse event
AESI
adverse event of special interest
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BCR
B-cell receptor
CBER
Center for Biologics Evaluation and Research
CDC
Centers for Disease Control and Prevention
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CONSORT
Consolidated Standards of Reporting Trials
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
DCT
data collection tool
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram
eCRF
electronic case report form
e-diary
electronic diary
EDB
exposure during breastfeeding
EDP
exposure during pregnancy
EMA
European Medicines Agency
eSAE
electronic serious adverse event
EU
European Union
EUA
emergency use authorization
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMC
geometric mean concentration
GMFR
geometric mean fold rise

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Abbreviation
Term
GMR
geometric mean ratio
GMT
geometric mean titer
HAI
hemagglutination inhibition
HBe
hepatitis B e
HBeAg
hepatitis B e antigen
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IgG
immunoglobulin G
IMP
investigational medicinal product
IND
investigational new drug
INR
international normalized ratio
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IRB
institutional review board
IRT
interactive response technology
IV
intravenous(ly)
IWR
interactive Web-based response
LFT
liver function test
LLOQ
lower limit of quantitation
LNP
lipid nanoparticle
MedDRA
Medical Dictionary for Regulatory Activities
MHRA
Medicines and Healthcare Products Regulatory Agency
modRNA
nucleoside-modified messenger ribonucleic acid
mRNA
messenger ribonucleic acid
N/A
not applicable
NAAT
nucleic acid amplification test 
N-binding
SARS-CoV-2 nucleoprotein–binding
NI
noninferiority
NIMP
noninvestigational medicinal product
P2 S
SARS-CoV-2 full-length, P2 mutant, prefusion spike glycoprotein
PI
principal investigator
PPE
personal protective equipment
PSSA
Pfizer’s Serious Adverse Event Submission Assistant
PT
prothrombin time
QTL
quality tolerance limit
CCI

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Abbreviation
Term
RCDC
reverse cumulative distribution curve
RNA
ribonucleic acid
RSV
respiratory syncytial virus
S
spike protein
S1
spike protein S1 subunit
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SIIV
seasonal inactivated influenza vaccine
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
TCR
T-cell receptor
Th1
T-helper type 1
TOC
table of contents
UK
United Kingdom
ULN
upper limit of normal
US
United States
VAED
vaccine-associated enhanced disease
VE
vaccine efficacy
VOC
variant of concern
WHO
World Health Organization
WOCBP
woman/women of childbearing potential

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine) 
Protocol C4591030
Final Protocol Amendment 2, 09 March 2022
Page 100
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Protocol C4591030
Final Protocol Amendment 2, 09 March 2022
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Protocol C4591030
Final Protocol Amendment 2, 09 March 2022
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Final Protocol Amendment 2, 09 March 2022
Page 103
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