A PHASE 3, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF MULTIPLE FORMULATIONS OF THE VACCINE CANDIDATE BNT162B2 AGAINST COVID 19 IN HEALTHY ADULTS 18 THROUGH 55 YEARS OF AGE
Phase: PHASE3
Conditions: SARS-CoV-2 Infection, COVID-19
Sponsor: BioNTech SE

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
Page 1
A PHASE 3, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE 
SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF MULTIPLE
FORMULATIONS OF THE VACCINE CANDIDATE BNT162b2 AGAINST 
COVID-19 IN HEALTHY ADULTS 18 THROUGH 55 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:
19736
EudraCT Number:
2020-002641-42
ClinicalTrials.gov ID:
NCT04816669
Protocol Number:
C4591020
Phase:
3
Short Title: A Phase 3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of 
Multiple Formulations of BNT162b2 Against COVID-19 in Healthy Adults
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promptly notified.

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Protocol amendment 
2
13 Sep 2021

The primary immunogenicity analysis
demonstrated that the immune response 
elicited by the lyophilized formulation did 
not meet the noninferiority criteria 
compared to the frozen-liquid formulation 
of BNT162b2. As a result, for the benefit 
of participants, updates were made to 
offer and administer an additional vaccine 
dose, using the frozen-liquid formulation,
to participants who originally received 
2 doses of the lyophilized formulation of 
BNT162b2.

Exploratory estimand relating to 
lyophilized formulation have been 
reported (GMRs of RTU formulation to 
lyophilized formulation in SDVs 1 month 
after Dose 2)

Added 2 exploratory objectives
corresponding to administration of Dose 3 
and updated the pertinent details for the 
statistical analysis.

Updated Section 9.4.4 to add an 
exploratory immunogenicity objective, 
and clarified that IgG data from all 
participants in Part 1 will be used and
neutralizing titer data from a random 
sample of ~30 age-matched participants in 
Part 1 receiving frozen-liquid BNT162b2 
in MDVs will be used.

Following updates were in specified 
sections in response to commitment made 
to CBER concerning myocarditis and 
pericarditis:
o
Updated Section 2.3.1
(Risk Assessment) to address 
myocarditis and pericarditis safety 
concerns.
o
Added Section 8.13 for 
requirement of unplanned visit to 
capture data pertaining to 
myocarditis and pericarditis.

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
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Protocol amendment 
1
15 Apr 2021

Removed all references to lyophilized
MDV and added ability to assess
frozen-liquid BNT162b2 with LNP size at 
the upper end of specification and RTU
BNT162b2 in a second part of the study.

Updated corresponding objectives, 
estimands, and endpoints, including 
removal of 1 Primary Immunogenicity 
objective and addition of 2 new 
Exploratory objectives in line with 
changes to formulation evaluation. 
Section 9 (Statistical Considerations) was 
updated in line with the changes to 
objectives, estimands, and endpoints.

Updated the planned number of 
participants required for Part 2 of the 
study.

Removed review of temporary delay of 
vaccination criteria at Visit 1 in SoA and 
Section 8.11.1 (Visit 1) and revised text in 
Section 5.5 (Temporary Delay Criteria).

Updated Section 2.3.1.

Addressed discrepancy in 
Section 8.11.1 (Visit 1) describing site 
staff responsibilities for the IRT system 
entries (Impala) compared with text in the 
Impala quick reference guide, IP manual,
and site blinding plan.

Updated Section 10.4.1 (Male Participant 
Reproductive Inclusion Criteria) to correct 
a typographical error.
Original protocol
18 Jan 2021
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs.

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
1. PROTOCOL SUMMARY.....................................................................................................9
1.1. Synopsis ....................................................................................................................9
1.2. Schema ....................................................................................................................13
1.3. Schedule of Activities .............................................................................................14
1.3.1. Schedule of Activities for Those Participants Who Originally 
Received Lyophilized Formulation and Accept the Offer to Receive 
Current Frozen Formulation of BNT162b2.....................................................16
2. INTRODUCTION ...............................................................................................................18
2.1. Study Rationale .......................................................................................................18
2.2. Background .............................................................................................................18
2.2.1. Clinical Overview.......................................................................................19
2.3. Benefit/Risk Assessment.........................................................................................22
2.3.1. Risk Assessment.........................................................................................24
2.3.2. Benefit Assessment.....................................................................................26
2.3.3. Overall Benefit/Risk Conclusion................................................................26
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................26
4. STUDY DESIGN.................................................................................................................27
4.1. Overall Design.........................................................................................................27
4.2. Scientific Rationale for Study Design.....................................................................28
4.3. Justification for Dose ..............................................................................................29
4.4. End of Study Definition ..........................................................................................29
5. STUDY POPULATION......................................................................................................29
5.1. Inclusion Criteria.....................................................................................................29
5.2. Exclusion Criteria....................................................................................................30
5.3. Lifestyle Considerations..........................................................................................31
5.3.1. Contraception..............................................................................................31
5.4. Screen Failures ........................................................................................................31
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Study 
Intervention Administration ......................................................................................32
6. STUDY INTERVENTION..................................................................................................33
6.1. Study Intervention(s) Administered........................................................................33

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
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6.1.1. Administration............................................................................................33
6.2. Preparation/Handling/Storage/Accountability ........................................................34
6.2.1. Preparation and Dispensing........................................................................35
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................35
6.3.1. Allocation to Study Intervention ................................................................35
6.3.2. Blinding of Site Personnel..........................................................................36
6.3.3. Blinding of the Sponsor..............................................................................36
6.3.4. Breaking the Blind......................................................................................37
6.4. Study Intervention Compliance...............................................................................37
6.5. Concomitant Therapy..............................................................................................37
6.5.1. Prohibited During the Study.......................................................................37
6.5.2. Permitted During the Study ........................................................................38
6.6. Dose Modification...................................................................................................38
6.7. Intervention After the End of the Study..................................................................38
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................39
7.1. Discontinuation of Study Intervention ....................................................................39
7.2. Participant Discontinuation/Withdrawal From the Study.......................................39
7.2.1. Withdrawal of Consent...............................................................................40
7.3. Lost to Follow-up....................................................................................................40
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................41
8.1. Efficacy and/or Immunogenicity Assessments .......................................................42
8.1.1. Biological Samples.....................................................................................42
8.2. Safety Assessments .................................................................................................43
8.2.1. Clinical Safety Laboratory Assessments ....................................................43
8.2.2. Electronic Diary..........................................................................................43
8.2.2.1. Grading Scales...........................................................................44
8.2.2.2. Local Reactions.........................................................................44
8.2.2.3. Systemic Events ........................................................................45
8.2.2.4. Fever..........................................................................................46
8.2.2.5. Antipyretic Medication .............................................................46
8.2.3. Pregnancy Testing ......................................................................................46

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
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8.3. Adverse Events and Serious Adverse Events..........................................................47
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......47
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................48
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................48
8.3.2. Method of Detecting AEs and SAEs ..........................................................48
8.3.3. Follow-up of AEs and SAEs.......................................................................48
8.3.4. Regulatory Reporting Requirements for SAEs...........................................49
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................49
8.3.5.1. Exposure During Pregnancy......................................................49
8.3.5.2. Exposure During Breastfeeding ................................................51
8.3.5.3. Occupational Exposure .............................................................51
8.3.6. Cardiovascular and Death Events...............................................................51
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................51
8.3.8. Adverse Events of Special Interest.............................................................52
8.3.8.1. Lack of Efficacy........................................................................52
8.3.9. Medical Device Deficiencies......................................................................52
8.3.10. Medication Errors.....................................................................................52
8.4. Treatment of Overdose............................................................................................53
8.5. Pharmacokinetics ....................................................................................................53
8.6. Pharmacodynamics..................................................................................................53
8.7. Genetics...................................................................................................................53
8.8. Biomarkers ..............................................................................................................54
8.9. Immunogenicity Assessments.................................................................................54
8.10. Health Economics .................................................................................................54
8.11. Study Procedures...................................................................................................54
8.11.1. Visit 1 – Vaccination 1 (Day 1)................................................................54
8.11.2. Visit 2 – Vaccination 2 (19 to 23 Days After Visit 1)..............................56
8.11.3. Visit 3 – 1-Month Follow-up (28 to 35 Days After Visit 2).....................59
8.11.4. Unscheduled Visits for a Grade 3 or Suspected Grade 4 Reaction ..........59
8.12. Study Procedures for Participants Who Accept the Offer to Receive Dose 3 ......60
8.12.1. Visit 101 – Vaccination 3 (At Least 90 Days After Visit 2) ....................60

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Final Protocol Amendment 2, 13 Sep 2021
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8.12.2. Visit 102 – 1-Month Follow-up (28 to 35 Days After Visit 101).............63
8.13. Additional Procedures for Monitoring of Potential Myocarditis or 
Pericarditis.................................................................................................................63
9. STATISTICAL CONSIDERATIONS ................................................................................64
9.1. Estimands and Statistical Hypotheses.....................................................................64
9.1.1. Estimands....................................................................................................64
9.1.2. Statistical Hypothesis..................................................................................64
9.1.3. Multiplicity Considerations ........................................................................65
9.2. Sample Size Determination.....................................................................................65
9.3. Analysis Sets ...........................................................................................................66
9.4. Statistical Analyses .................................................................................................66
9.4.1. General Considerations...............................................................................66
9.4.1.1. Analysis for Binary Data...........................................................67
9.4.1.2. Analysis for Continuous Data ...................................................67
9.4.2. Primary Endpoint(s)....................................................................................68
9.4.3. Secondary Endpoint(s)................................................................................68
9.4.4. Exploratory Endpoint(s) .............................................................................69
9.5. Interim Analyses .....................................................................................................70
9.6. Data Monitoring Committee or Other Independent Oversight Committee.............70
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.........................................................................71
10.1.2. Financial Disclosure .................................................................................72
10.1.3. Informed Consent Process ........................................................................72
10.1.4. Data Protection .........................................................................................73
10.1.5. Dissemination of Clinical Study Data ......................................................73
10.1.6. Data Quality Assurance ............................................................................74
10.1.7. Source Documents....................................................................................76
10.1.8. Study and Site Start and Closure ..............................................................76
10.1.9. Publication Policy.....................................................................................77

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Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
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10.1.10. Sponsor’s Qualified Medical Personnel .................................................77
10.2. Appendix 2: Clinical Laboratory Tests .................................................................78
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................79
10.3.1. Definition of AE .......................................................................................79
10.3.2. Definition of SAE.....................................................................................80
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................82
10.3.4. Reporting of SAEs....................................................................................85
10.4. Appendix 4: Contraceptive Guidance ...................................................................86
10.4.1. Male Participant Reproductive Inclusion Criteria....................................86
10.4.2. Female Participant Reproductive Inclusion Criteria.................................86
10.4.3. Woman of Childbearing Potential ............................................................87
10.4.4. Contraception Methods.............................................................................88
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-up Assessments ........90
10.6. Appendix 6: Abbreviations ...................................................................................92
11. REFERENCES ..................................................................................................................95
LIST OF TABLES
Table 1.
Local Reaction Grading Scale ..................................................................44
Table 2.
Systemic Event Grading Scale..................................................................45
Table 3.
Scale for Fever..........................................................................................46
Table 4.
Power Analysis for Noninferiority Assessment .......................................65

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
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1. PROTOCOL SUMMARY
1.1. Synopsis
Short Title: A Phase 3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of 
Multiple Formulation of BNT162b2 Against COVID-19 in Healthy Adults
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.
Based on Phase 2/3 safety, immunogenicity, and efficacy data, BNT162b2 was shown to be 
effective and has been authorized for temporary or emergency use in multiple countries.
The Pfizer-BioNTech COVID-19 vaccine (also referred to as BNT162b2) is administered 
intramuscularly as a 2-dose series spaced 21 days apart at a dose of 30 μg each. Study 
C4591001 (NCT04368728) is an ongoing Phase 1/2/3 trial in ~44,000 participants designed 
to generate safety, tolerability, immunogenicity, and efficacy data from a novel RNA-based 
vaccine candidate.  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). 
BNT162b2 was selected from the Phase 1 part of this study based on the overall safety, 
tolerability, and immunogenicity. Vaccine efficacy from Phase 2/3 for the primary endpoint 
against confirmed COVID-19 occurring at least 7 days after the second dose was 95% with 
8 COVID-19 cases in the active vaccine group compared to 162 COVID-19 cases in the 
placebo group. Data from approximately 38,000 participants randomized 1:1 with a median 
of 2 months of follow-up after the second dose of vaccine showed a favorable safety profile 
at a dose of 30 μg in participants 16 years of age and older.
To optimize storage and distribution of this vaccine on a wide scale, a lyophilized or alternate
formulation that will be stable at standard refrigerator or freezer temperatures is required.
Therefore, this study will compare the safety and tolerability of lyophilized BNT162b2 
presented in SDVs to those of frozen-liquid BNT162b2 in MDVs and determine whether the 
immune response is noninferior. Separately, the study will also describe the safety and 
immunogenicity of frozen-liquid BNT162b2 with LNP size at the upper end of specification 
and RTU BNT162b2 (the immediate manufacturing precursor to the lyophilate).

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
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The primary immunogenicity analysis demonstrated that the immune response elicited by the 
lyophilized formulation did not meet the noninferiority criteria compared to the frozen-liquid 
formulation of BNT162b2. As a result, for the benefit of participants, all study participants 
who received 2 doses of the lyophilized formulation will be offered an additional vaccine 
dose, using the 30-µg dose of frozen-liquid formulation of BTN162b2.
Objectives, Estimands, and Endpoints
Objectives
Estimands
Endpoints
Primary Immunogenicity
To demonstrate that the 
immune response induced by
lyophilized BNT162b2 in 
SDVs is noninferior to the 
immune response induced by 
frozen-liquid BNT162b2 in 
MDVs in participants without 
evidence of SARS-CoV-2 
infection during the study
In participants complying with the key 
protocol criteria (evaluable 
participants):

GMR of lyophilized formulation 
in SDVs to frozen-liquid 
formulation in MDVs 1 month 
after Dose 2

Full-length S-binding IgG 
levels
Primary Safety
To evaluate the safety of 
BNT162b2 when administered 
on a 2-dose schedule in healthy 
adults 18 through 55 years of 
age
In participants receiving at least 
1 dose of study intervention from each 
vaccine group, the percentage of 
participants reporting:

Local reactions for up to 7 days 
following each dose

Systemic events for up to 7 days 
following each dose

AEs and SAEs from Dose 1 
through 1 month after Dose 2

Local reactions (pain at the 
injection site, redness, and 
swelling)

Systemic events (fever, 
fatigue, headache, chills, 
vomiting, diarrhea, new or 
worsened muscle pain, and 
new or worsened joint pain)

AEs

SAEs
Secondary Immunogenicity
To describe the immune 
responses induced by 
lyophilized BNT162b2 in
SDVs and frozen-liquid 
BNT162b2 in MDVs
In evaluable participants from each 
vaccine group:

GMCs at baseline (before Dose 1) 
and 1 month after Dose 2

GMFR from baseline (before 
Dose 1) to 1 month after Dose 2

Full-length S-binding IgG 
levels
Exploratory
To describe the immune 
responses induced by frozen-
liquid BNT162b2 with LNP 
size at the upper end of 
specification and RTU 
BNT162b2 in participants 
without evidence of 
SARS-CoV-2 infection during 
the study
In evaluable participants:

GMR of frozen-liquid BNT162b2 
with LNP size at the upper end of 
specification to frozen-liquid 
BNT162b2 in MDVs 1 month 
after Dose 2

Full-length S-binding IgG 
levels and/or SARS-CoV-2 
neutralizing titers

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
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Objectives
Estimands
Endpoints
To describe the immune 
responses induced by frozen-
liquid BNT162b2 with LNP 
size at the upper end of 
specification and RTU 
BNT162b2
In evaluable participants from each 
vaccine group:

GMCs and/or GMTs at baseline 
(before Dose 1) and 1 month after 
Dose 2

GMFR from baseline (before 
Dose 1) to 1 month after Dose 2

Full-length S-binding IgG 
levels and/or SARS-CoV-2 
neutralizing titers
To describe the safety profile of 
frozen-liquid BNT162b2 
formulation when given as a 
third dose to participants who 
originally received 2 doses of 
the lyophilized formulation of
BNT162b2
In participants who originally received 
2-dose series of the lyophilized 
formulation of BNT162b2:

Local reactions for up to 7 days 
following third dose

Systemic events for up to 7 days 
following third dose

AEs from Dose 3 to 1 month after 
Dose 3

SAEs from Dose 3 to 1 month 
after Dose 3

Local reactions (pain at the 
injection site, redness, and 
swelling)

Systemic events (fever, 
fatigue, headache, chills, 
vomiting, diarrhea, new or 
worsened muscle pain, and 
new or worsened joint pain)

AEs

SAEs
To describe the immune 
response elicited by 
frozen-liquid BNT162b2
formulation when given as a 
third dose following a primary 
series of lyophilized BNT162b2
In evaluable participants who 
originally received a 2-dose series of 
the lyophilized formulation of 
BNT162b2

GMFR from prior to Dose 3 to 
1 month after Dose 3

GMCs and/or GMTs at baseline, 
at 1 month after Dose 2, prior to
Dose 3, and 1 month after Dose 3

Full-length S-binding IgG 
levels and/or SARS-CoV-2 
neutralizing titers

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Overall Design
This is a Phase 3, randomized, observer-blind study to evaluate the safety, tolerability, and 
immunogenicity of multiple formulations of BNT162b2, an RNA-based COVID-19 vaccine, 
administered on a 2-dose schedule in healthy adults 18 through 55 years of age. In Part 1,
participants will be randomized in a 1:1 ratio to 1 of the 2 groups (lyophilized SDV or 
frozen-liquid MDV control for lyophilized SDV). Separately, in Part 2, participants will be 
randomized in a 1:1 ratio to 1 of the 2 groups (frozen-liquid BNT162b2 with LNP size at the 
upper end of specification or RTU BNT162b2). The duration of the study for each 
participant will be approximately 2 months.  The study will be conducted in the US with 
potential to expand to other countries.
Updates as part of protocol amendment 2:
All participants who originally received 2 doses of the lyophilized formulation of BNT162b2
will be offered the opportunity to receive a third dose with the current frozen-liquid 
formulation of BNT162b2. Those participants who accept the offer of receiving a third dose 
will have 2 additional visits. The study duration will be extended for 1 additional month for 
those participants who accept the offer of receiving a third dose.
Number of Participants
Approximately 550 participants will be randomly assigned in a 1:1 ratio to either lyophilized 
SDV or frozen-liquid MDV control for lyophilized SDV; separately, approximately 
60 participants will be randomly assigned in a 1:1 ratio to either frozen-liquid BNT162b2
with LNP size at the upper end of specification or RTU BNT162b2, for a total of 
approximately 610 randomized participants. It is expected that approximately 488 evaluable 
participants will complete the study, based on a 20% nonevaluable rate.
Data Monitoring Committee or Other Independent Oversight Committee: Yes
This study will use a DMC.  The DMC is independent of the study team and includes 
external members.  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.  This may include, but is not limited to:

Contemporaneous review of related AEs up to 1 month after completion of the 
vaccination schedule,

Contemporaneous review of all SAEs up to 1 month after completion of the 
vaccination schedule.
The recommendations made by the DMC to alter the conduct of the study will be forwarded 
to the appropriate Pfizer personnel for final decision.  Pfizer will forward such decisions, 
which may include summaries of aggregate analyses of safety data, to regulatory authorities, 
as appropriate.

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
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Final Protocol Amendment 2, 13 Sep 2021
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Statistical Methods
The primary immunogenicity objective will be evaluated by a formal hypothesis test for 
noninferiority of the full-length S-binding IgG levels induced by lyophilized SDV compared 
to the corresponding frozen-liquid MDV BNT162b2 control.  GMRs will be provided along 
with associated 2-sided 95% CIs. Noninferiority will be declared if the lower bound of the 
2-sided 95% CI for the GMR of lyophilized BNT162b2 relative to frozen-liquid MDV 
BNT162b2 is greater than 0.67 (using a 1.5-fold noninferiority criterion).
With 220 evaluable participants in each of the 2 vaccine groups in Part 1, the study has a 
power of 90.1% for declaring noninferiority of lyophilized BNT162b2 to frozen-liquid MDV 
BNT162b2. Assuming a nonevaluable rate of 20%, the study will randomize approximately 
275 participants to each group in Part 1 of the study to achieve the required number of 
evaluable participants.
The secondary immunogenicity objective will be evaluated descriptively by GMCs, GMFRs, 
and the associated 95% CIs for the full-length S-binding IgG levels for each vaccine group.
The primary safety objective will be evaluated by descriptive statistics including counts and 
percentages of participants and the associated Clopper-Pearson 95% CIs for local reactions, 
systemic events, and AEs/SAEs for each vaccine group.
1.2. Schema
Note: As part of protocol amendment 2, all participants who originally received 2 doses of
the lyophilized formulation of BNT162b2 will be offered the opportunity to receive a third 
dose of the frozen-liquid formulation of BNT162b2.

PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
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Final Protocol Amendment 2, 13 Sep 2021
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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
1-Month Follow-up Visit
Visit Window
Day 1a
19 to 23 Days After Visit 1
28 to 35 Days After Visit 2
Obtain informed consent
X
Assign participant number
X
Obtain demography and medical history data
X
Perform clinical assessmentb
X
Measure height and weight
X
Measure temperature (body)
X
X
Perform urine pregnancy test (if appropriate)
X
X
Confirm use of contraceptives (if appropriate)
X
X
X
Collect nonstudy vaccine information
X
X
X
Collect prohibited medication use
X
X
Confirm eligibility
X
X
Review temporary delay criteria
X
Collect blood sample for immunogenicity assessment & for 
serological testing for prior COVID-19 infectionc
~20 mL
~20 mL
Obtain nasal (midturbinate) swab for determination of current 
SARS-CoV-2 statusc
X
X
Obtain randomization number and study intervention 
allocation
X
Administer study intervention
X
X

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Visit Number
1
2
3
Visit Description
Vaccination 1
Vaccination 2
1-Month Follow-up Visit
Visit Window
Day 1a
19 to 23 Days After Visit 1
28 to 35 Days After Visit 2
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
Collect AEs and SAEs 
X
X
Xd
Collect e-diary or assist the participant to delete the 
application
X
Abbreviations: = continuous/ongoing event; e-diary = electronic diary.
a.
The visit may be conducted across 2 consecutive days; if so, all steps from assessing the inclusion and exclusion criteria onward must be conducted on the 
same day.
b.
Including, if indicated, a physical examination.
c.
Administration of study intervention is not dependent on test results.
d.
Any AEs occurring up to 48 hours after blood draw and nasal swab collection must be recorded.

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1.3.1. Schedule of Activities for Those Participants Who Originally Received Lyophilized Formulation and Accept the Offer to 
Receive Current Frozen Formulation of BNT162b2
Visit Number
101
102
Visit Description
Vaccination 3
1-Month Follow-up Visit
Visit Window
At Least 90 Days After Vaccination 2
28 to 35 Days After Visit 101
Obtain informed consent
X
Confirm participant originally received BOTH 
doses of lyophilized formulation of BNT162b2
X
Measure prevaccination temperature (body)
X
Perform urine pregnancy test (if appropriate)
X
Confirm use of contraceptives (if appropriate)
X
X
Collect nonstudy vaccine information
X
X
Collect prohibited medication use
X
X
Review and consider eligibilitya
X
Review temporary delay criteria
X
Collect blood sample for immunogenicity 
assessment
~20 mL
~20 mL
Obtain nasal (midturbinate) swab for determination 
of current SARS-CoV-2 statusb
X
X
Obtain study intervention allocation using the IRT 
system
X
Administer study intervention
X
Assess acute reactions for at least 30 minutes after 
study intervention administration
X
Provide thermometer and measuring device
X
Remind participant of e-diary technologies
X
Review reactogenicity e-diary data (daily review is 
optimal during the active diary period)
X

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Visit Number
101
102
Visit Description
Vaccination 3
1-Month Follow-up Visit
Visit Window
At Least 90 Days After Vaccination 2
28 to 35 Days After Visit 101
Review ongoing reactogenicity e-diary symptoms 
and obtain stop dates 
X
X
Collect AEs and SAEs as appropriatec
X
Xc
Collect e-diary or assist the participant to delete 
application
X
Abbreviations: e-diary = electronic diary; IRT = interactive response technology.
a.
Confirm that the participant meets all of the inclusion criteria and does not meet exclusion criteria 1, 3, 5, 6, 7, 10, 11, 12, 13, and 14.
b.
Administration of study intervention is not dependent on test results
c.
Any AEs occurring up to 48 hours after blood draw and nasal swab collection must be recorded.

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2. INTRODUCTION
BNT162b2 is an RNA-based COVID-19 vaccine that is currently in use via either emergency 
(temporary) use or conditional marketing authorizations in approximately 70 countries for 
the prevention of COVID-19 in individuals ≥16 years of age. BNT162b2 received first 
temporary authorization for emergency supply under regulation 174 in the UK on 
01 December 2020 and is currently authorized for emergency use in 30 countries. 
BNT162b2 received first regulatory conditional marketing authorization approval in 
Switzerland on 19 December 2020 and is currently conditionally approved in 40 countries.
2.1. Study Rationale
The purpose of this study is to demonstrate that the immune response induced by the 
refrigerator-stable lyophilized formulation of BNT162b2 is noninferior to the frozen-liquid 
formulation of BNT162b2 in MDVs, and to describe the safety and tolerability of these 
different vaccine formulations in healthy adults, thereby supporting refrigerated storage and
distribution at commercial scale. The study will also describe the safety and immunogenicity 
of frozen-liquid BNT162b2 with LNP size at the upper end of specification and RTU 
BNT162b2.
Current clinical and EUA specifications for LNP size for the frozen-liquid formulation are 40
to 180 nm and 40 to 120 nm, respectively. Clinical experience, however, is limited to LNP 
size in the range 59 to 74 nm, based on lots used in the clinical studies already conducted. 
Hence, an exploratory study arm is being included to better understand the impact of LNP 
size, using a lot with LNP size close to the upper specification boundary (without any 
significant impact on other quality attributes).  The immediate manufacturing precursor of 
the lyophilized formulation is the RTU. An exploratory study arm is included to describe the 
safety and immunogenicity of the RTU (ie, precursor prior to the lyophilization step).
The primary immunogenicity analysis demonstrated that the immune response elicited by the 
lyophilized formulation did not meet the noninferiority criteria compared to the frozen-liquid 
formulation of BNT162b2. As a result, for the benefit of the participants, all study 
participants who received 2 doses of the lyophilized formulation will be offered an additional
vaccine dose, using the 30-µg dose of the frozen-liquid formulation of BNT162b2.
2.2. Background
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China.  
In January 2020, it became clear that a novel coronavirus (2019-nCoV) was the underlying 
cause.  Later in January, the genetic sequence of the 2019-nCoV became available to the 
WHO and the public (MN908947.3), and the virus was categorized in the Betacoronavirus
subfamily.  By sequence analysis, the phylogenetic tree revealed a closer relationship to 
SARS virus isolates than to another coronavirus infecting humans, the MERS virus.1,2
The outbreak was declared a Public Health Emergency of International Concern on 
30 January 2020.3  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).3  SARS-CoV-2 

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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.4  On 08 January 2021, The 
Center for Systems Science and Engineering at Johns Hopkins University reported more than 
88 million cases globally, with over 1.9 million deaths from 191 countries.  The 
United States has reported more than 21.6 million cases and over 366,000 deaths.5
Since fall of 2020, the incidence of COVID-19 illnesses is increasing dramatically in many 
northern hemisphere countries, including the United States, France, Germany, Italy, and the 
United Kingdom, raising the specter that as temperatures have fallen and the “respiratory 
virus season” has started, cases may dramatically increase, potentially overwhelming 
healthcare infrastructures. This possibility highlights the importance of developing a 
COVID-19 vaccine as quickly as possible while ensuring that all safety measures are met.
A prophylactic, RNA-based SARS-CoV-2 vaccine provides one of the most flexible and 
fastest approaches available to immunize against the emerging virus.6,7 In an attempt to 
prevent the spread of disease and to control the pandemic, numerous COVID-19 vaccine 
candidates are in development.
The development of an RNA-based vaccine encoding a viral antigen, which is then expressed 
by the vaccine recipient as a protein capable of eliciting protective immune responses, 
provides significant advantages over more traditional vaccine approaches.  Unlike live 
attenuated vaccines, RNA vaccines do not carry the risks associated with infection and may 
be given to people who cannot be administered live virus (eg, pregnant women and 
immunocompromised persons).  RNA-based vaccines are manufactured via a cell-free 
in vitro transcription process, which allows an easy and rapid production and the prospect of 
producing high numbers of vaccination doses within a shorter time period than achieved with 
traditional vaccine approaches.  This capability is pivotal to enable the most effective 
response in outbreak scenarios.6,7
BNT162b2 is a SARS-CoV-2–RNA-LNP vaccine based on a platform of modRNA with 
blunted innate immune sensor–activating capacity and augmented expression encoding P2 S.
2.2.1. Clinical Overview
Study C4591001 (NCT04368728) is an ongoing Phase 1/2/3 trial in ~44,000 participants 
designed to generate safety, tolerability, immunogenicity, and efficacy data from a novel 
RNA-based vaccine candidate.8  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). BNT162b2 was selected from the Phase 1 part of this 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, efficacy in preventing 

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confirmed COVID-19 occurring at least 7 days after the second dose of vaccine was 95.0%, 
with 8 COVID-19 cases in the active vaccine group and 162 COVID-19 cases in the placebo 
group. Subgroup analyses of the primary efficacy endpoint showed similar efficacy point 
estimates across age groups, sexes, racial and ethnic groups, and participants with medical 
comorbidities associated with high risk of severe COVID-19. Secondary efficacy analyses 
suggested benefit of the vaccine in preventing severe COVID-19, in preventing COVID-19 
following the first dose, and in preventing COVID-19 in individuals with prior SARS-CoV-2 
infection, although available data for these outcomes did not allow for firm conclusions.9
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 suggest 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.9
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. Among 
nonserious unsolicited AEs, there was a numerical imbalance of 4 cases of Bell’s palsy in the 
active vaccine group compared with no cases in the placebo group, though the 4 cases in the 
active vaccine group do not represent a frequency above that expected in the general 
population. 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.9
In the C4591001 study, the Phase 1 population included healthy participants 18 through 55 
and 65 through 85 years of age.  Enrollment in Phase 1 is complete and, although follow-up 
continues, the available safety data from Phase 1 participants show that BNT162b2 
reactogenicity, AEs, and laboratory results were consistent with those commonly associated 
with vaccination.  The observed reactogenicity was generally mild or moderate (primarily 
pain at the injection site) and short-lived.  The local reactions tended to be more frequent 
after the second dose.  There was no redness or swelling reported by participants in the 
65- through 85-year age group who received BNT162b2.10
Regarding systemic events, 17% of the 18- through 55-year age group and 8% of those in the 
65- through 85-year age group reported fever (≥38.0°C to 38.9°C) after the second dose of 

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30 µg of BNT162b2.  Severe systemic events (fatigue, headache, chills, muscle pain, and 
joint pain) were reported in small numbers of younger recipients of this vaccine candidate, 
but no severe systemic events were reported in older recipients, and there were no Grade 4 
systemic events reported.10
No unexpected AEs or SAEs were reported.  Through 1 month after receipt of the second 
vaccination, AEs that were considered by investigators to be related to the study intervention 
were reported in 25% of participants 18 through 55 years of age who received 30 µg of 
BNT162b2; no AEs were reported by the older population who received the same dose.10
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 Th 1–skewed CD4+ response and a strong antigen-specific 
CD8+ response.
Based on the safety, tolerability, and immunogenicity data generated from Phase 1, the 
vaccine candidate selected for the Phase 2/3 part of the study was BNT162b2 at a dose 
of 30 µg.  This phase of the study is currently ongoing and is evaluating the efficacy of the 
study intervention.
The Phase 2/3 portion of C4591001 was initiated in 18- through 85-year-old adults but was 
amended in September 2020 to include participants ≥16 years of age.  It is intended that a 
minimum of 40% of participants will be in the >55-year stratum. A further protocol 
amendment in October 2020 added a stratum of 2000 participants (1000 active vaccine) 
12 through 15 years of age.  The first 360 participants in the Phase 2/3 part of the study will 
be considered the Phase 2 segment but will also contribute to the efficacy endpoint.
There are 2 primary efficacy endpoints in the Phase 2/3 part of the study.  The first is to 
evaluate the efficacy of prophylactic BNT162b2 against confirmed COVID-19 in participants 
without evidence of infection before vaccination and the second is to evaluate the efficacy of 
prophylactic BNT162b2 against confirmed COVID-19 in participants regardless of evidence 
of infection before vaccination.  Cases of COVID-19 are defined by the presence of specified 
symptoms plus an NAAT for SARS-CoV-2 at least 7 days following the second dose of 
vaccine.  Effectiveness in 12- to 15-year-old participants will be inferred by immune 
noninferiority to that in 16- to 25-year-old participants based on SARS-CoV-2–neutralizing 
GMTs.
The primary safety objective includes definition of the safety profile of prophylactic 
BNT162b2 in the first 360 participants in the Phase 2 population, in all participants 
randomized in Phase 2/3, and in 12- to 15-year-old participants.  Reactogenicity will be 
assessed by e-diary in all participants in Phase 1, in at least 6000 participants in Phase 2/3, 
and in all participants 12 through 15 years of age.
The scale of the BNT162b2 manufacturing has been increased to support future supply.  
Therefore, in the C4591001 Phase 2/3 phase of the study, BNT162b2 generated using the 

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manufacturing process supporting an increased supply (“Process 2”) was administered to 
approximately 250 participants 16 through 55 years of age, per lot.
The currently available safety and immunogenicity data are presented in the BNT162 IB.11
2.3. Benefit/Risk Assessment
There is an ongoing global pandemic of COVID-19 and, based on the data available from the 
C4591001 study, multiple temporary or emergency use authorizations and conditional 
marketing authorizations have been granted for BNT162b2. The available safety and 
immunogenicity data from the ongoing Pfizer/BioNTech clinical trial 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%).9 Adverse reactions characterized as reactogenicity were generally mild to 
moderate. The number of participants reporting hypersensitivity-related AEs was 
numerically higher in the active 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 older adults (>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 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.9
No specific safety concerns were identified in subgroup analyses by age, race, ethnicity, 
medical comorbidities, or prior SARS-CoV-2 infection. Although participants 16 through
17 years of age were enrolled in the Phase 3 trial, safety data for this age group are limited. 
However, available data are consistent with the safety profile in the adult population, and it is 
biologically reasonable to extrapolate the greater safety experience in adults, in particular 
younger adults, to the oldest pediatric age group of 16 through 17 years.  The potential 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.9 Continued clinical investigation is justified 
given:

the urgent need to optimize storage and distribution of a COVID-19 vaccine on a 
wide scale using a lyophilized formulation that will be stable at standard refrigerator 
temperatures,

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
the threat posed by the increasing number of globally distributed outbreaks of 
SARS-CoV-2 infection,

the potential of the BioNTech platform of RNA-based vaccines to rapidly deliver 
high numbers of vaccine doses in a single production campaign.
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.

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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention: BNT162b2 RNA-Based COVID-19 Vaccine
Local and systemic reactions to the vaccine 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.

The study employs the use of a reactogenicity 
e-diary to monitor local reactions and systemic 
events in real time.

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: 
Anaphylaxis, other hypersensitivity reactions 
(eg, rash, pruritus, urticaria, angioedema), pain in 
extremity (injected arm).
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.
Postauthorization safety data surveillance has 
confirmed the safety profile observed in C4591001 
and has resulted in identification of some additional 
adverse reactions (risks) as noted in this table.

Collection of AE and SAE reports from signing 
of the ICD through 1 month after the second 
dose of vaccine.

DMC throughout the study to review all safety 
data.

All participants will be observed for at least 
30 minutes after vaccination.
Potential for COVID-19 enhancement.
Disease enhancement has been seen following 
vaccination with RSV, feline coronavirus, and 
Dengue virus vaccines. No evidence of disease 
enhancement has been seen in large-scale clinical 
study of BNT162b2 in humans or in 
postauthorization surveillance.

Eligibility criteria will exclude any participants 
who have had a previous clinical 
(signs/symptoms only) or microbiological 
(signs/symptoms and positive SARS-CoV-2 
NAAT result) diagnosis of COVID-19. This 
will minimize the low risk of potential disease 
enhancement and ensure that the immune 
response evaluated in the study is not impacted 
by serological changes due to previous 
COVID-19 disease.

Monitoring for cases of COVID-19 developing 
during the study, which will be reported as 
AESIs.

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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
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.

Pfizer will work with sites to ensure an 
appropriate COVID-19 prevention strategy.

The study will include monitoring for cases of 
COVID-19 developing during the study, which 
will be reported as AESIs.
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.
Very rare cases of anaphylaxis, myocarditis, and 
pericarditis have been reported after EUA 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, these 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 observation 
period of 30-minute after vaccination.
Instructions for handling suspected cases of 
myocarditis and pericarditis are found in 
Section 8.13.

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2.3.2. Benefit Assessment
Benefits to individual participants may include:

Receipt of an efficacious or potentially efficacious COVID-19 vaccine during a 
global pandemic

Access to COVID-19 diagnostic testing

Contributing to research to help others in a time of global pandemic
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risks to participants participating in this 
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 Immunogenicity
To demonstrate that the immune 
response induced by lyophilized 
BNT162b2 in SDVs is 
noninferior to the immune 
response induced by frozen-
liquid BNT162b2 in MDVs in 
participants without evidence of 
SARS-CoV-2 infection during 
the study
In participants complying with the 
key protocol criteria (evaluable 
participants):

GMR of lyophilized 
formulation in SDVs relative 
to frozen-liquid formulation in 
MDVs 1 month after Dose 2

Full-length S-binding IgG 
levels
Primary Safety
To evaluate the safety of 
BNT162b2 when administered 
on a 2-dose schedule in healthy 
adults 18 through 55 years of 
age
In participants receiving at least 
1 dose of study intervention from 
each vaccine group, the percentage 
of participants reporting:

Local reactions for up to 
7 days following each dose

Systemic events for up to 
7 days following each dose

AEs and SAEs from Dose 1 
through 1 month after Dose 2

Local reactions (pain at the 
injection site, redness, and 
swelling)

Systemic events (fever, 
fatigue, headache, chills, 
vomiting, diarrhea, new or 
worsened muscle pain, and 
new or worsened joint pain)

AEs

SAEs
Secondary Immunogenicity
To describe the immune 
responses induced by lyophilized 
BNT162b2 in SDVs and 
frozen-liquid BNT162b2 in 
MDVs
In evaluable participants from each 
vaccine group:

GMCs at baseline (before 
Dose 1) and 1 month after 
Dose 2

GMFR from baseline (before 
Dose 1) to 1 month after 
Dose 2

Full-length S-binding IgG 
levels

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Objectives
Estimands
Endpoints
Exploratory
To describe the immune 
responses induced by frozen-
liquid BNT162b2 with LNP size 
at the upper end of specification 
and RTU BNT162b2 in 
participants without evidence of 
SARS-CoV-2 infection during 
the study
In evaluable participants:

GMR of frozen-liquid 
BNT162b2 with LNP size at 
the upper end of specification 
relative to frozen-liquid 
BNT162b2 in MDVs 1 month 
after Dose 2

Full-length S-binding IgG 
levels and/or SARS-CoV-2 
neutralizing titers 
To describe the immune 
responses induced by frozen-
liquid BNT162b2 with LNP size 
at the upper end of specification 
and RTU BNT162b2
In evaluable participants from each 
vaccine group:

GMCs and/or GMTs at 
baseline (before Dose 1) and 
1 month after Dose 2

GMFR from baseline (before 
Dose 1) to 1 month after 
Dose 2

Full-length S-binding IgG 
levels and/or SARS-CoV-2 
neutralizing titers
To describe the safety profile of 
frozen-liquid BNT162b2 
formulation when given as a 
third dose to participants who 
originally received 2 doses of the 
lyophilized formulation of
BNT162b2
In participants who originally 
received 2 dose series of the 
lyophilized formulation of 
BNT162b2:

Local reactions for up to 7 days 
following third dose

Systemic events for up to 
7 days following third dose

AEs from Dose 3 to 1 month 
after Dose 3

SAEs from Dose 3 to 1 month 
after Dose 3

Local reactions (pain at the 
injection site, redness, and 
swelling)

Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened 
muscle pain, and new or 
worsened joint pain)

AEs

SAEs
To describe the immune 
response elicited by frozen-
liquid BNT162b2 formulation 
when given as third
dose following a primary series 
of lyophilized BNT162b2
In evaluable participants who 
originally received 2 dose series of 
the lyophilized formulation of 
BNT162b2

GMFR from prior to Dose 3 to 
1 month after Dose 3

GMCs and/or GMTs at 
baseline, at 1 month after Dose 
2, prior to Dose 3 and 1 month 
after Dose 3 

Full-length S-binding IgG 
levels and/or SARS-CoV-2 
neutralizing titers
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 3, randomized, observer-blind study to evaluate the safety, tolerability, and 
immunogenicity of multiple formulations of BNT162b2, an RNA-based COVID-19 vaccine, 
administered on a 2-dose schedule in healthy adults 18 through 55 years of age. The study 
will be conducted in the US with potential to expand to other countries.

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In Part 1, participants will receive either lyophilized BNT162b2 in SDVs or frozen-liquid 
BNT162b2 in MDVs.  In Part 2, participants will receive either frozen-liquid BNT162b2 
with LNP size at the upper end of specification or RTU BNT162b2. In Part 1, participants 
will be randomized in a 1:1 ratio to 1 of the 2 groups (lyophilized SDV or frozen-liquid 
MDV control for lyophilized SDV). Separately, in Part 2, participants will be randomized in 
a 1:1 ratio to 1 of the 2 groups (frozen-liquid BNT162b2 with LNP size at the upper end of 
specification or RTU BNT162b2). The duration of the study for each participant will be 
approximately 2 months. Approximately 550 participants will be randomly assigned to 
either lyophilized SDV or frozen-liquid MDV control for lyophilized SDV; separately, 
approximately 60 participants will be randomly assigned to receive either frozen-liquid 
BNT162b2 with LNP size at the upper end of specification or RTU BNT162b2, for a total of 
approximately 610 randomized participants. It is expected that approximately 488 evaluable 
participants will complete the study, based on a 20% nonevaluable rate.
Updates as part of protocol amendment 2: 
All participants who originally received 2 doses of the lyophilized formulation of BNT162b2 
will be offered the opportunity to receive a third dose with the current frozen-liquid 
formulation of BNT162b2. Those participants who accept the offer of receiving third dose 
will have 2 additional visits as described in Section 1.3.1. The study duration will be 
extended for 1 additional month for those participants who accept the offer of receiving a 
third dose.
4.2. Scientific Rationale for Study Design
This study contains assessments that could be considered standard for a vaccine 
noninferiority study.  Blood samples taken for immunogenicity will establish the level of 
immune response elicited by each formulation to provide the necessary data to meet the 
primary endpoint of the study.  Immunogenicity will be assessed by the full-length S-binding 
IgG assay.  To establish if a participant has asymptomatic SARS-CoV-2 infection, nasal 
swabs for SARS-CoV-2 nucleic acid amplification testing (ie, NAAT) and blood samples to 
measure N-binding antibody levels will be taken.  A positive result on either test will result 
in the immunogenicity data from that participant being excluded from the evaluable portion 
of the study population.  All reactogenicity and safety assessments are standard for a study of 
this nature.
This study will not include a placebo, as the aim and design of this study are not to 
demonstrate efficacy.
Human reproductive safety data are not available for BNT162b2, but there is no suspicion of 
human teratogenicity based on the intended mechanism of action of the compound.  
Therefore, the use of a highly effective method of contraception is required (see Appendix 4).

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4.3. Justification for Dose
Based on data from the Phase 1 component of clinical trial C4591001 and available 
nonclinical data, the modRNA BNT162b2 vaccine candidate was selected at a dose of 30 µg 
for Phase 2/3 evaluation of safety, immunogenicity, and efficacy. This is the dose that has 
shown to be effective and has been authorized for temporary or emergency use.
Update based on protocol amendment 2:
The primary immunogenicity analysis demonstrated that the immune response elicited by the 
lyophilized formulation did not meet the noninferiority criteria compared to the frozen-liquid 
formulation. Therefore, all study participants who received 2 doses of the lyophilized 
formulation will be offered an additional 30-ug dose of the frozen-liquid formulation.
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last visit.
The end of the study is defined as the date of the last visit of the last participant in the study.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  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. Male or female participants between the ages of 18 and 55 years, inclusive, at Visit 1 
(Day 1).

Refer to Section 10.4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Participants who 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. Healthy participants who are determined by medical history, physical examination 
(if required), and clinical judgment of the investigator to be eligible for inclusion in the 
study.
Note: Healthy participants with preexisting stable disease, defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease during 
the 6 weeks before enrollment, can be included.
Informed Consent:
4. 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. For Dose 3: Participants who received BOTH doses of the lyophilized formulation of 
BNT162b2 as part of the initial study.
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. Known infection with HIV, HCV, or HBV.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study intervention(s).
4. Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT 
result was not available) or microbiological (based on COVID-19 symptoms/signs and a 
positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
5. Immunocompromised individuals with known or suspected immunodeficiency, as 
determined by history and/or laboratory/physical examination.
6. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
7. Women who are pregnant or breastfeeding.
Prior/Concomitant Therapy:
8. Previous vaccination with any coronavirus vaccine.

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9. Receipt of medications intended to prevent COVID-19.
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 
cancer or an autoimmune disease, 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.
Prior/Concurrent Clinical Study Experience:
12. Participation in other studies involving study intervention within 28 days prior to study 
entry and/or during study participation.
13. Previous participation in other studies involving study intervention containing LNPs.
Other Exclusions:
14. 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 10.4.4) 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 highly effective contraception consistently and correctly and document the 
conversation and the participant’s affirmation in the participant’s chart (participants need to 
affirm their consistent and correct use of at least 1 of the selected methods of contraception).  
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued or if pregnancy is known or suspected in the 
participant or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention.  A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure participants to 
meet the CONSORT publishing requirements and to respond to queries from regulatory 

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authorities.  Minimal information includes demography, screen failure details, eligibility 
criteria, and any SAEs.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened under a different participant number.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Study Intervention 
Administration
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 (body temperature ≥100.4°F [≥38.0°C]) or other acute illness 
within 48 hours before study intervention administration.  This includes current 
symptoms that could represent a potential COVID-19 illness:

New or increased cough;

New or increased shortness of breath;

Chills;

New or increased muscle pain;

New loss of taste/smell;

Sore throat;

Diarrhea;

Vomiting.
2. Receipt of any seasonal or pandemic influenza vaccine within 14 days, or any other 
nonstudy vaccine within 28 days, before study intervention administration.
3. Anticipated receipt of any seasonal or pandemic influenza vaccine within 14 days, or 
any other 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.

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6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to BNT162b2, an RNA-based 
vaccine for immunization against COVID-19.  One of 3 versions of BNT162b2 (lyophilized,
frozen-liquid, or RTU) will be administered to each participant.  The study will evaluate a 
2-dose (separated by 21 days) schedule in healthy adults 18 through 55 years of age.
6.1. Study Intervention(s) Administered
Intervention Name
BNT162b2 
(BNT162 RNA-LNP 
vaccine utilizing 
modRNA)
BNT162b2 
(BNT162 RNA-LNP 
vaccine utilizing 
modRNA)
BNT162b2 
(BNT162 RNA-LNP 
vaccine utilizing 
modRNA)
Arm Name
(group of participants 
receiving a specific 
vaccine or no vaccine)
Frozen-liquid MDV
Lyophilized SDV
RTU SDV
Type
Vaccine
Vaccine
Vaccine
Dose Formulation
modRNA
modRNA
modRNA
Dosage Level
30 µg
30 µg
30 µg
Route of 
Administration
Intramuscular injection
Intramuscular injection
Intramuscular injection
Use
Experimental
Experimental
Experimental
IMP or NIMP
IMP
IMP
IMP
Sourcing
Provided centrally by the 
sponsor
Provided centrally by the 
sponsor
Provided centrally by the 
sponsor
Packaging and 
Labeling
Study intervention will be 
provided in a glass vial.  
Each vial will be labeled 
as required per country 
requirement.
Study intervention will be 
provided in a glass vial.  
Each vial will be labeled 
as required per country 
requirement.
Study intervention will be 
provided in a glass vial.  
Each vial will be labeled 
as required per country 
requirement.
6.1.1. Administration
Participants will receive 1 dose of study intervention as randomized at each vaccination visit 
(Visits 1 and 2) separated by 21 days in accordance with the study’s SOA. Full details are 
described in the IP manual.
Participants who originally received 2 doses of the lyophilized formulation of BNT162b2 
will be offered the opportunity to receive an additional dose of the frozen-liquid formulation 
of BNT162b2 at least 90 days after Dose 2.
Study intervention should be administered intramuscularly into the deltoid muscle, preferably 
of the nondominant arm, by an unblinded administrator.

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Standard vaccination practices must be observed and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of study interventions should be performed by an appropriately qualified, 
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/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.  The 
temperature of all locations where study intervention is stored at a clinical site must 
be monitored continuously.  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.
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.

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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 preparation 
and dispensing.
Study intervention will be prepared by qualified unblinded site personnel according to the IP 
manual.  The study intervention will be administered in such a way as to ensure the 
participants remain blinded.
Requirements for site personnel to be blinded for the Dose 3 preparation are not applicable.
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 vaccine assignment and randomization number.  The IRT system will 
provide a confirmation report containing the participant number, randomization number, and 
study intervention allocation assigned.  The confirmation report must be stored in the site’s 
files.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.

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6.3.2. 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.
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.  Once the study intervention has 
been prepared, there is no difference in the physical appearance of the BNT162b2 
formulations. 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.
Update based on protocol amendment 2: 
After the complete data through 1 month after Dose 2 for Part 1 participants were available, 
the database for Part 1 was released and unblinded for the study team to perform the 
statistical analyses specified for Part 1. Additionally, site staff and study participants were 
also unblinded to participants’ vaccine allocation.
6.3.3. Blinding of the Sponsor
The majority of sponsor staff will be blinded to study intervention allocation.  All laboratory 
testing personnel performing serology assays will remain blinded to study intervention 
assigned/received throughout the study.  The following sponsor 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.

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
After the complete data through 1 month after Dose 2 for Part 1 participants were
available, the database for Part 1 was released and unblinded for the study team to 
perform the statistical analyses specified for Part 1.
6.3.4. Breaking the Blind
All study participants will receive BNT162b2; blinding refers only to which vaccine 
formulation the participant will receive.  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 in the clinic will be recorded in the source documents and recorded in the CRF.  
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention.
6.5. Concomitant Therapy
The following concomitant medications and vaccinations will be recorded in the CRF:

All vaccinations received from 28 days prior to study enrollment until the 1-month 
follow-up visit (Visit 3).

Additionally, for all participants receiving Dose 3, all vaccinations received from 
28 days prior to Visit 101 (Dose 3) until the 1-month follow-up visit (Visit 102).

Prohibited medications listed in Section 6.5.1 will be recorded, to include start and 
stop dates, name of the medication, dose, unit, route, and frequency.
6.5.1. 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.

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
Unless considered medically necessary, no vaccines other than study intervention 
should be administered within 28 days before and 28 days after each study 
vaccination.  One exception to this is that seasonal and pandemic influenza vaccine 
can be given at least 14 days after, or at least 14 days prior to, the administration of 
study intervention.

Receipt of chronic systemic treatment with known immunosuppressant medications, 
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 Visit 3 or Visit 102 
for those participants receiving Dose 3.

Receipt of blood/plasma products or immunoglobulins within 60 days before 
enrollment through conclusion of the study.

Receipt of any other (nonstudy) coronavirus vaccine at any time prior to or during 
study participation is prohibited.

Receipt of prophylactic medications intended to prevent symptoms associated with
COVID-19.  However, if a participant is taking a medication for another condition, 
even if it may have such properties, it should not be withheld prior to study 
vaccination.

Prophylactic antipyretics and other pain medication to prevent symptoms associated 
with study intervention administration are not permitted.  However, if a participant is 
taking a medication for another condition, even if it may have antipyretic or 
pain-relieving properties, it should not be withheld prior to study vaccination.
6.5.2. 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.
Medication other than that described as prohibited in Section 6.5.1 required for treatment of 
preexisting stable conditions is permitted.
Inhaled, topical, or localized injections of corticosteroids (eg, intra-articular or intrabursal 
administration) are permitted.
6.6. Dose Modification
Not applicable for this study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.

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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 (definitive discontinuation).  Reasons for definitive discontinuation of study 
intervention include the following: AEs; participant request; investigator request; pregnancy; 
protocol deviation (including no longer meeting all the inclusion criteria, or meeting 1 or 
more exclusion criteria*).  In general, unless the investigator considers it unsafe to administer 
the second dose, or the participant does not wish to receive it, it is preferred that the second 
dose be administered.
*A positive SARS-CoV-2 NAAT result without symptoms or a COVID-19 diagnosis 
(signs/symptoms only or signs/symptoms and a positive SARS-CoV-2 NAAT result) should 
not result in discontinuation of study intervention.  If study intervention (Dose 2) has been 
delayed per Section 5.5, because of febrile or other acute illness (Item 1 in the list in 
Section 5.5), and the investigator later diagnoses the signs and symptoms as COVID-19 (with 
or without a positive SARS-CoV-2 NAAT result), the participant should not be discontinued 
from any further doses of study intervention.
Note that discontinuation of study intervention does not represent withdrawal from the study.  
Per the study estimands, if study intervention is definitively 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 discontinuation of study intervention and follow-up for any further
evaluations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, postvaccination study follow-up, 
and/or future collection of additional information.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
discontinuation from the study include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;

AEs;

Participant request; 

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
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.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of study intervention or also from study procedures 
and/or postvaccination study follow-up, and entered on the appropriate CRF page.  In the 
event that vital status (whether the participant is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed 
in accordance with local law.
7.3. Lost to Follow-up
A participant will be considered lost to follow-up if 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 and counsel the participant on the importance of maintaining the 

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assigned visit schedule and ascertain whether or not 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 full date of birth will be collected to critically evaluate the immune response and safety 
profile by age.
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.

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The total blood sampling volume for individual participants in this study is approximately 
40 mL.  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 60 consecutive days.
Per protocol amendment 2, those participants who accept the offer to receive Dose 3 will 
have an additional approximately 20-mL blood sample collected for immunogenicity 
assessments at each visit.
8.1. Efficacy and/or Immunogenicity Assessments
Serum samples will be obtained for immunogenicity testing at the visits specified in the SoA.  
The test to be performed will be the SARS-CoV-2 full-length S-binding IgG-level assay.  
Note that all immunogenicity analyses will be based upon samples analyzed at the central 
laboratory.
Nasal (midturbinate) swabs at the visits specified in the SoA will be obtained as one of the 
determinations for participants to be included in the evaluable immunogenicity analysis. 
These samples will be tested at the central laboratory using an RT-PCR test (Cepheid, an 
NAAT; FDA approved under EUA) to detect SARS-CoV-2.  Another determination for 
participants to be included in the evaluable immunogenicity analysis is the N-binding 
antibody assay.  Blood samples will be taken at visits specified in the SoA and analyzed at 
the central laboratory.  A positive result on either test will result in the immunogenicity data 
from that participant being excluded from the evaluable portion of the study population.  
However, administration of study intervention is not dependent on these test results, which 
will be available only after the study has ended.
8.1.1. Biological Samples
Blood and nasal swab samples will be used only for scientific research.  Each sample will be 
labeled with a code so that the laboratory 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.

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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.
The safety parameters also include reactogenicity e-diary reports of local reactions, systemic 
events (including fever), and use of antipyretic medication that occur in the 7 days after 
administration of the study intervention.  These prospectively self-collected occurrences of 
local reactions and systemic events are graded as described in Section 8.2.2.
8.2.1. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study.
See Section 10.5, Appendix 5, for suggested actions and follow-up assessments in the event 
of potential DILI.
8.2.2. 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 
antipyretic medication usage for 7 days from the day of administration of the study 
intervention.  The reactogenicity e-diary allows recording of these assessments only within a 
fixed time window, thus providing the accurate representation of the participant’s experience 
at that time.  Data on local reactions and systemic events reported in the reactogenicity 
e-diary will be transferred electronically to a third-party vendor, where they will be available 
for review by investigators and the Pfizer clinicians at all times via an internet-based portal.
At intervals agreed to by the vendor and Pfizer, these data will be transferred electronically 
into Pfizer's database for analysis and reporting.  These data do not need to be reported by the 
investigator in the CRF as AEs.
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 

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reactogenicity e-diary was completed.  The stop dates should be documented in the source 
documents and the information entered in the CRF.
8.2.2.1. 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.12
8.2.2.2. Local Reactions
During the reactogenicity e-diary reporting period, participants will be asked to assess 
redness, swelling, and pain at the injection site and to record the symptoms in the 
reactogenicity e-diary.  If a local reaction persists beyond the end of the reactogenicity 
e-diary period following vaccination, the participant 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 1.  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 1.
If a Grade 3 local reaction is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated.  Only an investigator or medically qualified person is able to classify a 
participant’s local reaction as Grade 4.  If a participant experiences a confirmed Grade 4 local 
reaction, the investigator must immediately notify the sponsor and, if it is determined to be 
related to the administration of the study intervention, further vaccinations will be 
discontinued in that participant.
Table 1.
Local Reaction Grading Scale
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially Life 
Threatening 
(Grade 4)
Pain at the 
injection site
Does not interfere 
with activity
Interferes with activity
Prevents daily 
activity 
Emergency room visit 
or hospitalization for 
severe pain
Redness
>2.0 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)
>10 cm 
(≥21 measuring 
device units)
Necrosis or exfoliative 
dermatitis
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

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8.2.2.3. Systemic Events
During the reactogenicity e-diary reporting period, participants will be asked to assess 
vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain, and new or 
worsened joint pain and to record the symptoms in the reactogenicity e-diary.  The symptoms 
will be assessed by the participant as absent, mild, moderate, or severe according to the 
grading scale in Table 2.
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.
Table 2.
Systemic Event Grading Scale
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially Life 
Threatening 
(Grade 4)
Vomiting
1-2 times in 
24 hours
>2 times in 
24 hours
Requires IV 
hydration
Emergency room visit 
or hospitalization for 
hypotensive shock
Diarrhea
2 to 3 loose stools 
in 24 hours
4 to 5 loose stools 
in 24 hours
6 or more loose stools 
in 24 hours
Emergency room visit 
or hospitalization for 
severe diarrhea
Headache
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe headache
Fatigue/tiredness
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe fatigue
Chills
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe chills
New or worsened 
muscle pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe new or worsened 
muscle pain
New or worsened 
joint pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe new or worsened 
joint pain
Abbreviation: IV = intravenous.
During the 7 days following each vaccination, potential COVID-19 symptoms that overlap 
with solicited systemic events (ie, fever, chills, new or increased muscle pain, diarrhea, 
vomiting) should be assessed by the investigator.

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If, in the investigator’s opinion, the symptoms are considered more likely to be vaccine 
reactogenicity, but a participant is required to demonstrate that he or she is
SARS-CoV-2–negative, a local SARS-CoV-2 test may be performed: if positive, the 
symptoms should be recorded as an AE rather than as systemic events in the reactogenicity 
e-diary.
8.2.2.4. 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 3 during analysis.
If a fever of ≥39.0°C (102.1°F) is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated.  Only an investigator or medically qualified person is able to confirm a 
participant’s fever as >40.0°C (>104.0°F).  If a participant experiences a confirmed fever 
>40.0°C (>104.0°F), the investigator must immediately notify the sponsor and, if it is 
determined to be related to the administration of the study intervention, further vaccinations 
will be discontinued in that participant.
Table 3.
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)
8.2.2.5. 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).
8.2.3. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Pregnancy tests will be performed in WOCBP at 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 

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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 and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
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).
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 (1-month follow-up).  In addition, any AEs occurring up to 48 hours after the blood 
draw and nasal swab collection at Visit 3 reported by the participant must be recorded in the 
CRF. SAEs will be collected from the time the participant provides informed consent 
through approximately 1 month after the last dose of study intervention (Visit 3).
For all participants receiving Dose 3, AEs and SAEs will be collected from the time the 
participant provides informed consent for the receipt of Dose 3 at Visit 101 through 
Visit 102.
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 and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.

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If a participant definitively 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 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.
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 Section 10.3.
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/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.

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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 towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are 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 exposure during pregnancy:

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 

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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 until 1 month 
after the last dose of study intervention.

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 ISF.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs.  If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly), the investigator should follow the procedures 
for reporting SAEs.  Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows:

Spontaneous abortion including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.

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8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.

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 ISF.
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
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE.  Such persons 
may include healthcare providers, family members, and other roles that are involved in the 
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE.  The information 
must be reported using the Vaccine SAE Reporting Form.  Since the information 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 is maintained in the ISF.
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.

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8.3.8. Adverse Events of Special Interest
This section provides information on AESIs that may be detected during the study:

Confirmed COVID-19 diagnosis (clinical signs/symptoms and positive SARS-CoV-2 
NAAT test)

A confirmed diagnosis of myocarditis or pericarditis. See Section 8.13 for additional 
procedures for monitoring of potential myocarditis or pericarditis.
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.
8.3.8.1. Lack of Efficacy
Lack of efficacy 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. 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 Safety only when associated with an SAE.
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.
8.5. Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
Genetics (specified analyses) are not evaluated in this study.

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8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Immunogenicity Assessments
Immunogenicity assessments are described in Section 8.1.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.11. Study Procedures
8.11.1. 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.
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 onward 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.

Perform a clinical assessment.  If the clinical assessment indicates that a physical 
examination is necessary to comprehensively evaluate the participant, perform a 
physical examination and record any findings in the source documents and, if 
clinically significant, record on the medical history CRF.

Measure the participant’s height and weight.

Ensure and document that all of the inclusion criteria and none of the exclusion 
criteria are met.

Measure the participant’s body temperature.

Perform urine pregnancy test on WOCBP as described in Section 8.2.3.

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
Discuss contraceptive use as described in Section 5.3.1.

Record nonstudy vaccinations as described in Section 6.5.

Collect a blood sample of approximately 20 mL for immunogenicity testing and to 
test for prior COVID-19.  Please refer to the ISF for further instructions.

Obtain a nasal (midturbinate) swab (collected by site staff) for determination of 
current SARS-CoV-2 status.  Please refer to the ISF for further instructions.

A blinded site staff member obtains the randomization number using the IRT system.  
An unblinded site staff member then enters the participant number (SSID) and 
randomization number to assign the study intervention allocation number.

Unblinded site staff member(s) will dispense/administer 1 dose of study intervention 
into the deltoid muscle of the (preferably) nondominant arm.  Please refer to the IP 
manual for further instruction on this process.

Blinded site staff must observe the participant for at least 30 minutes after study 
intervention administration for any acute reactions.  Record any acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of 
the CRF, and on an SAE form as applicable.

Explain the e-diary technologies available for this study (Section 8.2.2), 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 injection site measuring greater than 10 cm 
(>20 measuring device units).

Severe pain at the injection site.

Any severe systemic event.

Issue a measuring device to measure local reactions at the injection site and a 
thermometer for recording daily temperatures and provide instructions on their use.

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
Record AEs/SAEs as described in Section 8.3.

Ask the participant to contact the site staff or investigator if a medically attended 
event (eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Ask the participant to contact the site staff or investigator if he/she develops 
symptoms of a COVID-19 infection, as defined by the CDC,13 including:

New or increased cough;

New or increased shortness of breath;

Chills;

New or increased muscle pain;

New loss of taste/smell;

Sore throat;

Diarrhea;

Vomiting.

Schedule an appointment for the participant to return for the next study visit.

Remind the participant to bring the reactogenicity 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.
8.11.2. Visit 2 – Vaccination 2 (19 to 23 Days After Visit 1)

Record AEs/SAEs 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.

Perform urine pregnancy test on WOCBP as described in Section 8.2.3.

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
Discuss contraceptive use as described in Section 5.3.1.

Record nonstudy vaccinations as described in Section 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1
received by the participant if required for his or her clinical care.

Ensure and document that all of the inclusion criteria and none of the exclusion 
criteria are met.  If these eligibility criteria are not met, the participant may not 
receive further study intervention but will remain in the study to be evaluated for 
safety, immunogenicity, and efficacy (see Section 7).

A positive SARS-CoV-2 NAAT result without symptoms or a COVID-19 
diagnosis (signs/symptoms only or signs/symptoms and a positive SARS-CoV-2 
NAAT result) should not result in discontinuation of study intervention.

If study intervention (Dose 2) has been delayed per the criteria for temporary 
delay, because of febrile or other acute illness (Item 1, criteria for temporary 
delay), and the investigator later diagnoses the signs and symptoms as COVID-19 
(with or without a positive SARS-CoV-2 NAAT result), the participant should not 
be discontinued from any further doses of study intervention.

Measure the participant’s body temperature.

Ensure that the participant meets none of the temporary delay criteria as described in
Section 5.5.

Unblinded site staff member(s) will dispense/administer 1 dose of study intervention 
into the deltoid muscle of the (preferably) nondominant arm.  Please refer to the 
IP manual for further instruction on this process.

Blinded site staff must observe the participant for at least 30 minutes after study 
intervention administration for any acute reactions.  Record any acute reactions 
(including time of onset) in the participant’s source documents and on the AE page of 
the CRF, and on an SAE form as applicable.

Ensure the participant has a measuring device to measure local reactions at the 
injection site and a thermometer for recording daily temperatures.

Ensure the participant remains comfortable with the chosen e-diary platform, confirm 
instructions on 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 

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vaccination (where Day 1 is the day of vaccination) to determine if an unscheduled 
reactogenicity visit is required: 

Fever ≥39.0°C (≥102.1°F).

Redness or swelling at the injection site measuring greater than 10 cm 
(>20 measuring device units).

Severe pain at the injection site.

Any severe systemic event.

Ask the participant to contact the site staff or investigator if a medically attended 
event (eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Ask the participant to contact the site staff or investigator if he/she develops 
symptoms of a COVID-19 infection, as defined by the CDC,13 including:

New or increased cough; 

New or increased shortness of breath;

Chills;

New or increased muscle pain;

New loss of taste/smell;

Sore throat;

Diarrhea;

Vomiting.

Schedule an appointment for the participant to return for the next study visit.

Remind the participant to bring the reactogenicity 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.

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8.11.3. Visit 3 – 1-Month Follow-up (28 to 35 Days After Visit 2)

Record AEs/SAEs 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 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1
received by the participant if required for his or her clinical care.

Discuss contraceptive use as described in Section 5.3.1.

Collect a blood sample of approximately 20 mL for immunogenicity testing and to 
test for prior COVID-19.

Obtain a nasal (midturbinate) swab (collected by site staff) for determination of 
current SARS-CoV-2 status.

Collect the participant’s reactogenicity e-diary or assist the participant to remove the 
study application from his or her own personal device.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.11.4. Unscheduled Visits for a Grade 3 or Suspected Grade 4 Reaction
If a Grade 3 local reaction (Section 8.2.2.2), systemic event (Section 8.2.2.3), or fever 
(Section 8.2.2.4) 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 8.2.2.2), systemic event (Section 8.2.2.3), or fever 
(Section 8.2.2.4) is reported in the reactogenicity e-diary, a telephone contact or site visit 
should occur to confirm whether the event meets the criteria for Grade 4.
A site visit must be scheduled as soon as possible to assess the participant unless any of the 
following is true:

The participant is unable to attend the unscheduled visit.

The local reaction/systemic event is no longer present at the time of the telephone 
contact.

The participant recorded an incorrect value in the reactogenicity e-diary (confirmation 
of a reactogenicity e-diary data entry error).

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
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:

Measure body temperature (°F/°C).

Measure minimum and maximum diameters of redness (if present).

Measure minimum and maximum diameters of swelling (if present).

Assess injection site pain (if present) in accordance with the grades provided in 
Section 8.2.2.2.

Assess systemic events (if present) in accordance with the grades provided in 
Section 8.2.2.3.

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.
8.12. Study Procedures for Participants Who Accept the Offer to Receive Dose 3
8.12.1. Visit 101 – Vaccination 3 (At Least 90 Days After Visit 2)
Before Vaccination 3 and before any study-related procedures are performed, voluntary, 
written, study-specific informed consent will be obtained from the participant. Each 
signature on the ICD must be personally dated by the signatory. The investigator or his or 
her designee will also sign the ICD. A copy of the signed and dated ICD must be given to 
the participant. The source data must reflect that the informed consent was obtained before 
participation in the study.
It is anticipated that the procedures below will be conducted in a stepwise manner.

Confirm that the participant originally received lyophilized formulation of BNT162b2
at Vaccinations 1 and 2. Secondary confirmation by another site staff is required.

Measure the participant’s body temperature.

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
Perform urine pregnancy test on WOCBP as described in Section 8.2.3.

Discuss contraceptive use as described in Section 5.3.1.

Record nonstudy vaccinations as described in Section 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1
received by participant if required for his or her clinical care.

Review and consider inclusion criteria 2, 3, 4, and 5 and exclusion criteria.

Confirm that the participant meets all of the inclusion criteria and does not meet 
exclusion criteria 1, 3, 5, 6, 7, 10, 11, 12, 13, and 14.

Ensure that the participant does not meet any of the temporary delay criteria as 
described in Section 5.5.

Collect a blood sample of approximately 20 mL for immunogenicity testing. Please 
refer to the ISF for further instructions.

Obtain a nasal (midturbinate) swab (collected by site staff) for determination of 
current SARS-CoV-2 status. Please refer to the ISF for further instructions.

Obtain the participant’s vaccine allocation vial using the IRT system.

Dispense/administer 1 dose of study intervention into the deltoid muscle of the 
(preferably) nondominant arm. Please refer to the IP manual for further instruction 
on this process.

Observe the participant for at least 30 minutes after study intervention administration 
for any acute reactions. Record any acute reactions (including time of onset) in the 
participant’s source documents and on the AE page of the CRF, and on an SAE form 
as applicable.

Issue a measuring device to measure local reactions at the injection site and a 
thermometer for recording daily temperatures and provide instructions on their use.

Remind the participant of the e-diary technologies available for this study 
(Section 8.2.2), 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.

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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 injection site measuring greater than 10 cm 
(>20 measuring device units).

Severe pain at the injection site.

Any severe systemic event.

Record AEs/SAEs as described in Section 8.3.

Ask the participant to contact the site staff or investigator if a medically attended 
event (eg, doctor’s visit, emergency room visit) or hospitalization occurs.

Ask the participant to contact the site staff or investigator if he/she develops 
symptoms of a COVID-19 infection, as defined by the CDC,13 including:

New or increased cough; 

New or increased shortness of breath;

Chills;

New or increased muscle pain;

New loss of taste/smell;

Sore throat;

Diarrhea;

Vomiting.

Schedule an appointment for the participant to return for the next study visit.

Remind the participant to bring the reactogenicity 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.

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The investigator or appropriately qualified designee reviews the reactogenicity e-diary data 
online following vaccination to evaluate participant compliance and as part of the ongoing 
safety review. Daily review is optimal during the active diary period.
8.12.2. Visit 102 – 1-Month Follow-up (28 to 35 Days After Visit 101)

Record AEs/SAEs 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 6.5.

Record details of any of the prohibited medications specified in Section 6.5.1
received by the participant if required for his or her clinical care.

Discuss contraceptive use as described in Section 5.3.1.

Collect a blood sample of approximately 20 mL for immunogenicity testing.

Obtain a nasal (midturbinate) swab (collected by site staff) for determination of 
current SARS-CoV-2 status. Please refer to the ISF for further instructions.

Collect the participant’s reactogenicity e-diary or assist the participant to remove the 
study application from his or her own personal device.

Complete the source documents.

The investigator or an authorized designee completes the CRFs.
8.13. 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 of 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

Troponin level
If myocarditis or pericarditis are suspected based upon the initial evaluation, the following 
should also be performed:

Cardiac echocardiogram, and/or

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
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.
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The estimands corresponding to each primary and secondary objective are described in the 
table in Section 3.
The estimands to evaluate the immunogenicity objectives are based on the evaluable 
immunogenicity population (Section 9.3).  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 groups, since the impact of noncompliance is likely to diminish the 
observed difference between the 2 groups.  Missing antibody results will not be imputed.  
Immunogenicity results that are below the LLOQ will be set to 0.5 × LLOQ in the analysis; 
this may be adjusted once additional data on the assay characteristics become available.
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.
9.1.2. Statistical Hypothesis
The primary immunogenicity objective is to assess the noninferiority of the immune response 
induced by lyophilized SDV compared to frozen-liquid MDV BNT162b2. The null 
hypothesis (H0) is
H0: ln(μ1) – ln(μ2) ≤ ln(0.67) vs H1: ln(μ1) – ln(μ2) > ln(0.67)
where ln(0.67) corresponds to a 1.5-fold margin for noninferiority and 

ln(μ1) is the natural log of the geometric mean of full-length S-binding IgG levels 
measured 1 month after Dose 2 from participants receiving lyophilized SDV 
BNT162b2;

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ln(μ2) is the natural log of the geometric mean of full-length S-binding IgG levels 
measured 1 month after Dose 2 from participants receiving frozen-liquid MDV 
BNT162b2 control for lyophilized SDV 
Noninferiority will be declared if the lower bound of the 2-sided 95% CI for the GMR of 
lyophilized SDV relative to the corresponding frozen-liquid MDV control is greater than 
0.67 (1.5-fold criterion).
9.1.3. Multiplicity Considerations
There is only 1 hypothesis for the primary immunogenicity endpoint, and within-group 
descriptive summaries will be provided for the secondary immunogenicity endpoint.  
Consequently, no multiplicity adjustments are applied.
9.2. Sample Size Determination
The sample size in Part 1 of the study is based on the noninferiority evaluation for the 
primary immunogenicity endpoint, full-length S-binding IgG levels 1 month after Dose 2, 
using a 1.5-fold noninferiority margin for the comparison between lyophilized SDV 
BNT162b2 relative to frozen-liquid MDV BNT162b2. The second part of the study for 
assessing the immune responses induced by frozen-liquid BNT162b2 with LNP size at the 
upper end of specification or RTU BNT162b2 is for descriptive purposes; thus, sample size 
for this part is not based on statistical considerations.
Common assay standard deviations from each group are assumed to be 0.6456 based on 
results from Phase 1 of Study C4591001 (BNT162b2 30 µg, 18- to 55-year age group). With 
this standard deviation and the observed GMT difference assumed in the power analysis 
below, a sample size of 220 evaluable participants per group in Part 1 of the study will 
provide a power of 90.1% to declare noninferiority of lyophilized BNT162b2 to frozen-liquid 
MDV for the primary objective (Table 4).
Assuming a nonevaluable rate of 20%, the study will randomize approximately 
275 participants to each group in Part 1 of the study to achieve the required number of 
evaluable participants.
Table 4.
Power Analysis for Noninferiority Assessment
Criteria
Standard Deviation 
(Log Value)a
Assumed Observed 
GMT Difference 
(Log Scale)
Number of Evaluable 
Participants per 
Group
Powerb
Lower limit of 95% CI for 
GMR (lyophilized SDV 
BNT162b2/frozen-liquid 
MDV BNT162b2) >0.67
0.6456
-0.2
220
90.1%
Abbreviations: GMR = geometric mean ratio; GMT = geometric mean titer; MDV = multidose vial; 
SDV = single-dose vial.
a.
Reference: BNT162b2 (30 µg), 18- to 55-year age group (C4591001 Phase 1, N=12).  Calculation may be 
updated if additional information becomes available to better estimate the standard deviation.
b.
At the 0.05 alpha level (2-sided).

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9.3. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set
Description
Enrolled
All participants who have a signed ICD.
Randomized
All participants who are assigned a randomization number in 
the IWR system.
Evaluable immunogenicity
All eligible randomized participants who receive 2 doses of 
the vaccine to which they are randomized with Dose 2 
received within the predefined window, have at least 1 valid 
and determinate immunogenicity result from the blood sample 
collected within an appropriate window at 1 month after the 
Dose 2 visit, are negative for SARS-CoV-2 infection during 
the study, and have no other important protocol deviations as 
determined by the clinician.
Dose 3 evaluable 
immunogenicity
All eligible randomized participants who receive 2 doses of 
lyophilized formulation of BNT162b2 to which they are 
randomized, with Dose 2 received within the predefined 
window, receive a third dose of frozen-liquid BNT162b2 
formulation, have at least 1 valid and determinate 
immunogenicity result from the blood sample collected within 
an appropriate window at the 1-month post–Dose 3 visit, are 
negative for SARS-CoV-2 infection during the study, and 
have no other important protocol deviations as determined by 
the clinician.
All-available 
immunogenicity
All participants who receive at least 1 dose of the study 
intervention and have at least 1 valid and determinate 
immunogenicity result after vaccination.
Safety
All randomized participants who receive at least 1 dose of the 
study intervention.
9.4. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data.  
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.4.1. General Considerations
Unless stated otherwise, “vaccine group” in this section refers to participants receiving 
lyophilized SDV, frozen-liquid MDV control for lyophilized SDV, frozen-liquid BNT162b2 
with LNP size at the upper end of specification, or RTU BNT162b2.  CIs for all endpoints in 

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the statistical analysis will be presented as 2-sided at the 95% level unless specified 
otherwise.
For all the immunogenicity endpoints, the analysis will be based on the evaluable 
immunogenicity population or Dose 3 evaluable immunogenicity population. An additional 
analysis will 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.
The safety analyses will be based on the safety population.  Participants will be summarized 
by vaccine group according to the study interventions they actually received.
9.4.1.1. Analysis for Binary Data
Descriptive statistics for categorical variables (eg, proportions) are the percentage (%), the 
numerator (n) and the denominator (N) used in the percentage calculation, and the 95% CIs 
where applicable.
The exact 95% CI for binary endpoints for each group will be computed using the 
F distribution (Clopper-Pearson).
9.4.1.2. Analysis for Continuous Data
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
standard deviation, minimum, and maximum.
9.4.1.2.1. Geometric Mean Ratios
The GMRs will be calculated as the mean of the difference of logarithmically transformed 
assay results between 2 vaccine groups and exponentiating the mean.  Two-sided CIs will be 
obtained by calculating CIs using Student’s t-distribution for the mean difference of the 
logarithmically transformed assay results and exponentiating the confidence limits.
9.4.1.2.2. Geometric Means
The geometric means will be calculated as the mean of the assay results after making the 
logarithmic 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.
9.4.1.2.3. Geometric Mean Fold Rises
GMFRs are defined as ratios of the results after vaccination to the results before vaccination.  
GMFRs are limited to participants with nonmissing values at both time points.
GMFRs will be calculated as the mean of the difference of logarithmically transformed assay 
results (later time point minus earlier time point) and exponentiating the mean.  The 
associated 2-sided 95% CIs will be obtained by constructing CIs using Student’s 

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t-distribution for the mean difference on the logarithm scale and exponentiating the 
confidence limits.
9.4.1.2.4. Reverse Cumulative Distribution Curve
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.
9.4.2. Primary Endpoint(s)
Endpoint
Statistical Analysis Methods
Immunogenicity
GMR of full-length S-binding IgG levels in participants receiving lyophilized 
SDV BNT162b2 compared to frozen-liquid MDV BNT162b2 control for 
lyophilized SDV
For full-length S-binding IgG levels, the GMR at 1 month after Dose 2 will be 
provided along with associated 2-sided 95% CIs (see Section 9.4.1.2.1).
Noninferiority will be declared if the lower limit of the 2-sided 95% CI for the GMR 
is greater than 0.67.
Safety
Descriptive statistics will be provided for each reactogenicity endpoint for each dose 
and 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 9.4.1.1).
AEs and SAEs will be categorized according to MedDRA terms.  Counts, 
percentages, and the associated Clopper-Pearson 95% CIs of AEs and SAEs from 
Dose 1 through 1 month after Dose 2 will be provided for each vaccine group.
9.4.3. Secondary Endpoint(s)
Endpoint
Statistical Analysis Methods
Immunogenicity
GMCs of full-length S-binding IgG levels
For full-length S-binding IgG levels, GMCs and 2-sided 95% CIs will be provided for 
each vaccine group in Part 1 of the study (lyophilized BNT162b2 in SDVs and 
frozen-liquid BNT162b2 in MDVs) at baseline (before Dose 1) and at 1 month after 
Dose 2.
Statistical methods are described in Section 9.4.1.2.2.
GMFRs of full-length S-binding IgG levels
For full-length S-binding IgG levels, the GMFRs and 2-sided 95% CIs will be 
provided for each vaccine group in Part 1 of the study (lyophilized BNT162b2 in 
SDVs and frozen-liquid BNT162b2 in MDVs) from baseline (before Dose 1) to
1 month after Dose 2.

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Endpoint
Statistical Analysis Methods
GMFRs will be limited to participants with nonmissing values prior to the first dose 
and at the postvaccination time point. The statistical methods are described in 
Section 9.4.1.2.3.
9.4.4. Exploratory Endpoint(s)
Endpoint
Statistical Analysis Methods
Safety 
Descriptive statistics will be provided for each reactogenicity endpoint in participants 
who originally received 2 doses of lyophilized formulation of BNT162b2 and 
received frozen-liquid BNT162b2 formulation as a third dose. Local reactions and 
systemic events from Day 1 through Day 7 after the third dose (where Day 1 is the 
day of the third dose) 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 9.4.1.1).
AEs and SAEs will be categorized according to MedDRA terms. Counts and
percentages of participants with AEs and SAEs from Dose 3 through 1 month after 
Dose 3 will be provided, along with the associated Clopper-Pearson 95% CIs.
Immunogenicity
GMR of frozen-liquid BNT162b2 with LNP size at the upper end of specification
relative to frozen-liquid BNT162b2 in MDVs at 1 month after Dose 2
For full-length S-binding IgG levels and/or SARS-CoV-2 neutralizing titers, the GMR 
at 1 month after Dose 2 will be provided along with associated 2-sided 95% CIs (see 
Section 9.4.1.2.1). For the analysis of full-length S-binding IgG levels, all available 
IgG data for participants receiving frozen-liquid BNT162b2 in MDVs from Part 1 will 
be used. For the analysis of SARS-CoV-2 neutralizing titers, a random sample of 
approximately 30 age-matched participants receiving frozen-liquid BNT162b2 in 
MDVs will be selected from Part 1 of the study.
GMCs of full-length S-binding IgG levels and/or GMTs of SARS-CoV-2
neutralizing titers
For full-length S-binding IgG levels and/or SARS-CoV-2 neutralizing titers, 
GMCs/GMTs and 2-sided 95% CIs will be provided for each vaccine group in Part 2 
of the study (frozen-liquid BNT162b2 with LNP size at the upper end of specification 
and RTU formulation) at baseline (before Dose 1) and at 1 month after Dose 2.
Statistical methods are described in Section 9.4.1.2.2.
GMFRs of full-length S-binding IgG levels and/or SARS-CoV-2 neutralizing 
titers
For full-length S-binding IgG levels, the GMFRs and 2-sided 95% CIs will be 
provided for each vaccine group in Part 2 of the study (frozen-liquid BNT162b2 with 
LNP size at the upper end of specification and RTU formulation) from baseline 
(before Dose 1) to 1 month after Dose 2.

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Endpoint
Statistical Analysis Methods
GMFRs will be limited to participants with nonmissing values prior to the first dose 
and at the postvaccination time point. The statistical methods are described in 
Section 9.4.1.2.3.
GMCs of full-length S-binding IgG levels and/or GMTs of SARS-CoV-2 
neutralizing titers for participants receiving the third dose
For full-length S-binding IgG levels and/or SARS-CoV-2 neutralizing titers, 
GMCs/GMTs and 2-sided 95% CIs will be provided for Dose 3 evaluable 
immunogenicity participants at baseline (before Dose 1), 1 month after Dose 2, prior 
to Dose 3, and 1 month after Dose 3.
Statistical methods are described in Section 9.4.1.2.2.
GMFRs of full-length S-binding IgG levels and/or SARS-CoV-2 neutralizing 
titers for participants receiving the third dose
For full-length S-binding IgG levels and/or SARS-CoV-2 neutralizing titers, the 
GMFRs from prior to Dose 3 to 1 month after Dose 3 and 2-sided 95% CIs will be 
provided for participants receiving the third dose.
GMFRs will be limited to participants with nonmissing values prior to Dose 3 and at 
1 month after Dose 3. The statistical methods are described in Section 9.4.1.2.3.
9.5. Interim Analyses
No formal interim analysis will be conducted for this study. Statistical analyses will be 
carried out when the final data for specified objectives for a given study part are available 
while the study is ongoing.
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will use a DMC.  The DMC is independent of the study team and includes 
external members.  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.  This may include, but is not limited to:

Contemporaneous review of related AEs up to 1 month after completion of the 
vaccination schedule,

Contemporaneous review of all SAEs up to 1 month after completion of the 
vaccination schedule.
The recommendations made by the DMC to alter the conduct of the study will be forwarded 
to the appropriate Pfizer personnel for final decision.  Pfizer will forward such decisions, 
which may include summaries of aggregate analyses of safety data, to regulatory authorities, 
as appropriate.

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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 and 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.
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 guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.
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 ICH GCP that the investigator becomes aware 
of.

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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 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, HIPAA requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data.
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date 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 ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant.  Participants who are rescreened 
are required to sign a new ICD.

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Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research.  The optional 
additional research does not require the collection of any further samples.  The investigator 
or authorized designee will explain to each participant the objectives of the additional 
research.  Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period.
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 identification. 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. 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.

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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.
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 available data from these trials 
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.
10.1.6. 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.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.

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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.
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 (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, remote, or on-site monitoring), are provided in the
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
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, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.

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10.1.7. 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 can be found in the study monitoring plan.
Description of the use of computerized system is documented in the data management plan.
10.1.8. 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 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 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.

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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.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first.
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission.  This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer intervention-
related information necessary for the appropriate scientific presentation or understanding of 
the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
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.
10.1.10. 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
or other electronic system.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention
identifiers, participant numbers, contact information for the investigator site, and contact 
details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.  The contact number 
can also be used by investigator staff if they are seeking advice on medical questions or 

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problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  The contact number is not intended for use by the participant directly, 
and if a participant calls that number, he or she will be directed back to the investigator site.
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 2/19-23 days after Visit 1) as well as at 
Visit 101 for participants receiving Dose 3.

Pregnancy test (β-hCG): Local urine testing will be standard for the protocol unless 
serum testing is required by local regulation or IRB/EC for female participants of 
childbearing potential.
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.  Investigators must document their review of each 
laboratory safety report.

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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 conditions 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/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 which 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 SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (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.

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Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent 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) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 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.

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 patient 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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10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF and 
for reporting serious adverse events on the Vaccine SAE Reporting Form to Pfizer Safety.  
These requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious adverse 
events (AEs); and (3) exposure to the study intervention under study during pregnancy or 
breastfeeding, and occupational exposure.
It should be noted that the Vaccine SAE Reporting Form for reporting of SAE information 
is not the same as the AE page of the CRF.  When the same data are collected, the forms 
must be completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the Vaccine SAE 
Reporting Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the Vaccine
SAE Reporting Form to 
Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is not 
recorded.
All (and EDP supplemental 
form for EDP)
Note:  Include all SAEs 
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.

When an AE/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/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/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 

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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/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories:
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.

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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

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.

The investigator will use clinical judgment to determine the relationship.

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/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor.  In addition, if the investigator determines that 
an SAE is associated with study procedures, the investigator must record this causal 
relationship in the source documents and CRF, and report such an assessment in the 
dedicated section of the Vaccine SAE Reporting Form and in accordance with the 
SAE reporting requirements.

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Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via 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 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 with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent.
OR

Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.

In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.4).
10.4.2. Female Participant Reproductive Inclusion Criteria
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.

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10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to 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.

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.

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10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner:

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential 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;

Injectable.
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.

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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 an “adaptor” 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 cases of 
Hy’s law, 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, 
supplement (herbal) use and consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and potential occupational exposure to chemicals, should be collected.  
Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary 
tract) 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: 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
-hCG
beta-human chorionic gonadotropin
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
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
clinical study report
DILI
drug-induced liver injury
DMC
data monitoring committee
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
e-diary
electronic diary
EDP
exposure during pregnancy
EMA
European Medicines Agency
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
GMR
geometric mean ratio
GMT
geometric mean titer
HBV
hepatitis B virus

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Abbreviation
Term
HCV
hepatitis C virus
HIPAA
Health Insurance Portability and Accountability Act
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
ISF
investigator site file
IWR
interactive Web-based response
JCVI
Joint Committee on Vaccination and Immunisation
LFT
liver function test
LLOQ
lower limit of quantitation
LNP
lipid nanoparticle
lyo
lyophilized
MDV
multidose vial
MedDRA
Medical Dictionary for Regulatory Activities
MERS
Middle East respiratory syndrome
modRNA
nucleoside-modified messenger ribonucleic acid
N
SARS-CoV-2 nucleoprotein
N/A
not applicable
NAAT
nucleic acid amplification test
NIMP
noninvestigational medicinal product
P2 S
SARS-CoV-2 full-length, P2 mutant, prefusion spike glycoprotein
PI
principal investigator
PPE
personal protective equipment
PT
prothrombin time
PVC
premature ventricular contraction/complex
RCDC
reverse cumulative distribution curve
RNA
ribonucleic acid
RSV
respiratory syncytial virus
RT-PCR
reverse transcription–polymerase chain reaction
RTU
ready-to-use

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Abbreviation
Term
S
spike protein
S1
spike protein S1 subunit
SAE
serious adverse event
SAP
statistical analysis plan
SARS
severe acute respiratory syndrome
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SDV
single-dose vial
SSID
single subject identifier
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
Th 1
T-helper type 1
UK
United Kingdom
ULN
upper limit of normal
US
United States
VAED
vaccine-associated enhanced disease
WHO
World Health Organization
WOCBP
woman/women of childbearing potential

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11. REFERENCES
1
Virus Pathogen Resource (ViPR). Strain details for severe acute respiratory syndrome-
related coronavirus strain Wuhan-Hu-1. Available from: 
https://www.viprbrc.org/brc/viprStrainDetails.spg?ncbiAccession=MN908947&decorat
or=corona.  Accessed: 11 Aug 2020.
2
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PF-07302048 (BNT162b2 RNA-Based COVID-19 Vaccine)
Protocol C4591020
Final Protocol Amendment 2, 13 Sep 2021
PFIZER CONFIDENTIAL
Page 96
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