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PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 1A PHASE 1/2 /3, PLACEBO -CONTROLLED , RANDOMIZED, OBSERV ER-BLIND, 
DOSE -FINDING STUDY T O EVALUATE THE SAFETY, TOLERABI LITY, 
IMMUNOGENICITY, AND EFFICACY OF SARS -COV -
2RNA VACCINE 
CANDIDATES AGAINST C OVID -19 IN HEALTHY INDIVIDUALS
Study Sponsor: BioNTech
Study Conducted By: Pfizer
Study Intervention Number: PF-07302048
Study Intervention Name: RNA -Based COVID -19 Vaccine s
US IND Number: 19736
EudraCT Number: 2020- 002641- 42
Protocol Number: C4591001
Phase: 1/2/3
Short Title: A Phase 1/2 /3Study  to Evaluate the Safety , Tolerabilit y, Immunogenicity, and 
Efficacy  of RNA Vaccine Candidates Against C OVID-19 in Healthy  Individuals
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these document s, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by app licable law ) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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FDA-CBER-2021-5683-0014054
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 2Protocol Amendment Summary of Changes Table
Document History
Document Version Date Summary and Rationale for Changes
Protocol amendment 9 29October 2020 To better align with the natural history of 
SARS -CoV- 2 infection , added Phase 2/3 
secondary efficacy objectives, estimand s,and 
endpoint sto include COVID -19 cases that occur 
from 14 days after the second dose ; also 
modified the existing secondary efficacy 
objectives, estimands, and endpoints to include 
COVID -19 cases that occur from 14 days , as 
well as 7 days ,after the second dose;
Made corresponding changes to the study 
design, study assessments and procedures, 
andstatistical analysis section s.
For operational reasons ,removed the interim 
analysis planned after accrual of 32 cases.
Clarified that interim analyses will be conducted 
after accrual of at least 62, 92, and 120 cases .
Included any participants 16 through 17 years of 
age enrolled under this amendment in the 
reactogenicity subset .
Added an unblinded clinical scientist to support 
DMC activities.
Clarified that s erology data after a postbaseline 
positive SARS -CoV- 2 test r esult will not be 
included in the analysis based on theevaluable 
immunogenicity population s.
Protocol amendment 8 15 October 2020 Removed “N-binding antibody ”and 
“SARS -CoV- 2 detection by NAAT ”as 
endpoints from the third exploratory objective , 
as these results are used for the determination of 
the population, and are not endpoints.
Clarified that the “Process 1” participants 
included in the descriptive analysis of 
“Process 1”-and “Process 2”- manufactured 
study intervention swill be selected randomly .
Clarified that surveillance of potential 
COVID -19 symptoms should continue even if a 
participant has a positive SARS -CoV- 2 test 
earlier in the study.
Further modified the circumstances in which a 
local NAAT result may be used in the 
COVID -19 case definition.
Clarified that f or participants who are not in the 
reactogenicity subset, local reactions and 
systemic events following vaccination should be 
detected and reported as AEs .
Clarified that premenarchal females are not 
WOCBP.
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FDA-CBER-2021-5683-0014055
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 3Document History
Document Version Date Summary and Rationale for Changes
Made various editorial changes .
Protocol amendment 7 06 October 2020 Reduced the lower age range to include 
adolescents 12 to 15 years of age and added 
corresponding objectives.
Removed reference to COVID -19 antibody 
testing in Section 2.3.2 .
Clarified w ithefficacy estimands and endpoints 
that last dose refers to second dose.
Added an additional exploratory objective to 
describe safety and immunogenicity in 
participants 16 to 55 years of age vaccinated 
with study intervention produced by 
manufacturing “Process 1” or “Process 2.”
Clarified exclusion criterion 5.
Added Section 6.1.1 to describe manufacturing 
“Process 1” and “Process 2.”
Clarified the degree of unblinding on the 
unblinded submissions team in Section 6.3.3 .
Made provision for a second dose of BNT162b2 
in participants who were affected by a 
medication error at Visit 2 in Section 6.6.
Provided further clarification regarding 
discontinuation of study intervention in 
Section 7.1.
Modified the circumstances in which a local 
NAAT result may be used in the COVID -19 
case definition.
Added that 2 periods of potential COVID -19 
symptoms within 4 days will be considered as a 
single illness.
Provided guidance in Section 8.13 regarding 
circumstances in which a SARS -CoV- 2 test 
might be required even if s ymptoms within 7 
days following each vaccination are considered 
more likely due to vaccine reactogenicity.
Made allow ance in Section 8.13 for a second 
SARS -CoV- 2 test to be performed within the 
same potential COVID -19 illness if it is in 
accordance w ith ro utine practice.
Added Section 8.15 to describe the reporting of 
SARS -CoV- 2 test results and their implications 
for participants receiving a second vaccine dose.
Added statistical hypothesis and pow er analysis 
for evaluation of noninferiority of the immune 
response to BNT162b2 in participants 12 to 15 
years of age to the response in participants 16 to 
25 years of age.
Amended scope of analyses of safety data in 
Section 9.5.1 .
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FDA-CBER-2021-5683-0014056
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 4Document History
Document Version Date Summary and Rationale for Changes
Made various editorial changes.
Protocol amendment 6 
(Germ any-specific)23 Septemb er 2020 According to regulatory request, inclusion 
criterion 1 now  specifies that participants less 
than 18 years of age will not be enrolled in the 
EU.
Protocol amendment 6 08 September 2020 Reordered some procedures in the Phase 2/3 
schedule of activities for consistency with the 
main body of the protocol.
Corrected the w indow  for the 6 -month follow -up 
visit to be approximately 6 months after 
Vaccination 2.
Reduced the volume of blood draw s to ~20 mL.
Removed the need to have safety data reported
for participants to be included in the safety 
objective assessment.
Added an exploratory objective to describe 
safety, immunogenicity, and efficacy in 
participants with stable HIV disease.
Increased the sample size for Phase 2/3 to 
~43,998.
Clarified that inclusion criterion 4 (ie, 
participants at higher risk for acquiring COVID -
19) is applicable for Phase 2/3 only, and 
provided some examples.
Removed exclusion criterion 2 (ie, known 
infection with HIV, HCV, or HBV) for Phase 3 
and added criteria for HIV -positive participants.
Decreased the low er age limit and removed the 
upper age limit for inclusion in Phase 2/3 in 
order to evaluate BNT162b2 30 µg in older 
adolescents and those over 85 years of age; 
updated the title and other references to adults to 
align with this change.
Renamed the immunological assays to align 
with other program -level documents.
Removed reference to the SARS -CoV -2 full -
length, P2 mutant, prefusion spike glycoprotein 
(P2 S) being “heads up .”
Clarified that a positive SARS -CoV -2 NAAT 
result without symptoms should not result in 
discontinuation of study intervention.
Added clarification that p otential COVID -19 
illnesses that are consistent with the clinical 
endpoint definition should notbe recorded as 
AEs.
Updated the analysis population descriptions to 
align with the study SAP.
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FDA-CBER-2021-5683-0014057
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 5Document History
Document Version Date Summary and Rationale for Changes
Protocol amendment 5 24 July 2020 Follow ing regulatory feedback:
Renamed Stage 1 to Phase 1, removed Stage 2, 
and renamed Stage 3 to Phase 2/3.
Clarified that a single vaccine candidate, 
administered as 2 doses 2 1 days apart, will be 
studied in Phase 2/3.
Stated that the vaccine candidate selected for 
Phase 2/3 evaluation is BNT162b2 at a dose of 
30µg.
Removed the potential to study BNT162b3.
Immunogenicity data will be summarized for the 
first 360 participants t hrough 1 month after Dose 
2, rather than through 21 days after Dose 1.
Provided further details of sponsor staff that will 
be unblinded in Phase 2/3.
Clarified which stopping rules apply to which 
phase of the study.
In addition:
Clarified the AE reporting requirements for 
potential COVID -19 illnesses.
Updated that Visit 1 may be conducted across 2 
consecutive days in Phase 2/3.
Moved the immunogenicity objectives in 
Phase 2/3 to become exploratory.
Added an additional inclusion criterion to enroll 
particip ants who, in the judgment of the 
investigator, are at risk for acquiring COVID -19.
Modified exclusion criterion 5, so that 
participants with a p revious clinical or 
microbiological diagnosis of COVID -19are 
excluded from all phases of the study.
Clarified that there will be 2 all -available 
efficacy populations.
Clarified that immunogenicity samples will be 
draw n for all participants; analyses will be based 
upon results from subsets of samples, according 
to the purpose.
Updated that the 3 -tier approach to su mmarizing 
AEs will only be performed in Phase 2/3.
Updated that at each interim analysis for 
efficacy, only the first primary objective w ill be 
evaluated.
Changed to use the same posterior probability 
(99.5%) for all interim analyses, resulting in 
case spl it changes in T ables 5, 6, and 7 .
Updated the s topping and alert ruleparameter s 
for enhanced COVID -19.
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FDA-CBER-2021-5683-0014058
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 6Document History
Document Version Date Summary and Rationale for Changes
Protocol amendment 4 30 June 2020 Given the rapidly evolving pandemic situation, and 
the need to demonstrate VE as soon as possible, the 
protocol has been amended to be pow ered to meet 
new efficacy objectives. These new efficacy 
objectives and corresponding endpoints have been 
added to Section 3.
Further nonclinical data are available to support the 
study of the BNT162b3 candidate in humans, and the 
candidate has been added to the protocol.
The 6 -month safety follow -up telephone contact has 
been changed to an in -person visit for Stage 3 
participants, to allow  collection of an 
immunogenicity blood sample.
The COVID- 19 illness visit has now added 
flexib ility to permit a remote or in -person visit.
The COVID- 19 illness symptoms have been updated 
to align with the FDA- accepted definitions; this 
change is also reflected in the criteria for temporary 
delay of enrollment.
AEs that occur between consent and d osing will now 
be reported on the AE (rather than Medical History) 
CRF, to align with the latest Pfizer protocol 
template.
Changes have been made to the headings to align 
with the latest Pfizer protocol template.
Clarified that only an unblinded site staff member 
may obtain the participant’s randomization number 
and study intervention allocation. 
Additional interim analyses have been added to 
evaluate VE and futility during the study.
As a result of regulatory feedback, an appendix has 
been added to outline the stopping and alert rules to 
monitor for potential enhanced COVID -19.
Protocol amendment 3 10 June 2020 As data have become available from this study and 
the BNT162 -01 study in Germany, the following 
decisions were made:
Not to study the BNT162 a1 and BNT162c2 
vaccine candidates at this time.  Therefore, these 
candidates have been removed from the 
protocol.
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FDA-CBER-2021-5683-0014059
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 7Document History
Document Version Date Summary and Rationale for Changes
To study further low er dose levels of the 
modRNA candidates.  Therefore, a 20 -µg dose 
level is formally included for BNT162b1 and 
BNT162b2.
To permit individual and group dosing 
alterations for the second dose of study 
intervention.
Follow ing regulatory feedback, the BNT162b3 
vaccine candidate has been removed from the 
protocol until further nonclinical data are available to 
support study in h umans.
Given the rapidly evolving pandemic situation, 
additional blood draws for exploratory COVID -19 
research , intended to establish a n immunological 
surrogate of protection, will be taken from selected 
participants who consent.
In order to increase flexibility enrolling participants , 
an extended screening window (increased from 14 to 
28 days) for sentinel participants in Stage 1 has been 
added.  This is considered acceptable since eligible 
participants are expected to be either h ealthy or have 
stable medical conditions .
To increase the number of doses that can be obtained 
from available vaccine vials, not all dose levels will 
result in a dosing volume of 0.5 mL.  Precise dosing 
instructions will be provided in the IP manual.
To facilitate the reporting of COVID -19 illness 
diagnoses and potential symptoms to the 
investigator, participants may utilize a COVID -19 
illness e -diary.
Protocol amendment 2 27 May 2020 Given the urgent nature of the pandemic situation, 
the following chang es allow determin ation of the 
appropriate human dose level for both younger and 
older adults to move speedily into the next phase of 
clinical evaluation :
Added a new vaccine candidate, BNT162b3, 
modRNA encoding a membrane- anchored RBD
Added a 50 -µg dose level for vaccine candidates 
based on the modRNA platform (ie, BNT162b1, 
BNT162b2, and BNT162b3)
Modified the criteria required for the IRC to 
determine dose escalation in the 18 -to 55 -year 
age cohort and advancement to groups of 
participants 65 to 85 years of age
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FDA-CBER-2021-5683-0014060
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 8Document History
Document Version Date Summary and Rationale for Changes
In addition:
Removed hemoglobin change -from -baseline 
abnormalities from the laboratory abnormality 
grading scale as abnormalities should be graded 
based upon absolute values
Protocol amendment 1 13 May 2020 Follow ing regulatory feedback:
Modified exclusion criteria and prohibited 
inhaled/nebulized corticosteroids for sentinel 
participants in Stage 1
Clarified that the rapid test for prior COVID -19 
infection for sentinel participants in Stage 1 will 
be used only for screening purposes
Removed time frames for stopping rules
Stated that d ata supporting the selection of 
vaccine candidate(s)/dose level(s) and 
schedule(s) for Stages 2 and 3 will be submitted 
to the FDA for review
Follow ing preliminary experience in the 
BioNTech study conduc ted in Germany 
(BNT162 -01):
Decreased the dose levels for BNT162a1 and 
BNT162c2
Additionally:
Clarified the roles of BioNTech and Pfizer
Amended text so that the IRC decision to 
progress group(s) into Stages 2 and 3 can be 
based upon safety and immunogeni city data 
after Dose 1 or 2
Clarified safety data requirements to permit dose 
escalation
Amended text so that the progression to 
participants 65 to 85 years of age can be based 
upon data from the same RNA platform
Incorporated a protocol administrative cha nge to 
correct the variant designation and the encoded 
antigen to BNT162c2
Clarified that the SARS -CoV -2 neutralizing 
assay does not employ wild -type virus
Clarified that the SARS -CoV -2 spike protein –
binding antibody assay is specific for the S1 
subunit
Clarified that efficacy against COVID -19 is 
based upon illness (not infection) rate ratio
Incorporated a protocol administrative change to 
state that the study placebo may be supplied in a 
glass or plastic vial
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FDA-CBER-2021-5683-0014061
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 9Document History
Document Version Date Summary and Rationale for Changes
Corrected a typographical error in Section 6.5.1 
regarding the time frame for prior receipt of 
blood/plasma products or immunoglobulins
Corrected a typographical error in Table 2 
regarding the lower limit of diameter (cm) for 
mild redness and swelling
Updated the °C fever scale in Table 4 to ensure 
that all potential °F values are correctly assigned
Incorporated a protocol administrative change to 
clarify that a rapid test for prior COVID -19 
infection will be performed for s entinel 
participants in Stage 1 , and a serum sample will 
be drawn for potenti al future assessment
Clarified that, after screening, physical 
examinations in s entinel participants in Stage 1
will be directed
Clarified the descriptions of the populations for 
analysis to align with the statistical analysis plan
Added a com plete safety and immunogenicity 
analysis approximately 6 months after Dose 2 
for all participants inStage 3
Amended text so that the stopping rules apply to 
an RNA platform rather than a specific vaccine 
candidate
Original protocol 15April 2020 N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country  health authorities and IRBs/ECs.
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FDA-CBER-2021-5683-0014062
PF-07302048 (BNT162 RNA- Based COVID- 19 Vaccines)
Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 10TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ................... 15
1. PROTOCOL  SUMMARY ................................ ................................ ................................ ...17
1.1. Sy nopsis ................................ ................................ ................................ .................. 17
1.2. Schema ................................ ................................ ................................ .................... 25
1.3. Schedule of Activities ................................ ................................ ............................. 26
1.3.1. Phase 1 ................................ ................................ ................................ ........ 26
1.3.2. Phase 2/3................................ ................................ ................................ .....31
2. INTRODUCTION ................................ ................................ ................................ ............... 34
2.1. Study  Rationale ................................ ................................ ................................ .......34
2.2. Background ................................ ................................ ................................ ............. 34
2.2.1. Clinical Overview ................................ ................................ ....................... 35
2.3. Benefit/Risk Assessment................................ ................................ ......................... 35
2.3.1. Risk Assessment ................................ ................................ ......................... 37
2.3.2. Benefit Assessment ................................ ................................ ..................... 39
2.3.3. Overall Benefit/Risk Conclusion ................................ ................................ 39
3. OBJECTI VES, ESTIMANDS, AND ENDPOINTS ...........................................................39
3.1. For Phase 1 ................................ ................................ ................................ .............. 39
3.2. For Phase 2/3 ................................ ................................ ................................ ........... 41
4. STUDY DESIGN ................................ ................................ ................................ ................. 44
4.1. Overall Desig n................................ ................................ ................................ ......... 44
4.1.1. Phase 1 ................................ ................................ ................................ ........ 44
4.1.2. Phase 2/3................................ ................................ ................................ .....45
4.2. Scientific Rationale for Study  Design ................................ ................................ .....47
4.3. Justification for Dose ................................ ................................ .............................. 47
4.4. End of Study  Definition ................................ ................................ .......................... 48
5. STUDY POPUL ATION ................................ ................................ ................................ ......48
5.1. I nclusion Criteria ................................ ................................ ................................ .....48
5.2. Exclusion Criteria ................................ ................................ ................................ ....49
5.3. L ifesty le Considerations ................................ ................................ .......................... 52
5.3.1. Contraception ................................ ................................ .............................. 52
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Protocol C4591001
Protocol Amendment 9, 29 October 2020
 CONFIDENTIAL
CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 115.4. Screen Failures ................................ ................................ ................................ ........ 52
5.5. Criteria for Temporarily  Delay ing Enrollment/Randomization/Study  
Intervention Administration ................................ ................................ ...................... 52
6. STUDY INTERVENTIO N................................ ................................ ................................ ..53
6.1. Study  Intervention(s) Administered ................................ ................................ ........ 54
6.1.1. Manufacturing Process ................................ ................................ ............... 54
6.1.2. Administration ................................ ................................ ............................ 54
6.2. Prepara tion/Handling/Storage/Accountability ................................ ........................ 55
6.2.1. Preparation and Dispensing ................................ ................................ ........ 56
6.3. Measures to Minimize Bias: Randomization and Blinding ................................ .....56
6.3.1. Allocation to Study Intervention ................................ ................................ 56
6.3.2. Blinding of Site Personnel ................................ ................................ .......... 56
6.3.3. Blinding of the Sponsor................................ ................................ .............. 57
6.3.4. Breaking the Blind ................................ ................................ ...................... 58
6.4. Study  Intervention Compliance ................................ ................................ ............... 58
6.5. Concomitant Therapy ................................ ................................ .............................. 58
6.5.1. Prohibited During the Study ................................ ................................ .......58
6.5.2. Permitted During the Study ................................ ................................ ........ 59
6.6. Dose Modification ................................ ................................ ................................ ...59
6.7. I ntervention After the End of the Study ................................ ................................ ..60
7. DI SCONTINUATION O F STUDY INTERVENTION AND PARTI CIPANT 
DISCONTINUATION/WI THDRAWAL ................................ ................................ ........... 60
7.1. Discontinuation of Study  Intervention ................................ ................................ ....60
7.2. Participant Discontinuation/Withdrawal From the Study ................................ .......61
7.2.1. Withdrawal of Consent ................................ ................................ ............... 62
7.3.Lost to Follow -up ................................ ................................ ................................ ....62
8. STUDY ASSESSMENTS AND PROCEDURES ................................ ............................... 62
8.1. Efficacy  and/or Immunogenicity Assessments ................................ ....................... 63
8.1.1. Biological Samples ................................ ................................ ..................... 66
8.2. Safet y Assessments ................................ ................................ ................................ .66
8.2.1. Cli nical Safety  Laboratory  Assessments (Phase 1 Participants Onl y).......67
8.2.2. Electronic Diary ................................ ................................ .......................... 67
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 128.2.2.1. Grading Scales ................................ ................................ ........... 68
8.2.2.2. L ocal Reactions ................................ ................................ ......... 68
8.2.2.3. Systemic Events ................................ ................................ ........ 69
8.2.2.4. Fever ................................ ................................ .......................... 70
8.2.2.5. Antipy retic Medication ................................ ............................. 71
8.2.3. Phase 1 Stopping Rules ................................ ................................ .............. 71
8.2.4.Surveillance of Events That Could Represent Enhanced COVID -19 
and Phase 2/3 Stopping Rule ................................ ................................ ........... 72
8.2.5. Randomization and Vaccination After a Stopping Rule Is Met ................. 73
8.2.6. Pregnancy  Testing ................................ ................................ ...................... 73
8.3. Adverse Events and Serious Adverse Events................................ .......................... 73
8.3.1. Time Period and Frequency  for Collecting AE and SAE Information .......73
8.3.1.1. Reporting SAEs to Pfizer Safety ................................ ............... 74
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF................... 74
8.3.2. Method of Detecting AEs and SAEs ................................ .......................... 75
8.3.3. Follow -up of AEs and SAEs ................................ ................................ .......75
8.3.4. Regulatory Reporting Requirements for SAEs ................................ ........... 75
8.3.5. Exposure During Pregnancy  or Breastfeeding, and Occupational 
Exposure ................................ ................................ ................................ .......... 75
8.3.5.1. Exposure During Pregnancy ................................ ...................... 76
8.3.5.2. Exposure During Breastfeeding ................................ ................ 77
8.3.5.3. Occupational Exposure ................................ ............................. 78
8.3.6. Cardiovascular and Death Events ................................ ............................... 78
8.3.7. Disease -Related Events and/or Disease -Related Outcomes Not 
Qualifying as AEs or SAEs ................................ ................................ .............. 78
8.3.8. Adverse Events of Special Interest ................................ ............................. 79
8.3.8.1. Lack of Efficacy ................................ ................................ ........ 79
8.3.9. Medical Device Deficiencies ................................ ................................ ......79
8.3.10. Medication Errors ................................ ................................ ..................... 79
8.4. Treatment of Overdose................................ ................................ ............................ 80
8.5.Pharmacokinetics ................................ ................................ ................................ ....80
8.6. Pharmacod ynamics ................................ ................................ ................................ ..80
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 138.7. Genetics ................................ ................................ ................................ ................... 80
8.8. Biomarkers ................................ ................................ ................................ .............. 81
8.9. I mmunogenicit y Assessments ................................ ................................ ................. 81
8.10. Health Economics ................................ ................................ ................................ .81
8.11. Stud y Procedures ................................ ................................ ................................ ...81
8.11.1. Phase 1 ................................ ................................ ................................ ......81
8.11.1.1. Screening: (0 to 28 Day s Before Visit 1) ................................ 81
8.11.1.2. Visit 1 – Vaccination 1: (Day  1) ................................ ............. 82
8.11.1.3. Visit 2 – Next -Day Follow -up Visit (Vaccination 1): (1 
to 3 Day s After Visit 1) ................................ ................................ .....84
8.11.1.4. Visit 3 – 1- Week Follow -up Visit (Vaccination 1): (6 to 
8 Day s After Visit 1) ................................ ................................ ......... 86
8.11.1.5. Visit 4 – Vaccination 2: (19 to 23 Day s After Visit 1) ........... 87
8.11.1.6. Visit 5 – 1- Week Follow -up Visit (Vaccination 2): (6 to 
8 Day s After Visit 4) ................................ ................................ ......... 89
8.11.1.7. Visit 6 – 2- Week Follow -up Visit (Vaccination 2): (1 2 to 
16 Day s After Visit 4) ................................ ................................ .......90
8.11.1.8. Visit 7 – 1- Month Follow -up Visit: (28 to 35 Day s After 
Visit 4) ................................ ................................ ............................... 91
8.11.1.9. Visit 8 – 6- Month Follow -up Visit: (175 to 189 Day s 
After Visit 4) ................................ ................................ ...................... 92
8.11.1.10. Visit 9 – 12- Month Follow -up Visit: (350 to 378 Day s 
After Visit 4) ................................ ................................ ...................... 92
8.11.1.11. Visit 10 – 24- Month Follow -up Visit: (714 to 742 Day s 
After Visit 4) ................................ ................................ ...................... 93
8.11.2. Phase 2/3................................ ................................ ................................ ...93
8.11.2.1. Visit 1 – Vaccination 1: (Day  1) ................................ ............. 93
8.11.2.2. Visit 2 – Vaccination 2: (19 to 23 Day s After Visit 1) ........... 96
8.11.2.3. Visit 3 – 1- Month Follow -up Visit (After Vaccination 2): 
(28 to 35 Day s After Visit 2) ................................ ............................. 98
8.11.2.4. Visit 4 – 6- Month Follow -up Visit: (175 to 189 Day s 
After Visit 2) ................................ ................................ ...................... 99
8.11.2.5. Visit 5 – 12- Month Follow -up Visit: (350 to 378 Day s 
After Visit 2) ................................ ................................ ...................... 99
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After Visit 2) ................................ ................................ .................... 100
8.12. Unscheduled Visit for a Grade 3 or Suspected Grade 4 Reaction ...................... 100
8.13. COVID -19 Surveillance (All Participants) ................................ ......................... 101
8.13.1. Potential COVI D-19 Illness Visit: (Optimally Within 3 Day s After 
Potential COVI D-19 Illness Onset) ................................ ............................... 103
8.13.2. Potential COVI D-19 Convalescent Visit: (28 to 35 Day s After 
Potential  COVI D-19 Illness Visit) ................................ ................................ 104
8.14. Communication and Use of Technology ................................ ............................. 105
8.15. SARS -CoV -2 NAAT Results From Visits 1 and 2 and Potential COVID -19 
Illness Visits ................................ ................................ ................................ ............ 105
9. STATI STICAL CONSI DERATIONS ................................ ................................ .............. 106
9.1. Estimands and Statistical Hy potheses ................................ ................................ ...106
9.1.1. Estimands ................................ ................................ ................................ ..106
9.1.2. Statistical Hypotheses ................................ ................................ ............... 107
9.1.2.1. Statistical Hy pothesis Evaluation for Efficacy ........................ 107
9.1.2.2. Statistical Hy pothesis Evaluation for Immunogenicity ........... 107
9.2. Sample Size Determination ................................ ................................ ................... 107
9.3. Analy sis Sets ................................ ................................ ................................ ......... 109
9.4. Statistical Analy ses................................ ................................ ............................... 110
9.4.1. I mmunogenicit y Analyses ................................ ................................ ........ 110
9.4.2. Efficacy  Anal yses................................ ................................ ..................... 115
9.4.3. Safet y Anal yses................................ ................................ ........................ 117
9.4.4. Other Anal yses................................ ................................ .......................... 118
9.5. I nterim Anal yses................................ ................................ ................................ ...119
9.5.1. Ana lysis Timing ................................ ................................ ........................ 122
9.6. Data Monitoring Committee or Other Independent Oversight Committee ........... 122
10. SUPPORTING DOCUM ENTATION AND OPERATI ONAL 
CONSI DERATIONS ................................ ................................ ................................ ........ 124
10.1. Appendix 1: Regulatory , Ethical, and Study  Oversight Considerations ............. 124
10.1.1. Regulatory and Ethical Considerations ................................ .................. 124
10.1.1.1. Reporting of Safety  Issues and Serious Breaches of the 
Protocol or I CH GCP ................................ ................................ .......124
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Page 1510.1.2. I nformed Consent Process ................................ ................................ ......125
10.1.3. Data Protection ................................ ................................ ....................... 126
10.1.4. Dissemination of Cli nical Study  Data ................................ .................... 126
10.1.5. Data Qualit y Assurance ................................ ................................ .......... 127
10.1.6. Source Documents ................................ ................................ .................. 129
10.1.7. Study  and Site Start and Closure ................................ ............................ 129
10.1.8. Sponsor’s Qualified Medical Personnel ................................ ................. 130
10.2. Appendix 2: Clinical Laboratory  Tests ................................ ............................... 131
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow -up, and Reporting ................................ ................................ ....133
10.3.1. Definition of AE ................................ ................................ ..................... 133
10.3.2. Definition of SAE ................................ ................................ ................... 134
10.3.3. Recording/Reporting and Follow- up of AEs and/or SAEs ..................... 136
10.3.4. Reporting of SAEs................................ ................................ .................. 139
10.4. Appendix 4: Contraceptive Guidance ................................ ................................ .140
10.4.1. Male Participant Reproductive Inclusion Criteria ................................ ..140
10.4.2. Female Participant Reproductive Inclusion Criteria ............................... 140
10.4.3. Woman of Childbearing Potential ................................ .......................... 141
10.4.4. Contraception Methods ................................ ................................ ........... 142
10.5. Appendix 5: L iver Safety : Suggested Actions and Follow -up Assessments ......144
10.6. Appendix 6: Abbreviations ................................ ................................ ................. 146
10.7. Appendix 7: Stopping and Alert Rules for Enhanced COVID -19 ...................... 150
10.8. Appendix 8: Criteria for Allowing Inclusion of Participants With Chronic 
Stable HIV, HCV, or HBV Infection ................................ ................................ ......153
11. REFERENCES ................................ ................................ ................................ ................ 154
LIST OF TABLES
Table 1. Local Reaction Grading Scale ................................ ................................ ..69
Table 2. Systemic Event Grading Scale ................................ ................................ ..69
Table 3. Scale for Fever ................................ ................................ .......................... 70
Table4. Power Anal ysis for Noninferiorit y Assessment ................................ .....108
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Rates With Different Sample Sizes ................................ ........................ 109
Table 6. Interim Anal ysis Plan and Boundaries for Efficacy  and Futility ............ 120
Table 7. Statistical Design Operating Characteristics: Probability  of Success 
or Failure for Interim Analy ses................................ ............................... 121
Table 8. Statistical Design Operating Characteristics: Probability  of Success 
for Final Anal ysis and Overall ................................ ................................ 121
Table 9. Laboratory  Abnormality  Grading Scale ................................ ................. 131
Table 10. Stopping Rule: Enrollment I s Stopped if the Number of Severe 
Cases in the Vaccine Group I s Greater Than or Equal to the 
Prespecified Stopping Rule Value (S) ................................ .................... 151
Table 11. Alert Rule: Further Action I s Taken if the Number of Severe Cases 
in the Vaccine Group Is Greater Than or Equal to the Prespecified 
Alert Rule Value (A) ................................ ................................ .............. 152
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Page 171.PROTOCOL SUMMARY
1.1.Synopsis
Short Title: A Phase 1/2 /3Study  to Evaluate the Safety , Tolerabilit y, Immunogenicity, and 
Efficacy  of RNA Vaccine Candidates Against COVID -19 in Healthy  Individuals
Rationale
A pneumonia of unknown cause detected in Wuhan, China, was first reported in 
December 2019. On 08 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 officiall y 
named as s evere acute respiratory  syndrome corona virus 2 (SARS -CoV -2), and the WHO 
officiall y named the disease caused by SARS -CoV -2 as coronavirus disease 2019 
(COVID -19). On11 March 2020 , the WHO upgraded the status of the COVID- 19 outbreak 
from epidemic to pandemic , which is now spreading globall y at high speed.
There are currently  no licensed vaccines to prevent infection with SARS -CoV -2or 
COVID -19. Given the rapid transmission of COV ID-19 and incidence of disease in the 
United States and elsewhere, the rapid development of an effective vaccine is of utmost 
importance.
BioNTech has developed RNA -based vaccine candidates using a platform approach that 
enable s the rapid development of vaccines against emerging viral diseases, including 
SARS -CoV -2.Each vaccine candidate is based on aplatform ofnucleoside -modified 
messenger RNA (modRNA , BNT162b ). Each vaccine candidate expresses 1 of 2 antigen s: 
the SARS -CoV -2 full-length, P2 mutant , prefusion spike gl ycoprotein (P2 S ) (version 9) or a 
trimerized SARS -CoV -2 spike gl ycoprotein receptor -binding domain (RBD ) (version 5). 
The 2 SARS -CoV -2 vaccine candidates that will be tested in this study aretherefore :
BNT162b1 (variant RBP020.3) : a modRNA encoding the RBD ;
BNT162b 2 (variant RBP020.2) :a modRNA encoding P2 S.
All candidates are formulated in the same lipid nanoparticle (LNP) composition . This study  
is intended to investigate the safet y, immunogenicity , and efficacy  of these prophy lactic 
BNT162 vaccines against COVI D-19 .
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Page 18Objectives , Estimands, and Endpoints
For Phase 1
Objectives Estimands Endpoints
Primary: Primary: Primary: 
To describe the safety and tolerability 
profiles of prophylactic BNT162 
vaccines in healthy adults after 1or 2 
dosesIn participants receiving at least 1 dose 
of study intervention, 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
 Adverse events (AE s) from 
Dose 1 to1 month after the last 
dose
 Serious AEs (SAE s) from Dose 1 
to 6 months after the last dose Local reactions (pain at the 
injection site , rednes s, and 
swelling )
 Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened muscle 
pain, and new or worsened joint 
pain)
 AEs
 SAEs
In addition, the percentage of 
participants with :
 Abnormal hematology and 
chemistry laboratory v alues 1 and 
7 days after Dose 1; and 7 days 
after Dose 2
 Grading shifts in hematology and 
chemistry laboratory assessments 
between baseline and 1 and 7 days 
after Dose 1; and before Dose 2 
and 7 days after Dose 2Hematology and chemistry laboratory 
parameters detailed in Section 10.2
Secondary: Secondary: Secondary: 
To describe the immune responses 
elicited by prophylactic BNT162 
vaccines in healthy adults after 1or 2 
dosesIn participants complying with the key 
protocol criteria (evaluable 
participants) at the following time 
points after receipt of study 
intervention :
7 and 21 days after Dose 1; 7 and 14
days and 1, 6, 12, and 24 months after 
Dose 2
 Geometric mean titers (GMTs) at 
each time point
 Geometric mean fold rise (GMFR) 
from before vaccination to each 
subsequent time point after 
vaccination
 Proportion of participants 
achieving ≥4-fold rise from before 
vaccination to each subsequent 
time point after vaccinationSARS -CoV -2neutralizing titers
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 Geometric mean concentrations 
(GMCs) at each time point
 GMFR from before vaccination to 
each subsequent time point after 
vaccination
 Proportion of participants 
achieving ≥4-fold rise from before 
vaccination to each subsequent 
time point after vaccinationS1-binding IgGlevels and 
RBD -binding IgG levels
 Geometric mean ratio (GMR) , 
estimated by the ratio of the 
geometric mean of SARS -CoV -2
neutralizing titers to the geometric 
mean of binding IgGlevels at each 
time point SARS -CoV -2neutralizing titers
 S1-binding IgGlevels
 RBD -binding IgGlevels
For Phase 2/3
ObjectivesaEstimands Endpoints
Prim ary Efficacy
To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19occurrin g from 
7 days after the second dose in 
participants without evidence of 
infection before vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) at least 7 days after 
receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT in participants with 
no serological or virological evidence 
(up to 7 days after receipt of the 
second dose) of past SARS -CoV -2 
infection
To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19 occurring from 
7 days after the second dose in 
participants with and without 
evidence of infection before 
vaccinationIn participants co mplying with the 
key protocol criteria (evaluable 
participants) at least 7 days after 
receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT
Prim ary Safety
To define the safety profile of 
prophylactic BNT162 b2in the first 
360 participants randomized (Phase 2)In participants receiving at least 1 
dose of study intervention, 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 from Dose 1 to 7 days after 
the second dose
 SAEs from Dose 1 to 7 days
after the second dose Local reactions (pain at the 
injection site, redness, and 
swelling)
 Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened 
muscle pain, and new or 
worsened joint pain)
 AEs
 SAEs
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To define the safety profile of 
prophylactic BNT162 b2in all 
participants randomized in Phase 2/3In participants receiving at least 
1 dose of study intervention, 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 from Dose 1 to 1 month 
after the second dose
 SAEs from Dose 1 to 6 months 
after the second dose AEs
 SAEs
 In a subset of at least 6000 
participants:
o Local reactions (pain at the 
injection site, redness, and 
swelling)
o Systemic events (fever, 
fatigue, headache, chills, 
vomiting, diarrhea, new or 
worsened muscle pain, and 
new or worsened joint pain )
To define the safety profile of 
prophylactic BNT162 b2in 
participants 12 to 15 years of age in 
Phase 3In participants receiving at least 
1 dose of study intervention, 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 from Dose 1 to 1 month 
after the second dose
 SAEs from Dose 1 to 6 months 
after the second dose Local reacti ons (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 Efficacy
To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19 occurring from 
14days after the second dose in 
participants without evidence of 
infection before vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) at least 14days after 
receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT in participants with 
no serologic al or virological evidence 
(up to 14days after receipt of the 
second dose) of past SARS -CoV -2 
infection
To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19 occurring from 
14days after the second dose in 
participants with and without 
evidence of infection before 
vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) at least 14days after 
receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT
To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed severe COVID -19
occurring from 7days and from 
14days after the second dose in 
participants without evidence of 
infection before vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of 
study intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]Confirmed s evere COVID -19 
incidence per 1000 person -years of 
follow -up in participants with no 
serological or virological evidence (up 
to 7 days and up to 14 days after 
receipt of the secon d dose) of past 
SARS -CoV -2 infection
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To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed severe COVID -19
occurring from 7 days and from 
14days after the second dose in 
participants with and without 
evidence of infection before 
vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of 
study intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]Confirmed severe COVID -19
incidence per 1000 person -years of 
follow -up
To describe the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19 (according to 
the CDC -defined symptoms) 
occurring from 7 days and from 
14days after the second dose in 
participants without evidence of 
infection before vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of 
study intervention:
100 × (1 –IRR) [ratio of active 
vacci ne to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT in participants with
no serological or virological evidence 
(up to 7days and up to 14 days after 
receipt of the second dose) of past
SARS -CoV -2 infection
To describe the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19 (according to 
the CDC -defined symptoms) 
occurring from 7 days and from 
14days after the second dose in 
participants with and without 
evidence of infection before 
vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of 
study intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT
Secondary Immunogenicity
Todemonstrate the noninferiority of 
the immune response to prophylactic 
BNT162b2 in participants 12 to 15 
years of age compared to participants 
16 to 25 years of ageGMR, estimated by the ratio of the 
geometric mean of SARS -CoV -2 
neutralizing titers in the 2 age groups 
(12-15 years of age to 16 -25 years of 
age) 1 month after completion of 
vaccinationSARS -CoV -2 neutralizin g titers in 
participants with no serological or 
virological evidence (up to 1 month
after receipt of the second dose) of 
past SARS -CoV -2 infection
Exploratory
To evaluate the immune response 
over time to prophylactic BNT162 b2
and persistence of immune response 
in participants with and without 
serological or virological evidence of 
SARS -CoV -2infection before 
vaccinationGMC/ GMT, GMFR, and percentage 
of participants with titers greater than  
defined threshold(s), at baseline and 
1, 6, 12, and 24 months after 
completion of vaccination S1-binding IgGlevels and/or 
RBD -binding IgGlevels
 SARS -CoV -2 neutralizing titers
To evaluate the immune response
(non-S) to SARS -CoV -2 in 
participants with and without 
confirmed COVID -19 during the 
study N-binding antibody
To describe the serological responses 
to the BNT vaccine candidate in cases 
of:
 Confirmed COVID-19
 Confirmed severe COVID -19
 SARS -CoV -2 infection without 
confirmed COVID -19 S1-binding IgGlevels and/or 
RBD -binding IgGlevel s
 SARS -CoV -2 neutralizing titers
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To describe the safety, 
immunogenicity ,and efficacy of 
prophylactic BNT162b2 in 
individuals with confirmed stable HIV 
disease All safety, immunogenicity, and 
efficacy endpoints described 
above
To describe the safety and
immunogenicity of prophylactic 
BNT162b2 in individuals 16 to 55 
years of age vaccinated with study 
intervention produced by 
manufacturing “Process 1” or 
“Process 2”b All safety endpoints described 
above
 SARS -CoV -2 neutralizing titers
a.HIV-positive participants in Phase 3 will not be included in analyses of the objectives, with the 
exception of the specific exploratory objective.
b.See Section 6.1.1 for a description of the manufacturing process.
Overall Design
This is a Phase 1/2 /3, multicenter, multinational, randomized, placebo -controlled, 
observer -blind, dose -finding, vaccine candidate– selection ,and efficacy study  in healthy  
individuals.
The study  consists of 2 parts :Phase 1: to identify  preferred vaccine candidate(s) and dose 
level(s); Phase 2/3: an expan ded cohort and efficacy part.  These parts, and the progression 
between them, are detailed in the schema ( Section 1.2).
The study  will evaluate the safet y, tolerability , and immunogenicit yof 2different 
SARS -CoV-2 R NAvaccine candidate s against C OVID -19and the efficacy  of 1 candidate :
As a 2 -dose (separated by  21 day s) schedule ;
At various different dose levels in Phase 1;
In 3 age groups ( Phase 1: 18 to 55 y ears of age, 65 to 85 y ears of age ; Phase 2/3: ≥12 
years of age [stratified as 12-15, 16 -55,or >55years of age] ).
Dependent upon safet y and/or immunogenicit y data generated during the course of this 
study , or the BioNTech study  conducted in Germany  (BNT162 -01), it is possible that groups 
in Phase 1 may  be started at the next highest dose, g roups may  not be started, groups may  be 
terminated early , and /orgroups may  be added with dose levels below the lowest stat ed dose 
or intermediate between the lowest and highest stated doses.
The vaccine candidate selected for Phase 2/3 evaluation is BNT162b 2at a dose of 30µg.
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Each group in Phase 1 will comprise 15 participants (12 receiving active vac cine and 
3receiving placebo). In this phase , 13groups will be studied, correspond ingto a total of 
195participants.
The vaccine candidate selected for Phase 2/ 3, BNT162b 2at a dose of 30 µg,will comprise 
21,999 vaccine recipients .The 12- to 15 -year stratum will comprise up to approximately
2000 participants ( 1000 vaccine recipients) enrolled at selected investigational sites. It is 
intended that a minimum of 40% of participants will be in the >55-year stratum. An equal 
number of participants will r eceive placebo, ie, randomized in a 1:1 ratio.
Intervention Groups and Duration
The study  will evaluate a 2-dose (separated b y 21 days) schedule of various different dose 
levels of 2 investigational RNA vaccine candidate s for active immunization against 
COVID -19in 3 age groups ( Phase 1: 18 to 55 years of age ,65 to 85 y ears of age ; Phase 2/3:
≥12years of age [stratified as 12-15, 16 -55,or >55 years of age] ):
BNT162b1 (BNT162 RNA -LNP vaccine utilizing modRNA and encoding the RBD ): 
10µg, 20µg,30µg, 100 µg
BNT162b2 (BNT162 RNA -LNP vaccine utilizing modRNA and encoding the P2 S ): 
10µg, 20µg,30µg
The vaccine candidate selected for Phase 2/3 evaluation is BNT162b 2at a dose of 30µg.
Participants are expected to participate for up to a maximum of app roximately 26 months. 
The duration of stud y follow -up may  be shorter among participants enrolled in Phase 1 
dosing arms that are not evaluated in Phase 2/ 3.
Data Monitoring Committee or Other Independent Oversight Committee
The study  will utilize an IRC, an internal Pfizer committee thatwill review data to allow 
dose escalation or changes to continuation of specific groups . 
An external data monitoring committee (DMC) will be formed and will review cumulative 
unblinded data throughout the study .
Statistic al Methods
Thesample size for Phase 1 of the stud y is not based on an y statistical h ypothesis testing.
For Phase 2/3, the VE evaluation will be the primary  objective . The VE is defined as 
VE= 100 × (1–IRR), where IRR is calculated as the ratio of the first confirmed COVID -19 
illness rate in the vaccine group to the corresponding illness rate in the placebo group. With 
assumptions of a true VE of 60%and 4 IAs planned , 164 COVID -19cases will provide 90% 
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Page 24power to conclude true VE > 30%. This would be a chieved with a total 43,998 participants 
(21,999 vaccine recipients ), based on the assumption of a 1.3 % per y earincidence in the 
placebo group, accrual of 164 primary -endpoint cases within 6 months, and 20% of the 
participants being nonevaluable.   If the attack rate is much higher, case accrual would be 
expected to be more rapid, enabling the study ’s primary  endpoint to be evaluated much 
sooner .The total number of participants enrolled in Phase 2/3 may  vary  depending on the 
incidence of COVID -19 at the time of the enrollment, the true underly ing VE, and a potential 
early stop for efficacy or futility.
VE will be evaluated using a beta-binomial model and the posterior probability  of VE being 
>30% will be assessed.
In Phase 3, up to approximately 2000 part icipants are anticipated to be 12 to 15 y ears of age. 
Noninferiorit y of immune response to proph ylactic BNT162b2 in participants 12 to 15 years 
of age to response in participants 16 to 25years of age will be assessed based on the GM Rof 
SARS -CoV -2 neutralizing titers using a 1.5 -fold margin. A sample size of 200 evaluable 
participants (or 250vaccine recipients) per age group will provide a power of 90.8% to 
declare the noninferiority in terms of GM R(lower limit of 95% CI for GMR>0.67).
The primary  safet y objective will be evaluated b y descriptive summary  statistics for local 
reactions, s ystemic events ,AEs/SAEs ,and abnormal hematology  and chemistry  laboratory  
parameters (Phase 1 only), for each vacci ne group. A 3-tier approach will be used to 
summarize AEs in Phase 2/3.
Except for the objective to assess the noninferiority  of immune response in participants 12 to 
15 years of age compared to participants 16 to 25 years of age, the other immunogenicit y 
objectives will be evaluated d escriptivel y by GMT, GMC, GMFR, percentage of participants 
with ≥4-fold rise, percentage of participants with ≥specified threshold ,and GMC ratio, and 
the associated 95% confidence interval s(CIs), for SARS -CoV -2neutralizing titers, 
S1-binding IgGlevels ,and/orRBD- binding IgGlevels at the various time points.
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Page 251.2.Schema
Phase 1 For each vaccine candidate (4:1 randomization active:placebo)
Age: 18-55 y Age: 65-85 y
Low-dose -level 2 -dose group (n=15)
IRC (safety) IRC (safety Low-dose -level 2 -dose group (n=15)
after Dose 1)
Mid-dose -level 2 -dose group (n=15)
IRC (safety) IRC (safety Mid-dose -level 2 -dose group (n=15)
after Dose 1)
High -dose -level 2 -dose group (n=15)
IRC (safety High -dose -level 2 -dose group (n=15)
after Dose 1)
IRC choice of group(s) for Phase 2/3
(safety & immunogenicity after Dose s1 and 2)
Phase 2/ 3 Single vaccine candidate (1:1 randomization active:placebo)
Safety and immunogenicity analysis of 
Phase 2 data (first 360 participants) 
by unblinded team (these participants
will also be included in Phase 3 
analyses)Age: ≥12
(Stratified 12-15, 16-55 ,or >55)
BNT162b 230µgor placebo 2doses
(n~21,999 per group , total n~ 43.998 )
Abbreviation: IRC = internal review committee.
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Page 261.3. S chedule of Activ ities
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  sche dule visits (unplanned visits) in additi on to those listed in the SoA table , in order to conduct evaluations or 
assessments required to protect the well -being of the participant .
1.3.1. Phase 1 
Anunplanned potential COVID-19 illness visit and unplanned potential COVID- 19 convalescent visit are requi red at an y time 
between Visit 1 (Vaccination 1) and Visit 10 (24 -month follow -up visit) that COVID -19 is suspected.
Visit Number Screening 1 2 3 4 5 6 7 8 9 10 Unplanned Unplanned
Visit Description Screening Vax 1 Next -
Day 
Follow -
up Visit 
(Vax 1) 1-Week
Follow -
up Visit 
(Vax 1)Vax 2 1-Week
Follow -
up Visit 
(Vax 2)2-Week
Follow -
up Visit 
(Vax 2) 1-Month 
Follow -
up Visit6-Month
Follow -
up Visit12-
Month 
Follow -
up Visit24-
Month 
Follow -
up VisitPotential 
COVID -19 
Illness 
VisitaPotential 
COVID -19 
Convalescent 
Visit
Visit Window (Days) 0 to 28
Days 
Before 
Visit 1Day 1 1 to 3 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 119 to 23 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 412to 16 
Days 
After 
Visit 428 to 35 
Days 
After 
Visit 4175to 
189Days 
After 
Visit 4350 to 
378 Days 
After 
Visit 4714 to 
742 Days 
After 
Visit 4Optimally 
Within 3 
Days After 
Potential 
COVID -19 
Illness 
Onset28 to 35 Days 
After 
Potential 
COVID -19 
Illness Visit
Obtain informed consent X
Assign participant number X
Obtain demography and 
medical history dataX
Obtain details of medications 
currently takenX
Perform physical examination X X X X X X X
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Page 27Visit Number Screening 1 2 3 4 5 6 7 8 9 10 Unplanned Unplanned
Visit Description Screening Vax 1 Next -
Day 
Follow -
up Visit 
(Vax 1) 1-Week
Follow -
up Visit 
(Vax 1)Vax 2 1-Week
Follow -
up Visit 
(Vax 2)2-Week
Follow -
up Visit 
(Vax 2) 1-Month 
Follow -
up Visit6-Month
Follow -
up Visit12-
Month 
Follow -
up Visit24-
Month 
Follow -
up VisitPotential 
COVID -19 
Illness 
VisitaPotential 
COVID -19 
Convalescent 
Visit
Visit Window (Days) 0 to 28
Days 
Before 
Visit 1Day 1 1 to 3 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 119 to 23 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 412to 16 
Days 
After 
Visit 428 to 35 
Days 
After 
Visit 4175to 
189Days 
After 
Visit 4350 to 
378 Days 
After 
Visit 4714 to 
742 Days 
After 
Visit 4Optimally 
Within 3 
Days After 
Potential 
COVID -19 
Illness 
Onset28 to 35 Days 
After 
Potential 
COVID -19 
Illness Visit
Measure vital signs
(including body temperature)X X X X X X X
Collect blood sample for 
hematology and chemistry 
laboratory testsb~10 mL ~10 mL ~10 mL ~10 mL ~10 mL
Collect screening blood 
sample for HIV, HBsAg, 
HBc Ab, and HCV Ab tests~10 mL
Serological testfor prior 
COVID -19 infection~20 mL
Perform urine pregnancy test 
(if appropriate)X X X
Obtain nasal (midturbinate) 
swab(s)cX X X
Collect nonstudy vaccine 
information X X X X X X X X X
Confirm eligibility X X X
Collect prohibited medication 
useX X X X X X X X X X X
Review hematology and 
chemistry resultsX X X X X
Review temporary delay 
criteriaX X
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Page 28Visit Number Screening 1 2 3 4 5 6 7 8 9 10 Unplanned Unplanned
Visit Description Screening Vax 1 Next -
Day 
Follow -
up Visit 
(Vax 1) 1-Week
Follow -
up Visit 
(Vax 1)Vax 2 1-Week
Follow -
up Visit 
(Vax 2)2-Week
Follow -
up Visit 
(Vax 2) 1-Month 
Follow -
up Visit6-Month
Follow -
up Visit12-
Month 
Follow -
up Visit24-
Month 
Follow -
up VisitPotential 
COVID -19 
Illness 
VisitaPotential 
COVID -19 
Convalescent 
Visit
Visit Window (Days) 0 to 28
Days 
Before 
Visit 1Day 1 1 to 3 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 119 to 23 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 412to 16 
Days 
After 
Visit 428 to 35 
Days 
After 
Visit 4175to 
189Days 
After 
Visit 4350 to 
378 Days 
After 
Visit 4714 to 
742 Days 
After 
Visit 4Optimally 
Within 3 
Days After 
Potential 
COVID -19 
Illness 
Onset28 to 35 Days 
After 
Potential 
COVID -19 
Illness Visit
Confirm use of contraceptives 
(ifappropriate)X X X X X X X X
Obtain randomization number
and study intervention 
allocationX
Collect blood sample for 
immunogenicity assessment ~50 mL ~50 mL ~50 mL ~50 mL
+ 
optionale
~170 mL~50 mL
+ 
optionale
~170 mL~50 mL
+ 
optionale
~170 mL~20 mL ~20 mL ~20 mL ~20 mL
Administer study intervention X X
Assess acute reactions for at 
least 30 minutes after study 
intervention administrationdX X
Explain participant
communication methods 
(including for e -diary 
completion), assist the 
participant with downloading 
the app, or issue provisioned 
device, if requiredX
Provide thermometer and 
measuring deviceX X
Review reactogenicity e-diary 
data (daily review is optimal 
during the active diary period)
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Page 29Visit Number Screening 1 2 3 4 5 6 7 8 9 10 Unplanned Unplanned
Visit Description Screening Vax 1 Next -
Day 
Follow -
up Visit 
(Vax 1) 1-Week
Follow -
up Visit 
(Vax 1)Vax 2 1-Week
Follow -
up Visit 
(Vax 2)2-Week
Follow -
up Visit 
(Vax 2) 1-Month 
Follow -
up Visit6-Month
Follow -
up Visit12-
Month 
Follow -
up Visit24-
Month 
Follow -
up VisitPotential 
COVID -19 
Illness 
VisitaPotential 
COVID -19 
Convalescent 
Visit
Visit Window (Days) 0 to 28
Days 
Before 
Visit 1Day 1 1 to 3 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 119 to 23 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 412to 16 
Days 
After 
Visit 428 to 35 
Days 
After 
Visit 4175to 
189Days 
After 
Visit 4350 to 
378 Days 
After 
Visit 4714 to 
742 Days 
After 
Visit 4Optimally 
Within 3 
Days After 
Potential 
COVID -19 
Illness 
Onset28 to 35 Days 
After 
Potential 
COVID -19 
Illness Visit
Review ongoing 
reactogenicity e-diary 
symptom s and obtain stop 
datesX X
Collect AEs and SAEs as 
appropriateX X X X X X X X X X X X X
Collect e -diary or assist the 
participant to delete 
applicationX
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Page 30Visit Number Screening 1 2 3 4 5 6 7 8 9 10 Unplanned Unplanned
Visit Description Screening Vax 1 Next -
Day 
Follow -
up Visit 
(Vax 1) 1-Week
Follow -
up Visit 
(Vax 1)Vax 2 1-Week
Follow -
up Visit 
(Vax 2)2-Week
Follow -
up Visit 
(Vax 2) 1-Month 
Follow -
up Visit6-Month
Follow -
up Visit12-
Month 
Follow -
up Visit24-
Month 
Follow -
up VisitPotential 
COVID -19 
Illness 
VisitaPotential 
COVID -19 
Convalescent 
Visit
Visit Window (Days) 0 to 28
Days 
Before 
Visit 1Day 1 1 to 3 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 119 to 23 
Days 
After 
Visit 16 to 8 
Days 
After 
Visit 412to 16 
Days 
After 
Visit 428 to 35 
Days 
After 
Visit 4175to 
189Days 
After 
Visit 4350 to 
378 Days 
After 
Visit 4714 to 
742 Days 
After 
Visit 4Optimally 
Within 3 
Days After 
Potential 
COVID -19 
Illness 
Onset28 to 35 Days 
After 
Potential 
COVID -19 
Illness Visit
Collection of 
COVID -19–related clinical 
and laboratory information 
(including local diagnosis)X X
Abbreviations: e -diary = electronic diary; HBc Ab = hepatitis B core antibody; HBsAg = hepatitis B surface antigen; HCV Ab = hepatitis C virus antibody; 
HIV = human immunodeficiency virus; NAAT = nucleic acid amplification test; vax = vaccination.
a. The COVID- 19 illness visit may be conducted as an in -person or telehealth visit.
b.Hem atology: hemoglobin, complete blood count with differential, and platelets.  Blood chemistry: alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase, total bilirubin, blood urea nitrogen (BUN), and creatinine.
c.Two swabs will be taken at Visits 1 and 4. One will be tested (if possible at the site, otherwise at the central laboratory) within 24 hours and vaccination w ill 
only proceed if it i s NAAT -negative for SARS -CoV -2 genomes. The second will be sent to the central laboratory for potential later testing.
d.The first 5 participants in in each group will be observed at the site for at least 4 hours after study intervention administration. Further vaccination will 
commence no sooner than 24 hours after the fifth participant received his or her vaccination.
e.An optional blood draw  of ~1 70mL will be taken at 1 of the visits (from selected participants who consent) for exploratory COVID -19 research .
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Page 311.3.2. Phase 2/ 3
An unplanned potential COVID-19 illness visit and unplanned potential COVID- 19 convalescent visit are required at any  time 
between Visit 1 (Vaccination 1) and Visit 6(24-month follow -up visit) that potential COVID -19symptoms are reported, including 
MIS-C.
Visit Number 1 2 3 4 5 6 Unplanned Unplanned
Visit Description Vaccination 1 Vaccination 2 1-Month
Follow -up 
Visit6-Month
Follow -up 
Visit12-Month 
Follow -up 
Visit24-Month 
Follow -up 
VisitPotential 
COVID -19 
Illness VisitaPotential 
COVID -19 
Convalescent 
Visit
Visit Window (Days) Day 1b 19 to 23 Days 
After Visit 128 to 35 Days 
After Visit 2175to 189
Days After 
Visit 2350 to 378 
Days After 
Visit 2714 to 742 
Days After 
Visit 2Optimally 
Within 3 
Days After 
Potential 
COVID -19 
Illness Onset28 to 35 Days 
After 
Potential 
COVID -19 
Illness Visit
Obtain informed consent X
Assign participant number X
Obtain demography and medical history data X
Perform clinical assessmentc X
For participants who are HIV-positive , record latest 
CD4 count and HIV viral loadX X X X 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 X
Collect prohibited medication use X X X X X X X
Confirm eligibility X X
Review temporary delay criteria X X
Collect blood sample for immunogenicity 
assessmentd~20mL/
~10mL~20mL/
~10mL~20mL/
~10mL~20mL/
~10mL~20mL/
~10mL~20mL/
~10mL
Obtain  nasal (midturbinate) swab X X X
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Page 32Visit Number 1 2 3 4 5 6 Unplanned Unplanned
Visit Description Vaccination 1 Vaccination 2 1-Month
Follow -up 
Visit6-Month
Follow -up 
Visit12-Month 
Follow -up 
Visit24-Month 
Follow -up 
VisitPotential 
COVID -19 
Illness VisitaPotential 
COVID -19 
Convalescent 
Visit
Visit Window (Days) Day 1b 19 to 23 Days 
After Visit 128 to 35 Days 
After Visit 2175to 189
Days After 
Visit 2350 to 378 
Days After 
Visit 2714 to 742 
Days After 
Visit 2Optimally 
Within 3 
Days After 
Potential 
COVID -19 
Illness Onset28 to 35 Days 
After 
Potential 
COVID -19 
Illness Visit
Obtain randomization number and study 
intervention allocationX
Administer study intervention X X
Assess acute reactions for at least 30 minutes after 
study intervention administrationX X
Explain p articipant communication methods 
(including for e -diary completion), assist the 
participant with downloading the app, or issue 
provisioned device, if requiredX
Provide /ensure the participant has a thermometer
(all participants) and measuring device
(reactog enicity subset participants only)X X
Review reactogenicity e -diary data (daily review is 
optimal during the active diary period)e
Review ongoing reactogenicity e -diary symptoms 
and obtain stop dateseX X
Collect AEs and SAEs as appropriate X X X XfXfXf X Xf
Collect e -diary or assist the participant to delete 
applicationX
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Page 33Visit Number 1 2 3 4 5 6 Unplanned Unplanned
Visit Description Vaccination 1 Vaccination 2 1-Month
Follow -up 
Visit6-Month
Follow -up 
Visit12-Month 
Follow -up 
Visit24-Month 
Follow -up 
VisitPotential 
COVID -19 
Illness VisitaPotential 
COVID -19 
Convalescent 
Visit
Visit Window (Days) Day 1b 19 to 23 Days 
After Visit 128 to 35 Days 
After Visit 2175to 189
Days After 
Visit 2350 to 378 
Days After 
Visit 2714 to 742 
Days After 
Visit 2Optimally 
Within 3 
Days After 
Potential 
COVID -19 
Illness Onset28 to 35 Days 
After 
Potential 
COVID -19 
Illness Visit
Collection of COVID -19–related clinical and 
laboratory information (including local diagnosis)X X
Abbreviation s: HIV = human immunodeficiency virus; e-diary = electronic diary.
a.The COVID- 19 illness visit may be conducted as an in -person or telehealth visit.
b.The visit may be conducted across 2 consecutive days; if so, all steps from assessing the inclusion and exclusion criteria onwards must be conducted on the 
same day.
c.Including, if indicated, a physical examination.
d.20mL is to be collected from participants ≥16 years of age; 10 mL is to be collected from participants 12 to 15 years of age.
e.Reactogenicity subset participants only.
f.Any AEs occurring up to 48 hours after the blood draw  must be recorded (see Section 8.3.1 ).
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Page 342.INTRODUCTION
The BNT162 RNA -based COVID -19 vaccine sare currently  being investigated for 
prevention of COVID -19 in healthy  individuals.
2.1.Study Rationale
The purpose of the study  is to rapidly  describe the safet y, tolerabilit y, and immunogenicit y of 
2 BNT162 RNA -based COVID -19 vaccine candidates against COVID-19 , and the efficacy  
of 1 candidate, in healthy individuals. There are currentl y no licensed vaccines to prevent 
infection with SARS -CoV -2or COVID -19. Given the g lobal crisis of COVID -19 and fast 
expansion of the disease in the United States and elsewhere, the rapid development of an 
effective vaccine is of utmost importance.
2.2.Background
In Decem ber 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China.  
InJanuary  2020, it became clear that a novel coronavirus (2019 -nCoV) was the underl ying 
cause.  Later in January , the genetic sequence of the 2019 -nCoV became available to the 
Worl d Health Organization (WHO) and public (MN908947.3), and the virus was categorized 
in the Betacoronavirus subfamily .  By  sequence analy sis, the phy logenetic tree revealed a 
closer relationship to severe acute respiratory  syndrome (SARS) virus isolates than to another 
coronavirus infecting humans, the Middle East respiratory  syndrome (MERS) virus.
SARS -CoV -2 infections and the resulting disease, COVID -19,have spread globall y, 
affecting a growing number of countries.
On 11 March 2020 , the WHO characterized t he COVID -19 outbreak as a pandemic.1  
TheWHO Situation Update Report dated 30March 2020 noted 693,224 confirmed cases 
with 33,106 deaths globally , including 142,081 confirmed cases with 2457 deaths in the 
Americas .2  The United States currently  has the most re ported cases globall y. At the time of 
this communication, the number of confirmed cases continues to rise globally . There are 
currentl y no vaccines or effective antiviral drugs to treat SARS -CoV -2 infections or the 
disease it causes, COVID -19.3
A proph ylactic, RNA -based SARS -CoV -2 vaccine provides one of the most flexible and 
fastest approaches available to immunize against the emerging virus.4,5
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 eas y and rapid production and the prospect of 
producing high numbers of vaccination doses within a shorter time period than achieved with 
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Page 35traditional vaccine approaches.  This capability  is pivotal to enable the most effective 
response in outbreak scenarios.
Two SARS -CoV -2–RNA lipid nanoparticle (RNA- LNP ) vaccines based on aplatform of
nucleoside -modified messenger RNA (modRNA , BNT162b )will be evaluated in this study . 
Each vaccine candidate expresses 1 of 2 antigens: the SARS -CoV -2 full -length, P2 mutant, 
prefusion spike gl ycoprotein (P2 S) (version 9) or a trimerized SARS -CoV -2 spike 
glycoprotein-receptor binding domain (RBD) (version 5) . The 2 SARS -CoV -2 vaccine 
candidates that will be tested in this study  are therefore:
BNT162b1 (variant RBP020.3) : nucleoside -modified messenger RNA (modRNA) 
with bl unted innate immune sensor –activ ating capacity  and augmented expression 
encoding the RBD .
BNT162b2 (variant RBP020.2 ): nucleoside -modified messenger RNA (modRNA) as 
above ,but encoding P2 S.
The vaccine candidate selected for Phase 2/3 evaluation is BNT162b 2.
2.2.1. Clinical Overview
Prior to this study , given clinical data from other similarly  formulated uRNA liposomal 
vaccines from BioNTech in oncology  trials6and recent published results from clinical trials 
using modRNA influenza vaccines by Moderna ,7the BNT162 vaccines were expected to 
have a favorable safet y profile with mild, localized ,and transient effects. BNT162 vaccines 
based on modRNA have now been administered to humans for the first time in this study  and 
the BNT162 -01study conducted in German y by BioNTech, at doses between 1 µg and 
100µg. The currently  availa blesafety  and immunogenicity  data are presented in the BNT162 
IB.
2.3.Benefit/Risk Assessment
There is an ongoing global pandemic of COVID -19 with no preventative or ther apeutic 
options available. While there were no data available from clinical trials on the use of 
BNT162 vaccines in humans at the outset of this study , available nonclinical data with these 
vaccines, and data from nonclinical studies and clinical trials w ith the same or related RNA 
components, or antigens, support eda favorable risk /benefit profile. Anticipated AEs after 
vaccination were expected to be manageable using routine symptom -driven standard of care 
as determined b y the investigators and, as a re sult, the profile of these vaccine candidate s
support edinitiation of this Phase 1/2 /3clinical study .
Updates as part of protocol amendment 6:
In order for the overall Phase 3 study  population to be as representative and 
diverse as possible, the inclusion of participants with known chronic stable HIV, 
HCV, or HBV infection is permitted. Individuals with chronic viral diseases are at 
increased risk for COVID -19 complications and severe disease. In addition, with 
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CT02- GSOP Clinical Protocol Template Phase 1 2 3 4 (05 December 2019)
Page 36the currently  available therapies for the irtreatment, many  individuals with chronic 
stable HIV, HCV, and HBV infections are unlikely to be at higher safet y risk as a 
participant in this vaccine study  than individuals with other chronic stable medical 
conditions.
All participants with chronic stabl e HIV disease will be included in the 
reactogenicity  subset (see Section 8.2.2 ).
Updates as part of protocol amendment 7:
The minimum age for inclusion in Phase 3 is lowered to 12 years, therefore 
allowing the inclusion of participants 12 to 15 years of age.
For individuals 12 to 15 years of age, the immune responses in this age group may  
be higher and reactogenicity  is expected to be si milar to y ounger adults 18 t o 25 
years of age. Inclusion of individuals 12 to 15 y ears of age was based upon a 
satisfactory  blinded safety  profile in participants 18 to 25 years of age .
All participants 12 to 15 years of age will be included in the reactogenicit y subset 
(see Section 8.2.2 ).
More detailed information about the known and expected benefits and risks and reasonabl y 
expected AEs of BNT162 RNA -based COVID -19 vaccine smay be found in the IB, which is 
the SRSD for this study . 
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Page 372.3.1. Risk Assessment
Potential Risk of Clinical 
SignificanceSummary of Data/Rationale for Risk Mitigation Strategy
Study Intervention : BNT162 RNA -Based COVID -19 Vaccine
Potential for local reactions (injection 
site redness,  injection site swelling, 
and injection site pain) and systemic 
events (fever, fatigue, headache, 
chills, vomiting, diarrhea, muscle 
pain, and joint pain) following 
vaccination.These are c ommo n adverse reactions seen 
with other vaccines, as noted in the FDA 
Center for Biologics Evaluation and 
Research (CBER) guidelines on toxicity 
grading scales for h ealthy adult volunteers 
enrolled in preventive vaccine clinical 
trials.8The Phase 1 study design includes the use of controlled vaccination and 
dose escalation to closely monitor and limit the rate of enrollment to ensure 
participant safety. The study emp loys the u se of a reactogenicity e-diary to 
monitor local reactions and systemic events in real time. Stopping rules are 
also in place. The first 5 participant s in each group in Phase 1 will be 
observed for 4 hours after vaccination to assess any immediate AEs. All 
other participants will be observed for at least 30 minutes after vaccination.
Unknown AEs and laboratory 
abnormalities with a novel vaccine.This study is one of the first 2 
parallel -running clinical studies with the 
BNT162 vaccine candidates and as such 
there areno clinical data available for t his 
vaccine.The Phase 1 study design includes the use of controlled vaccination and 
dose escalation to closely monitor and limit the rate of enrollment to ensure 
participant safety. An IRC (in Phase 1) and DMC (throughout the study) 
will also review safety data. Stopping rules are also in place. The first 5 
participants in each group in Phase 1 will be observed for 4 hours after 
vaccination to assess any immediate AEs. All other participants will be 
observed for at least 30 minutes after vaccination.
Potential for COVID -19
enhancement.Disease enhancement has been seen 
following vaccination with respiratory 
syncytial virus (RSV ),feline coronavirus ,
and Dengue virus vaccines .Phase 1 excludesparticipant s with likely previous or current COVID -19.In 
Phase 2/ 3, temporary delay criteria defer vaccination of participants with 
symptoms of potential COVID -19.All participants are follow ed for any 
potential COVID -19 illness ,including markers of severity , and h ave blood 
samples taken for potential measurement of SARS -CoV -2 antigen -specific 
antibody and SARS -CoV -2 neutralizing titers .
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Page 38Potential Risk of Clinical 
SignificanceSummary of Data/Rationale for Risk Mitigation Strategy
Study Procedures
Participant s will be required to attend 
healthcare facilities during the g lobal 
SARS -CoV-2 pandemic.Without appropriate social distancing and 
PPE, there is a potential for increased 
exposure to SARS -CoV -2.Pfizer w ill work with sites to ensure an appropriate COVID -19 prevention 
strategy. Potential COVID -19 illness visits can be conducted via t elehealth , 
without the need for an in -person visit, if required, w ith the participant 
performing a self -swab.
Venipuncture will be performed 
during the study.There is the risk of bleeding, bruising, 
hematoma formation, and infection at the 
venipuncture site.Only appropria tely qualified personnel would obtain the blood draw .
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Page 392.3.2. Benefit Assessment
Benefit s to individual participants may include:
Receipt of apotentiall y 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 risk to participants participating in this 
study , the potential risks identified in association with BNT162 RNA -based COVID -19 
vaccine are justified b y the anticipated benefits that may  be afforded to heal thy participants.
3.OBJECTIVES , ESTIMANDS ,AND ENDPOINTS
3.1.For Phase 1
Objectives Estimands Endpoints
Primary: Primary: Primary: 
To describe the safety and tolerability 
profiles of prophylactic BNT162 
vaccines in healthy adults after 1or 2 
dosesIn participants receiving at least 1 dose 
of study intervention , 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
 Adverse events (AE s) from 
Dose 1 to1 month a fter the last 
dose
 Serious AEs (SAE s) from Dose 1 
to 6 months after the last dose 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
In addition, the percentage of 
participants with:
 Abnormal hematology and 
chemistry laboratory values 1 and 
7 days after Dose 1; and 7 days 
after Dose 2
 Grading shifts in hematology and 
chemistry laboratory assessments
between baseline and 1 and 7 days 
after Dose 1; and before Dose 2 
and 7 days after Dose 2Hematology and chemistry laboratory 
parameters detailed in Section 10.2
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Page 40Objectives Estimands Endpoints
Secondary: Secondary: Secondary: 
To describe the immune responses 
elicited by prophylactic BNT162 
vaccines in healthy adults after 1or 2 
dosesIn participants complying with the key 
protocol criteria (evaluable 
participants) at the following time 
points after receipt of study 
intervention :7 and 21 days after Dose 
1; 7and 14 days and1, 6, 12 ,and 24
months after Dose 2
 Geometric mean titers (GMTs) at 
each time point
 Geometric mean fold rise (GMFR) 
from before vaccination to each 
subsequent time point after 
vaccination
 Proportion of participants 
achieving ≥4-fold rise from before 
vaccination to each subsequent 
time point after vaccinationSARS -CoV -2neutralizing titers
 Geometric mean concentrations 
(GMCs) at each time point
 GMFR from prior to first dose of 
study intervention to each 
subsequent time point
 Proportion of participants 
achieving ≥4-fold rise from before 
vaccination to each subsequent 
time point after vaccinationS1-binding IgGlevels and RBD -
binding IgG levels
 Geometric mean ratio (GMR) , 
estimated by the ratio of the
geometric mean of SARS -CoV -2
neutralizing titers to the geometric 
mean of binding IgGlevels at 
each time point SARS -CoV -2neutralizing titers
 S1-binding IgGlevels
 RBD -binding IgGlevels
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Page 413.2.For Phase 2/3
ObjectivesaEstimands Endpoints
Prim ary Efficacy
To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19 occurring from 
7 days after the second dose in 
participants without evidence of 
infection before vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) at least 7 days after 
receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT in participants with 
no serological or virological evidence 
(up to 7days after receipt of the 
second dose) of past SARS -CoV -2 
infection
To evaluate the efficac yof 
prophylactic BNT162 b2  against 
confirmed COVID -19occurring from 
7 days after the second dose in 
participants with and without 
evidence of infection before 
vaccinationIn participants complying with the 
key protocol criteria (evalu able 
participants) at least 7 days after 
receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT
Prim ary Safety
To define the safety profile of 
prophylactic BNT162b 2in the first 
360 participants randomized (Phase 2)In participants receiving at least 1 
dose of study intervention, 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 from Dose 1 to 7 days after 
the second dose
 SAEs from Dose 1 to 7 days
after the second dose Local reactions (pain at the 
injection site, redness, and 
swelling)
 Systemic even ts (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened 
muscle pain, and new or 
worsened joint pain)
 AEs
 SAEs
To define the safety profile of 
prophylactic BNT162b 2in all 
participants randomized in Phase 2/ 3In participants receiving at least 
1 dose of study intervention, 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 from Dose 1 to 1 month 
after the second dose
 SAEs from Dose 1 to 6 months 
after the second dose AEs
 SAEs
 In a subset of at least 6000 
participants:
o Local reactions (pain at the 
injection site, redness, and 
swelling)
o Systemic events (fever, 
fatigue, headache, chills, 
vomiting, diarrhea, new or 
worsened muscle pain, and 
new or worsened joint pain)
To define the safety profile of 
prophylactic BNT162 b2in 
participants 12 to 15 years of age in 
Phase 3In participants receiving at least 
1 dose of study intervention, 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 from Dose 1 to 1 month 
after the second dose
SAEs from Dose 1 to 6 
months after the second dose Local reactions (pain at the 
injection site, redness, and 
swelling)
 Systemic events (fever, fatigue, 
headache, chills, vomiting, 
diarrhea, new or worsened 
muscle pain, and new or 
worsened joint pain)
 AEs
 SAEs
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Page 42ObjectivesaEstimands Endpoints
Secondary Efficacy
To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19 occurring from 
14days after the second dose in 
participants without evidence of 
infection before vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) at least 14days after 
receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT in participants with 
no serological or virological evidence 
(up to 14days after receipt of the 
second dose) of past SARS -CoV -2 
infection
To evaluate the efficac yof 
prophylactic BNT162 b2against 
confirmed COVID -19 occurring from 
14days after the second dose in 
participants with and without 
evidence of infection before 
vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) at least 14days after 
receipt of the second dose of study 
intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of foll ow-up based on 
central laboratory or locally 
confirmed NAAT
To evaluate the efficac yof 
prophylactic BNT162b 2against 
confirmed severe COVID -19
occurring from 7 days and from 14 
days after the second dose in 
participants without evidence of 
infection befo re vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of 
study intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]Confirmed severe COVID -19 
incidence per 1000 person -years of 
follow -up in participants with no 
serological or virological evidence (up 
to 7 days and up to 14 days after 
receipt of the second dose) of past 
SARS -CoV -2 infection
To evaluate the efficac yof 
prophylactic BNT162b 2against 
confirmed severe COVID -19
occurring from 7 days and from 14 
days after the second dose in 
participants with and without 
evidence of infection before 
vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of 
study intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]Confirmed s evere COVID -19 
incidence per 1000 person -years of 
follow -up
To describe the efficac yof 
prophylactic BNT162b 2against 
confirmed COVID -19 (according to 
the CDC -defined symptoms) 
occurring from 7 days and from 14 
days after the second dose in 
participants without evidence of 
infection before vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of 
study intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 100 0 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT in participants with
no serological or virological evidence 
(up to 7 days andup to 14 days after 
receipt of the second dose) of past 
SARS -CoV -2 infection
To describe the efficac yof 
prophylactic BNT162b 2against 
confirmed COVID -19 (according to 
the CDC -defined symptoms) 
occurring from 7 days and from 14 
days after the second dose in 
participants with and without 
evidence of infection before 
vaccinationIn participants complying with the 
key protocol criteria (evaluable 
participants) 
at least 7 days 
and
at least 14 days
after receipt of the second dose of 
study intervention:
100 × (1 –IRR) [ratio of active 
vaccine to placebo]COVID -19 incidence per 1000 
person -years of follow -up based on 
central laboratory or locally 
confirmed NAAT
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Page 43ObjectivesaEstimands Endpoints
Secondary Immunogenicity
Todemonstrate the noninferiority of 
the immune response to prophylactic 
BNT162b2 in participants 12 to 15 
years of age compared to participants 
16 to 25 years of ageGMR, estimated by the ratio of the 
geometric mean of SARS -CoV -2 
neutralizing titers in the 2 age groups 
(12-15 years of age to 16 -25 years of 
age) 1 month after completion of 
vaccinationSARS -CoV -2 neutralizing titers in 
participants with no serologic al or 
virological evidence (up to 1 month
after receipt of the second dose) of 
past SARS -CoV -2 infection
Exploratory
To evaluate the immune response 
over time to prophylactic BNT162b2 
and persistence of immune response 
in participants with and without 
serological or virological evidence of 
SARS -CoV -2infection before 
vaccinationGMC/ GMT, GMFR, and percentage 
of participants with titers greater than  
defined threshold(s), at baseline and 
1, 6, 12, and 24 months after 
complet ion of vaccination S1-binding IgGlevels and/or 
RBD -binding IgGlevels
 SARS -CoV -2 neutralizing titers
To evaluate the immune response
(non-S) to SARS -CoV -2 in
participants with and without 
confirmed COVID -19 during the 
study N-binding antibody
To describe the serological responses 
to the BNT vaccine candidate in cases 
of:
 Confirmed COVID-19
 Confirmed severe COVID -19
 SARS -CoV -2 infection without 
confirmed COVID -19 S1-binding IgGlevels and/or 
RBD -binding IgGlevels
 SARS -CoV -2 neutralizing titers
To describe the safety, 
immunogenicity ,and efficacy of 
prophylactic BNT162b2 in 
individuals with confirmed stable 
HIV disease All safety, immunogenicity, and 
efficacy endpoints described 
above
To describe the safety and 
immunogenicity of prophylactic
BNT162b2 in individuals 16 to 55 
years of age vaccinated with study 
intervention produced by 
manufacturing “Process 1” or 
“Process 2”b All safety endpoints described 
above
 SARS -CoV -2 neutralizing titers
a.HIV-positive participants in Phase 3 will not be included in analyses of the objectives, with the 
exception of the specific exploratory objective.
b.SeeSection 6.1.1 for description of the manufacturing process .
This protocol will use a group of internal case reviewers to determine whether certain 
investigator -reported events meet the definition of disease -related efficacy  endpoints, using 
predefined endpoint criteria . 
For those AEs that are handled as disease -related efficacy  endpoints (which may  include 
death), a DMC will conduct unblinded reviews on a regular basis throughout the trial
(seeSection 9.6).
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Page 44Any AE that is determined by  the internal case reviewers NOT to meet endpoint criteria is 
reported back to the investigator site of incidence.  Refer to Section 8.3.1.1 for instructions 
on how to report an y such AE that meets the criteria for seriousness to Pfizer Safet y.
4.STUDY DESIGN
4.1.Overall Design
This is a multicenter, multinational, Phase 1/2/3 , randomized, placebo- controlled, 
observer -blind, dose -finding, vaccine candidate– selection , and efficacy study  in healthy  
indiv idual s.
The study  consists of 2 parts. Phase 1: to identify  preferred vaccine candidate(s) and dose 
level(s); Phase 2/3: an expanded cohort an d efficacy part.  These parts, and the progression 
between them, are detailed in the schema ( Section 1.2).
The study  will evaluate the safet y, tolerability ,andimmunogenicit y of 2different 
SARS -CoV-2 R NAvaccine candidate s against C OVID -19and the efficacy  of 1 candidate :
As a 2 -dose (separated by  21 day s) schedule ;
At various different dose levels in Phase 1;
In 3 age groups ( Phase 1: 18 to 55 y ears of age, 65 to 85 y ears of age ; Phase 2/3: ≥12
years of age [stratified as 12-15, 16 -55,or >55 years of age] ).
Dependent upon safet y and/or immunogenicit y data generated during the course of this 
study , or the BioNTech study  conducted in Germany (BNT162 -01), it is possible that groups 
in Phase 1 may  be started at the next highest dose, g roups may  not be started, groups may  be 
terminated early , and /orgroups may  be added with dose levels below the lowest stated dose 
or intermed iate between the lowest and highest stated doses .
The study  is observer -blinded, as the ph ysical appearance of the investigational vaccine 
candidates and the placebo may differ. The participant, investigator, study  coordinator, and 
other site staff will be blinded. At the study  site, only  the dispenser(s)/administrator(s) are 
unblinded.
To facilitate rapid review of data in real time, sponsor staff will be unblinded to vaccine 
allocation for the participants in Phase 1.
4.1.1. Phase 1
Each group (vaccine candidate/dose level/ age group ) will comprise 15 participant s; 
12participants will be randomized to receive active vaccine and 3 to receive placebo.
For each vaccine candidate/ dose level /age group, the following apply :
Additional safet y assessments (see Section 8.2)
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Page 45Controlled enrollment (required only  for the first candidate and/or dose level studied) :
No more than 5 participants (4 active, 1 placebo) can be vaccinated on the first 
day
Thefirst 5 participants must be observed by  blinded site staff for at least 4 hours 
after vaccination for an y acute reactions
Vaccination of the remaining participants will commence no sooner than 24 hours 
after the fifth participant received his or her vaccination
Application of stopping rules
IRC review of safet y data to determine escalation to the next dose level in the 18 -to 
55-year age cohort :
Escalation between dose levels will be based on IRC r eview of at least 7 -day 
post–Dose 1 safet y data in this study  and/or the BioNTech study  conducted in 
German y (BNT162 -01)
Note that, since both candidates arebased upon the same RNA platform, dose 
escalation for the second candidate studied may be based u pon the safet y profile 
of the first candidate studied being deemed acceptable at the same , or a higher,
dose level b y the IRC
Groups of participants 65 to 85 y ears of age will not be started until safet y data for the RNA 
platform have been deemed acceptable at the same, or a higher, dose level in the 18 -to 
55-year age cohort by the I RC.
In this phase , 13groups will be studied, corresponding to a total of 195participants.
The I RC will select 1 vaccine candidate that, in Phase 1, has an established dose level per age 
group based on induction of a post–Dose 2 immune response, including neutralizing 
antibodies, which is expected to be associated with protection against COVID -19, for
progress ion into Phase 2/ 3.
4.1.2. Phase 2/ 3
On the basis of safet y and/or immunogenicit y data generated during the course of this study, 
and/or the BioNTech study conducted in Germany (BNT162 -01), 1 vaccine candidate was
selected to proceed into Phase 2/ 3. Participants in this phase will be ≥12 years of age, 
stratified as follows : 12 to 15 y ears, 16to 55 years,or >55 years. The 12- to 15 -year stratum 
will comprise up to approximately  2000 participants enrolled at selected investigational sites.
It is intended that a minimum of 40% of participants will be in the >55-year stratum.
Commencement of each age strat um w ill be based upon satisfactory  post–Dose 2 safety  and 
immunogenicit y data from the 18 -to 55 -year and 65 -to 85 -yearagegroups in Phase 1, 
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Page 46respectivel y.  The vaccine candidate selected for Phase 2/3 evaluation is BNT162b 2at a dose 
of 30µg.
Phase 2/ 3 is event -driven. Under the assumption of a true VE rate of ≥60%, after the second
dose of investigational product, a target of 164primary -endpoint cases of confirmed 
COVID -19 due to SARS -CoV -2 occurring at least 7days following the second dose of the 
primary  series of the candidate vaccine will be sufficient to provide 90% power to conclude 
true VE >30% with high probability .The total number of participants enrolled in Phase 2/ 3 
may vary depending on the incidence of COVID -19 at the time of the enrollment, the true 
underly ing VE, and a potential earl y stop for efficacy  or futility .
Assuming a COVID -19 attack rate of 1. 3%per y earin the placebo group , accrual of 164 first
primary -endpoint cases within 6 months, an estimated 20% nonevaluable rate ,and 1:1 
randomization, the BNT162b2 vaccine candidate selected for Phase 2/ 3 is expected to 
comprise approximately  21,999 vaccine recipients .This is t he number of participants 
initially  targeted for Phase 2/ 3 and may be adjusted based on advice from DMC analy ses of 
case accumulation and the percentage of participants who are seropositive at baseline.
Dependent upon the evolution of the pandemic, it is possible that the COVID -19 attack rate 
may be much higher, in which case accrual would be expected to be more rapid, enabling the 
study ’s primary  endpoint to be evaluated much sooner.
The first 360 participants enrolled (180 to active vaccine and 180 to placebo , stratified 
equally  between 18 to 55 years and >55to 85 y ears) will comprise the “Phase 2 ”portion. 
Safety  data through 7 day s after D ose 2 and immunogenicity  data through 1 month after 
Dose 2 from these 360 participants will be anal yzed by  the unblinded statistical team, 
reviewed b y the DMC, and submitted to appropriate regulatory  authorities for review. 
Enrol lment may continue during this period and these participants would be included in the 
efficacy  evaluation in the “Phase 3” portion of the study .
In Phase 3, up to approximately  2000 participants , enrolled at selected sites, are anticipated 
to be 12 to 15 y ears of age. Noninferiority  of immune response to proph ylactic BNT162b2 
in participants 12to 15 years of age to response inparticipants 16 to 25years of ag e will be 
assessed based on the GM Rof SARS -CoV -2 neutralizing titers using a 1.5 -fold margin. A 
sample size of 2 00 evaluable participants (or 250 vaccine recipients) per age group will 
provide a power of 90.8 % to declare the noninferiority in terms of GM R(lower limit of 95%
CIforGMR>0.67) . A random sample of 25 0participant s from each of the 2age group s
(12to 15 y ears and 16 to 25 y ears) will be selected as an immunogenicity  subset for the 
noninferiority  assessment.
The initial BNT162b2 was manufac tured using “Process 1”; however, “Process 2” was 
developed to support an increased scale of manufacture. In the stud y, each lot of
“Process 2”-manufactured BNT162b2 will be administered to approximately  250participants
16 to 55 y ears of age . The safet y and immunogenicity  of prophy lactic BNT162b2 in 
individuals 16 to 55 y ears of age vaccinated with “Process 1” and each lot of “Process 2” 
study  intervention will be described. A random sample of 250 participants from those 
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Page 47vaccinated with study  intervention produced by  manufacturing “Process 1” will be selected 
for this descriptive analysis .
Participants are expected to participate for up to a maximum of approximately 26 months. 
The duration of stud y follow -up may  be shorter among participants e nrolled in Phase 1 
dosing arms that are not evaluated in Phase 2/ 3. 
4.2.Scientific Rationale for Study Design
Additional surveillance for COVID -19 will be conducted as part of the study , given the 
potential risk of disease enhancement. If a participant exper iences s ymptoms, as detailed in 
Section 8.13,a COVID -19 illness and subsequent convalescent visit will occur. As part of 
these visits, samples ( nasal [midturbinate ]swab and blood) will be taken for antigen and 
antibody  assessment as well as recording of COVID -19–related clinical and laboratory  
information (including local diagnosis). 
Human reproductive safety  data are not availa blefor BNT162 RNA -based COVID -19 
vaccine s,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 ).
4.3.Justification for Dose
Because of the requirement for a rapid response to the newl y emerged COVID -19 pandemic, 
sufficient data were not available to experimentally  validate the dose selection and initial 
starting dose . Therefore, the original planned starting dose of10 µg (for both BNT162b1 and 
BNT162b2) in this study wasbased on nonclinical experience with the same RNAs encoding 
other viral antigens (such as influenza and HIV antigens). The general safety  and 
effectiveness of uRNA and modRNA platforms have been demonstrated in oncological 
clinical trials with different administration routes (NCT02410733, NCT03871348). Doses of 
up to 400 µg total uRNA have been administered IV as RNA lipo plex (RNA -LPX) and doses 
of up to 1000 µg total naked modRNA have been administered intratumorally , both without 
signs of unpredictable overstimulation of the immune sy stem.
Based on nonclinical data of the RNA components, with other liposomes or in conjun ction 
with the lipid nanoparticles as will be tested clinically  in this study , it wasexpected that 
doses in the 1 -to 5-µg range would be immunogenic and induce neutralizing antibodies;
however ,it was anticipated that 3-to 10 -fold higher doses would lik ely be required to elicit a 
stronger antibod y response. Based on previous clinical and nonclinical experience, it was 
expected that doses of up to 100 µg would be well tolerated .
Update as part of protocol amendment 2:preliminary  experience in this study and the 
BioNTech study  conducted in Germany  (BNT162 -01) suggests that, for vaccine candidates 
based on the modRNA platform, a dose level between 30 µgand 100 µgwarrants 
consideration. Therefore ,a 50-µgdose level is formally  included for BNT162b1 and 
BNT162b2.
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Page 48Update as part of protocol amendment 3: as data have become available from this study  and 
the BNT162 -01 study  in Germany , it was decided:
To not study  the BNT162a1 and BNT162c2 vaccine candidates at this time, so these 
candidates have been remove d from the protocol; and
That lower dose levels of BNT162b1 and BNT162b2 warrant consideration.  
Therefore, a 2 0-µgdose level is formall y included for both candidates.
Update as part of protocol amendment 4: the 50- µgdose level for BNT162b1 and BNT162b2 
is removed andthe 100- µgdose level for BNT162b2 is removed ; similar dose levels of 
BNT162b3 may  be studied as for BNT162b1 and BNT162b2.
Update as part of protocol amendment 5: the vaccine candidate selected for Phase 2/3 
evaluation is BNT162b 2at a dose of 30 µg.BNT162b3 will not be studied.
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 .Note that participants enrolled in Phase 1 in groups that do 
not proceed to Phase 2/ 3 may be followed for fewer than 24 months (but no less than 
6months after the last vaccination).
The end of the stud y is defined as the date of last visit of the last participant in the study .
5. STUDY POPULATION
This study  can fulfill its objectives only  if appropriate participant s are enrolled.  The 
following eligibility  criteria are designed to select participant s 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 enro llment criteria ,also 
known as protocol waivers or exemptions, is not permitted .
5.1. Inclusion Criteria
Participants are eligible to be included in the study onl y if all of the following criteria appl y:
Age and Sex :
1.Male or female participants between the ages of 18 and 55years, inclusive, and 65 and 
85years, inclusive (Phase 1) , or ≥12 years(Phase 2/3) ,at randomization. Note that 
participants <18 years of age cannot be enrolled in the EU.
Refer to Appendix 4 for reproductive criteria for male ( Section 10.4.1 ) and female 
(Section 10.4.2 ) participants.
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Page 49Type of Participant and Disease Characteristics:
2.Participants who are willing and able to compl y with all scheduled visits, vaccination 
plan, laboratory  tests, lifesty le considerations, and other study  procedures.
3.Health y participants who are determined b y medical history, ph ysical examination
(ifrequired) , 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 therap y or hospitalization for worsening disease during 
the 6 weeks before enrollment, can be included. Specific criteria for Phase 3 participants 
with k nown stable infection with human immunodeficiency  virus (HIV), hepatitis C virus 
(HCV), or hepatitis B virus (HBV) can be found in Section 10.8.
4.Phase 2/3 only: Participant swho, in the judgment of the investigator, areat higher risk 
for acquiring COVID -19 (including, but not limited to , use of mass transportation, 
relevant demographics, and frontline essential workers) .
Informed Consent:
5.Capable of giving personal signed informed consent /have parent (s)/legal guardian 
capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the I CDand in this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study  if any  of the following criteria apply :
Medical Conditions:
1.Other medical or psy chiatric c ondition 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 investig ator’s judgment, make the participant inappropriate for the 
study .
2.Phase s 1and2 only: Known infection with human immunodeficiency  virus ( HIV), 
hepatitis C virus (HCV), or hepatitis B virus (HBV).
3.History  of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphy laxis) to any  component of the study  intervention (s).
4.Receipt of medications intended to prevent COVID -19.
5.Previous clinical (based on COVID -19 symptoms/signs alone, if a SARS -CoV -2 NAAT 
result was not available) or microbiological (based on COVID -19symptoms/signs and a 
positive SARS -CoV -2 NAAT result) diagnosis of COVID -19.
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Page 506.Phase 1 only :Individuals at high risk for severe COVID -19, including those with any  of 
the following risk factors:
Hypertension
Diabetes mellitus
Chronic pulmonary  disease
Asthma
Current vaping or smoking
History  of chronic smoking within the prior y ear
Chronic liver disease
Stage 3 or worse chronic kidney  disease (glomerular filtration rate 
<60mL/min/1.73 m2)
Resident in a long -term facility
BMI >30 kg/m2
Anticipating the need for immunosuppressive treatment within the next 6 months
7.Phase 1 only :Individuals currentl y working in occupations with high risk of exposure to 
SARS -CoV -2 (eg, healthcare worker, emergency  response personnel).
8.Immunocompromised individuals with know n or suspected immunodeficiency , as 
determined b y history  and/or laboratory /physical examination.
9.Phase 1 only :Individuals with a history  of autoimmune disease or an active autoimmune 
disease requiring therapeutic intervention, including but not limited t o: sy stemic or 
cutaneous lupus ery thematosus, autoimmune arthritis/rheumatoid arthritis, Guillain -Barré 
syndrome, multiple sclerosis, Sjögren’s s yndrome, idiopathic thrombocytopenia purpura, 
glomerulonephritis, autoimmune thy roiditis, giant cell arteritis (temporal arteritis), 
psoriasis, and insulin -dependent diabetes mellitus (type 1).
10. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
11.Women who are preg nant or breastfeeding.
Prior/Concomitant Therapy:
12.Previous vaccination with any coronavirus vaccine.
13.Individuals who receive treatment with immunosuppressive therapy , including cy totoxic 
agents or s ystemic corticosteroids, eg, for cancer or an autoimmune d isease, or planned 
receipt throughout the study .  If s ystemic corticosteroids have been administered short 
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Page 51term (<14 day s) for treatment of an acute illness, participants should not be enrolled into 
the study  until corticosteroid therapy has been discontin ued for at least 28 day s before 
study  intervention administration.  I nhaled/nebulized (except for participants in 
Phase 1 – see exclusion criterion 14), intra -articular, intrabursal, or topical (skin or ey es) 
corticosteroids are permitted.
14.Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
15.Receipt of blood/plasma products or immunoglobulin, from 60 day s before study  
intervention administration or planned receipt throughout the stud y.
Prior/Concurrent Clinical Study Experience:
16.Participat ion in other studies involving study  intervention within 28 day s prior to study  
entry  and/or during study participation.
17.Previous participation in other studies involving study  intervention containing lipid 
nanoparticles.
Diagnostic Assessments:
18.Phase 1 only:Positive serological test for SARS- CoV -2 IgM and/or IgG antibodies at 
the screening visit.
19.Phase 1only: Any screening hematology and/or blood chemistry laboratory value that 
meets the definition of a ≥Grade 1 abnormality .
Note: With the exception of bilirubin, participants with any  stable Grade 1 abnormalities 
(according to the toxicity  grading scale) may  be considered eligible at the discretion of 
the investigator.  (Note: A “stable” Grade 1 laboratory  abnormalit y is defined as a report 
of Grade 1 on an initial blood sample that remain s ≤Grade 1 upon repeat testing on a 
second sample from the same participant.)
20.Phase 1only: Positive test for HIV, hepatitis B surface antigen (HBsAg), hepatitis B 
core antibodies (HBc Abs), or he patitis C virus antibodies (HCV Abs) at the screening 
visit.
21.Phase 1 only: SARS -CoV -2 NAAT -positive nasal swab within 24 hours before receipt of 
study  intervention.
Other Exclusions:
22. Investigat orsite staff or Pfizer /BioNTech employees directly  involved in the conduct of 
the study , site staff otherwise supervised by  the investigator, and their respective famil y 
members .
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Page 525.3.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 
(seeAppendix 4 ,Section 10.4.4 )and will confirm that the participant has been instructed in 
its consistent and correct use.  At time points indicated in the SoA, the investigator or 
designee wi ll inform the participant of the need to use highl y effective contraception 
consistently  and correctly  and document the conversation and the participant’s affirmation in 
the participant ’s chart ( participant s 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  
authorities. Minimal information includes demograp hy, screen failure details, eligibility  
criteria, and an y SAE.
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/Ra ndomization/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.
1.Current febrile illness ( body tempera ture ≥100.4 °F [≥38°C]) or other acute illness within 
48 hours before study  intervention administration. This includes c urrent s ymptoms 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 l oss of taste/smell;
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Page 53Sore throat;
Diarrhea;
Vomiting.
2.Receipt of an y seasonal or pandemic influenza vaccine within 14 day s, or any  other 
nonstudy  vaccine within 28 days,before study  intervention administration.
3. Anticipated receipt of any seasonal or pandemic influenza vaccine within 14 day s, or any  
other nonstudy  vaccine within 28 day s,after study  intervention administration.
4.Receipt of short -term (<14 day s) systemic corticosteroids.  Study  intervention
administ ration should be delay ed until sy stemic corticosteroid use has been discontinued 
for at least 28 day s.  Inhaled/nebulized, intra -articular, intrabursal, or topical (skin or 
eyes) corticosteroids are permitted.
6.STUDY INTERVENTION
Study  intervention is defin ed as an y 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.
The study  will evaluate a 2-dose (separated b y 21 days) sc hedule of various different dose 
levels of 2 investigational RNA vaccine candidate s for active immunization against 
COVID -19in 3 age groups ( 18 to 55 years of age ,65 to 85 y ears of age ,and≥12years of 
age[stratified as 12-15, 16 -55,or >55 years of age] ).
These 2 investigational RNA vaccine candidate s, with the addition of saline placebo, are the 
3potential study  interventions that may  be administered to a study  participant:
BNT162b1 (BNT162 RNA -LNP vaccine utilizing m odRNA and enco ding the RBD ): 
10µg, 20µg, 30µg, 100 µg
BNT162b2 (BNT162 RNA -LNP vaccine utilizing m odRNA and encoding the P2 S ): 
10µg, 20µg, 30µg
Normal s aline (0.9% s odium chloride solution for i njection )
The vaccine candidate selected for Phase 2/3 evaluation is BNT162b 2at a dose of 30µg.
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Page 546.1.Study Intervention(s) Administered
Intervention Name BNT162b1 
(BNT162 RNA -LNP 
vaccine utilizing 
modRNA)BNT162b2 
(BNT162 RNA -LNP 
vaccine utilizing 
modRNA)Saline Placebo
Type Vaccine Vaccine Placebo
Dose Form ulation modRNA modRNA Normal saline (0.9% 
sodium chloride solution 
for injection)
Unit Dose Strength(s) 250 µg/0.5 mL 250 µg/0.5 mL N/A
Dosage Level(s)a10-, 20-, 30-, 100 -µg 10-, 20-, 30-µg N/A
Route of Adm inistration Intramuscular injection Intramuscular injection Intramuscular injection
Use Experimental Experimental Placebo
IMP or NIMP IMP IMP IMP
Sourcing Provided centrally by the 
sponsorProvided centrally by the 
sponsorProvided centrally by the 
sponsor
Packaging and Labeling Study intervention will be 
provided in a glass vial as 
open -label supply. Each 
vial will be labeled as 
required per country 
requirementStudy intervention w ill be 
provided in a glass vial as 
open -label supply. Each 
vial will be labeled as 
required per country 
requirementStudy intervention will be 
provided in a glass or 
plastic vial as open -label 
supply. Each vial will be 
labeled as required per 
country requi rement
a.Dependent upon safety and/or immunogenicity data generated during the course of this study, or the 
BioNTech study conducted in Germany (BNT162 -01), it is possible that groups may be started at the next 
highest dose, groups may not be started, groups may be terminated early, and/or groups may be added 
with dose levels below  the lowest stated dose or intermediate betw een the lowest and highest stated doses .
The vaccine candidate selec ted for Phase 2/3 evaluation is BNT162b 2at a dose of 30µg.
6.1.1. Manufacturing Process
The scale of the BNT162b2 manufacturing has been increased to support future supply .  
BNT162b2 generated using the manufacturing process supporting an increased supply  
(“Process 2 ”) will be administered to approximately 250 participants 16 to 55 y ears of age, 
per lot, in the study .The safet y and immunogenicity  of proph ylactic BNT162b2 in 
individuals 16 to 55 y ears of age vaccinated with material generated using the exist ing 
manufacturing process “Process 1 ,” and with material from lots generated using the 
manufacturing process supporting increased supply, “Process 2,” will be described.
In brief, the process changes relate to the method of production for the DNA template that 
RNA drug substance is transcribed from, and the RNA drug substance purification method.   
The BNT162b2 drug product is then produced using a scaled -up LNP manufacturing process.
6.1.2. Administration
Participants will receive 1 dose of study  intervention as r andomized at each vaccination visit 
(Visits 1 and 4 for Phase 1 participants, Visits 1 and 2 for Phase 2/3 participants) in 
accordance with the study’s SoA.The volume to be administered may  vary  by vaccine 
candidate and dose level; full details are described in the I P manual.
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Page 55Study  intervention should be administered intramuscularl y into the deltoid muscle , preferabl y
of the nondominant arm ,by an unblinded administrator .
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 b y an appropriately  qualified, 
GCP -trained, and vaccine- experienced member of the study  staff (eg, ph ysician, 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  intervention sreceived and an y discrepancies are 
reported and resolved before use of the stud y intervention.
2.Only  participants enrolled in the study  may  receive study  intervention and only  
authorized site staff may  supply  or administ er study  intervention. All study interventions
must be stored in a secure, environmentall y controlled, and monitored (manual or 
automated recording ) area in accordance with the labeled storage conditions with access 
limited to the investigator and authori zed site staff.  At a minimum, daily  minimum and 
maximum temperatures for all site storage locations must be documented and available 
upon request.  Data for nonworking day s must indicate the minimum and maximum 
temperature ssince previously  documented forall 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 an y actions taken.  The site should actively  pursue 
options for returning the st udy 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 d etails 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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Page 567. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for stud y intervention accountability , reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records) , such as the IPAL or 
sponsor -approved equivalent . All study  intervention swill 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 I P manua l.All destruction must be adequatel y documented.  If 
destruction is authorized to take place at the investigator site, the investigator must ensure 
that the materials are destroy ed in compliance with applicable environmental regulations, 
institutional policy , and any  special instructions provided by  Pfizer.
Upon identification of a product complaint, notify the spon sor w ithin 1 business day  of 
discovery  as described in the I P 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 b y an appropriatel y
qualified and experienced member of the stud y staff (eg, ph ysician, nurse, phy sician’s 
assistant, nurse practitioner, pharmacy  assistant/technician, or pharmacist) as allowed b y 
local, state, and institutional guidance.   A second staff member will verify  the dispensing.
Study  intervention and placebo will be prepared by qualified unblinded site personnel 
according to the IP manual.  The study  intervention will be administered in such a way to 
ensure the participant sremain blinded .
6.3.Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Allocation (randomiz ation) of participants to vaccine groups will proceed through the use of 
an IRT s ystem (I WR).  The site personnel (study coordinator or specified designee) will be 
required to enter or select information including but not limited to the user’s I D and 
password, the protocol number, and the participant number.  The site personnel will then be 
provided with a vaccine assignmen t and randomization number.  The IRT sy stem 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 -speci fic IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT s ystem.
6.3.2. Blinding of Site Personnel
In this observer blinded study , the study  staff receiving, storing, dispensing, preparing, and 
administering the stud y interventions will be unblinded.  All other study  and site personnel, 
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Page 57including the investigator, investigator staff, and participants ,will be blinded to study  
intervention assignments.  I n particular, t he individuals who evaluate participant safet y will 
be blinded.  Because the BNT162 RNA -based COVID -19 vaccine candidates and placebo
are different in phy sical appearance, the study  intervention syringes will be administered in a 
manner that prevents the study  participants from identify ing the study  intervention type based 
on its appearance.
The responsibility  of the unblinded dispenser and administrator must be assigned to an 
individual or individuals who will not participate in the evaluation of an y study participants.  
Contact between the unblinded dispenser and study participants and unblinded administrator 
and study  participants should be kept to a minimum.  The remaining site personnel must not 
know study  intervention assignments.
6.3.3. Blinding of the Spons or
To facilitate rapid review of data in real time, sponsor staff will be unblinded to study  
intervention allocation for the participants in Phase 1.The majorit y of sponsor staff will be 
blinded to study  intervention allocation in Phase 2/ 3. All laborat ory testing personnel 
performing serology  assay s will remain blinded to study  intervention assigned/received 
throughout the stud y.The following s ponsor staff , who will have no part in the blinded 
conduct of the stud y,will be unblinded in Phase 2/3 (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 arenot direct member sof the study  team and will not 
participate in an y other study -related activities, will review unblinded protocol 
deviations.
An unblinded team supporting interactions with, and anal yses for, the DMC 
(seeSection 9.6 ). This will comprise a statistician, programmer(s), a clinical 
scientist, and a medical monitor who will review cases of severe COVID -19 as they  
are received , and will review AEs at least weekl y for additional potential cases of 
severe COVID -19(see Section 8.2.3 ).
An unblinded submissions team will be responsible for preparing unblinded anal yses 
and documents to support regulatory  activities that may  be required while the study  is 
ongoing. This team will only  be unblinded at the group level and not have access to 
individual participant assignments. The programs that produce the summary  tables 
will be developed and validated by  the blinded study  team, and these programs will 
be run b y the un blinded DMC team .The submissions team will not have access to 
unblinded COVID -19 cases unless efficacy  is achieved in either an interim anal ysis or 
the final anal ysis,as determined by  the DMC.
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Page 586.3.4. Breaking the Blind
The I RT 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 safet y must always be the first 
consideration in making suc h 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 I RT ref erence manual and IP manual will provide the contact information 
and further details on the use of the IRT s ystem.
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 stud y intervention and study participant identification will be confirmed at the
time of dosing b y a member of the stud y 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 day s prior to study  enrollment until the 6- month 
follow -up visit (Visit 8 for Phase 1 participants, and Visit 4 for Phase 2/ 3 
participants) . 
Prohibited medications listed in Section 6.5.1will be recorded ,to include start and 
stop date s, name of the medication, dose, unit, route ,and frequency .
In addition, for participants enrolled in Phase 1, all current medication at baseline will 
be recorded, to include start date, 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 anal ysisfrom that point onwards, 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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Page 59Unless considered medically  necessary , no vaccines other than study  intervent ionshould be 
administered within 28 day s before and 28 day s after each study  vaccination . One exception 
to this is that seasonal and pandemic influenza vaccine can be given at least 14 day s after, or 
at least 14 day s prior to, the administration of study intervention .
Receipt of chronic s ystemic treatment with known immunosuppressant medications, or 
radiotherap y, within 6 0 day sbefore enrollment through conclusion of the study .
Receipt of s ystemic corticosteroids (≥ 20 mg/day  of prednisone or equivalent) f or ≥14 day s is 
prohibited from 28 day s prior to enrollment to Visit 7for Phase 1 participants, and Visit 3 for 
Phase 2/ 3 participants) . 
Receipt of inhaled/nebulized corticosteroids from 28 day s prior to enrollment to Visit 7 
(1-month follow -up visit) for Phase 1 participants.
Receipt of blood /plasma products or immunoglobulins within 6 0 day sbefore enrollment 
through conclusion of the study . 
Receipt of an y other (nonstudy ) coronavirus vaccine at any  time prior to or during study  
participation is prohi bited.
Prophy lactic antipy retics 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 antipy retic or pain- relieving properties, 
it should not be withheld prior to study  vaccination.
6.5.2. Permitted During the Study
The use of antip yretics 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 (except in Phase 1 participants –see Section 6.5.1 ), topical, or localized injections of 
corticosteroids (eg, intra -articular or intrabursal administration) are permitted.
6.6. Dose Modification
This protocol allows some alteration of vaccine dose for individual participants and/or dose 
groups from the currently  outlined dosing schedule. For reasons of reactogenicity , 
tolerability , or safet y, the I RC may  recommend to reduce the second dose of study  
intervention and/ or increase the interval between doses.
If, due to a medication error, a participant receives 1 dose of BNT162b2 at Visit 1 and 1 dose 
of placebo at Visit 2 (or vice versa), the participant should be offered the possibility  to 
receive a second dose of BNT162b2 at an unscheduled visit. In this situation :
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Page 60Obtain informed consent for administration of the additional dose.
Measure the participant’s body  temperature.
Perform urine pregnancy test on WOCBP as described in Section 8.2.6.
Discuss contraceptive use as described in Section 10.4 .
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 preferabl y nondominant arm.  Please refer to the I P 
manual for further instruction on this process.
Blinded site staff must observe the participant for at least 30 minutes after study  
intervention administration for an y acute reactions.  Record an y 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.
The participant should continue to adhere to the normal visit schedule but must be 
followed for nonserious AEs for 1 month and SAEs for 6 months after the second 
dose of BNT162b2. This will require AEs to be elicited either b y unscheduled 
telephone cont act(s) and/or in -person visit(s).
6.7.Intervention A fter the End of the Study
No intervention will be provided to study participants at the end of the study .
7.DISCONTINUATION OF S TUDY INTERVENTION AN D PARTICIPANT 
DISCONTINUATION/WITH DRAWAL
7.1.Discontinuation of St udy Intervention
In rare instances, it may  be necessary  for a participant to permanentl y discontinue study  
intervention (definitive discontinuation) . Reasons for definitive discontinuation of study
intervention may 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 secon d dose, or the participant does not wish to receive it, it is preferred 
that the second dose be administered. Note that a positive SARS -CoV -2 NAAT result 
without sy mptoms does not meet exclusion criterion 5 and should not result in 
discontinuation of study intervention , whereas a COVID -19 diagnosis does meet exclusion 
criterion 5 and should result in discontinuation of study  intervention (see Section 8.15).
Note that discontinuation of study  intervention does not represent withdrawal from the stud y.
Per the study  estimands, if study  intervention is definitively  discontinued, the participant will 
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Page 61remain in the study  to be evaluated for safety , immunogenicity ,and efficacy .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 m edical records whether the participant is discontinuing further 
receipt of stud y intervention or also from study  procedures, posttreatment study  follow -up, 
and/or future collection of additional information.
7.2.Participant Discontinuation/ Withdrawal F rom the Study
A participant may  withdraw from the study  at an y time at his/her own request.  Reasons for 
discontinuation from the study  may include the following:
Refused further follow -up;
Lost to follow -up;
Death ;
Study  terminated by  sponsor ;
AEs;
Participant re quest; 
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.  I n 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 partici pants.
If a participant withdraws from the study , he/she may  request destruction of any  remaining 
samples taken and not tested, andthe 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 an y of the withdrawal/earl y termination procedures w ill not be 
viewed as protocol deviations so long as the participant ’s safet y was preserved.
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Page 627.2.1. Withdrawal of Consent
Participant s 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 onl y 
exception to this is when a participant specificall y withdraws consent for any further contact 
with him or her or persons previously  authorized by  the participant to provide this 
information.  Participant s 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 posttreatment s tudy 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 
inaccordance with local law.
7.3.Lost to Fol low-up
A participant will be considered lost to follow- up if he or she repeatedl y fails to return for 
scheduled visits and is unable to be contacted b y the study  site.
The following actions must be taken if a particip ant 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 
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 ne cessary , 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 co nsidered 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 criticall y evaluate the immune response and safet y 
profile b y age.
Study  procedures and their timing are summarized in the SoA. Protocol waivers or
exemptions are not allowed.
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Page 63Safety  issues should be discussed w ith the sponsor immediately  upon occurrence or 
awareness to determine whether the participant should continue or discontinue study  
intervention.
Adherence to the stud y design requirements, including those specified in the SoA, is ess ential 
and required for stud y 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 scre ened 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 m ay be 
circumstances outside the control of the investigator that may  make it unfeasible to perform 
the test.  I n these cases, the investigator must take all steps necessary  to ensure the safet y and 
well-being of the participant.  When a protocol -required t est cannot be performed, the 
investigator will document the reason for the missed test and an y corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study  team must be informed of these incidents in a timely  manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study .
The tot al blood sampling volume for individual participant s in this study  is approximately  up 
to: 515 mL for participants in Phase 1, 110 mLfor Phase 2/ 3 participants ≥16 y ears of age ,
and 50 mL for participants in the 12- to 15-year age stratum .Additionally , 20mL of blood 
for participants ≥16 y ears of age and 10 mL for participants in the 12 -to 15-year age stratum 
will be taken at an unplanned convalescent visit at any  time a participant develops respiratory  
symptoms indicating a potential COVID -19 infection .Select participants in Phase 1 will also 
be asked to provide an additional blood sample of approximately  170 mL at either Visit 5, 6, 
or 7.  These participants would therefore have a total blood sampling volume of 700 mL  
during the 24 -month study  period . Other additional blood samples may  be taken for safet y 
assessments at times specified b y Pfizer, provided the total volume taken during the stud y 
does not exceed 550 mL during an y period of 60 consecutive day s.
8.1.Efficacy and/or Immunogenicity Assessments
Efficacy  will be assessed throughout a participant’s involvement in the study  through 
surveillance for potential cases of COVID -19. If, at an y time, a participant develops acute 
respiratory  illness ( see Section 8.13), for the purposes of the study  he or she will be 
consider edto potentiall y have COVID -19 illness.9In this circumstance, the participant 
should contact t he site , an in-person or telehealth visit should occur ,and a ssessments should 
be conduct edas specified in the SoA . The assessments will include a nasal (midturbinate) 
swab ,which will be tested at a central laboratory  using a reverse transcription–poly merase 
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Page 64chain reaction (RT- PCR) test (Cepheid; FDA approved under EUA), or other equivalent 
nucleic acid amplification –based test (ie, NAAT), to detect SARS -CoV -2. In addition, 
clinical information and results from local standard-of-care tests (as deta iled in Section 8.13)
will be assessed. The central laboratory  NAAT result will be used for the case definition, 
unless no result is available from the central laboratory , in which case a local NAAT result 
may be used ifit was obtained using 1of the following assay s:
Cepheid Xpert Xpress SARS -CoV -2
Roche cobas SARS -CoV -2 real-time RT -PCR test (EUA200009/A001)
Abbott Molecular/RealTime SARS -CoV -2 assay  (EUA200023/A001)
Two definitions of SARS -CoV -2–related cases , and SARS -CoV -2–related severe cases ,will 
be considered (for both, the onset date of the case will be the date that s ymptoms were first 
experienced b y the participant ; if new sy mptoms are reported within 4 day s after resolution 
of all previous s ymptoms, they  will be considered as part of a single illness):
Confirmed COVID -19: presence of at least 1 of the following symptom sand 
SARS -CoV -2 NAAT -positive during, or within 4days before or after, the 
symptomatic period , either at the central laboratory or at a local testing facility (using 
an acceptable test):
Fever; 
New or increased cough; 
New or increased shortness of breath; 
Chills; 
New or increased muscle pain; 
New loss of taste or smell;
Sore throat ;
Diarrhea;
Vomiting .
The second definition, which may be updated as more is learn edabout COVID -19, will 
include the following additional symptoms defined by theCDC ( listed at 
https://www.cdc.gov/coronavirus/2019 -ncov/s ymptoms- testing/sy mptoms.html) :
Fatigue;
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Page 65Headache;
Nasal congestion or runny  nose;
Nausea .
Confirmed severe COVID- 19: confirmed COVID -19 and presence of at least 1 of the 
following:
Clinical signs at rest indicative of severe s ystemic illness (RR ≥30breaths per 
minute, HR ≥125 beats per minute, SpO 2≤93% on room air at sea level, or 
PaO 2/FiO 2<300 mm Hg);
Respiratory  failure (defined as needing high -flow oxy gen, noninvasive 
ventilation, mechanical ventilation, or ECMO);
Evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring 
vasopressors);
Significant acute renal, hepatic, or ne urologic dy sfunction *;
Admission to an ICU;
Death.
The DMC may  recommend modification of the definition of severe disease according to 
emerging information.
* Three blinded case reviewers ( medicall y qualified Pfizer staff members )will review all 
potential COVID -19 illness events. If a NAAT -confirmed case in Phase 2/ 3 may  be 
considered severe, or not, solely  on the basis of this criterion, the blinded data will be 
reviewed b y the case reviewers to assess whether the criterion is met; the majority  opinion 
will prevail.
In addition, a serological definition will be used for participants without clinical presentation 
of COVID -19:
Confirmed seroconversion to SARS -CoV -2 without confirmed COVID -19: positive 
N-binding antibody  result in a participant with a prior negative N -binding antibody  
result
Serum samples will be obtained for i mmunogenicity  testing at the visits specified in the SoA.
The following assay s will be performed:
SARS -CoV -2neutralization assay
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Page 66S1-binding IgG level assay
RBD-binding IgG level assay
N-binding antibody  assay
Note that all immunogenicity  analy ses will be based upon samples anal yzed at the central 
laboratory ; the rapid test will only  be performed at screening b y all sites recruiting 
participants in Phase 1 (see Section 8.11.1.1 )to determine eligibility .
Serum obtained from the additional ~170- mL blood sample from select participants in Phase
1 at either Visit 5, 6, or 7 will be used for exploratory  COVID -19 research, intended to 
establish a surrogate endpoint that is reasonably  likely  to predict clinical benefit.
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 assay s outlined in the protocol 
may be stored by  Pfizer.  Unless a time limitation is required b y local regulations or ethical 
requirements, the samples will be stored for up to 15 y ears after the end of the study  and then 
destroy ed.  If allowed by  the I CD, 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 DNA will be performed. 
The participant may request that his or her samples, if still identifiable, be destroy ed at any  
time; however, an y data alread y collected from those samples will still be used for this 
research.  The biological samples may  be shared with other researchers as long as 
confidentiality  is maintained and no testing of the participant’s DNA is performed .
8.2.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 stud y to assess any 
perceived safety  issues.
A clinical assessment, including medical history ,will be performed on all participant s at 
his/her first visit to establish a baseline. Significant medical history  and observations from 
any phy sical 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 4 hours after administration of the study  intervention (for the 
first 5 participants vaccinated in each Phase 1 group), and within the first 30 minutes (for the 
remainder of participants), will be assessed and documented in the AE CRF.
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Page 67The safet y parameters also include reactogenicit y e-diary  reports of local reactions and 
systemic events (including fever) , and use of antipy retic medication that occur in the 7 days 
after administration of the study  intervention in a subset of participants .  These prospectively  
self-collected occurrences of local reactions and sy stemic events are graded as described in
Section 8.2.2 .For pa rticipants who are not in the reactogenicity  subset, these local reactions 
and sy stemic events should be detected and reported as AEs, in accordance with 
Section 8.3.2 .
8.2.1. Clinical Safety Laboratory Assessments (Phase 1 Participants Only)
See Appendix 2 for the list of clinical safet y laboratory  tests to be performed and the SoAfor 
the timing and frequency. All protocol -required laboratory  assessments, as defined in 
Appendix 2 , must be conducted in accordance with the laboratory  manual and the SoA. 
Unscheduled clinical laboratory  measurements may  be obtained at any  time during the study  
to assess an y perceived safet y issues.
The investigator must review the laboratory  report, document this review, and record any  
clinically  relevant changes occurring during the study  in the AE section of the CRF. See 
Appendix 2 for the grading scale for assessment of clinically  significant abnormal laboratory  
findings. Clinically  significant abnormal laboratory  findings are those which are not 
associated with the underly ing disease, unless judged by  the investigator to be more severe 
than expected for the participant's condition.
All laboratory  tests with values considered clinically  significantl y abnormal during 
participation in the study  or within 28 day safter the last dose of stud y intervention should be 
repeated until the values return to normal or baseline or are no longer con sidered clinically  
significant b y the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by  
the investigator, the etiology  should be identified and the sponsor notified.
See Appendix 5 for suggested actions and follow -up assessments in the event of potential 
drug-induced liver injury (DILI) .
8.2.2. Electronic Diary
Participants will be required to complete areactogenicity e-diary through an application 
(see Section 8.14) installed on a provisioned device or on the participant’s own personal 
device. All participant s in Phase 1, and a subset of at least the first 6000 randomized in 
Phase 2/ 3, will be asked to monitor and record local reactions, sy stemic events, and 
antipy retic medication usage for 7 days following administration of the study  intervention. 
All participants in Phase 3 who are HIV -positive or 12 to 15 years of age will be included in 
this subset . In addition, participants 16 through 17 y ears of age enrolled under protocol 
amendment 9 and onwards will be included in the reactogenicity  subset .The reactogenicit y 
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 s ystemic events reported in the reactogenicit y e-diary  will be transferred 
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Page 68electronically  to a third- party  vendor, where they  will be available for review by  investigators 
and the Pfizer clinicians at all times via an i nternet -based portal. 
At intervals agreed to b y the vendor and Pfizer, these data will be transferred electronicall y 
into Pfizer's database for anal ysis 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 interva ls as part of the ongoing safet y review.
The investigator or designee must obtain stop dates from the participant for any  ongoing 
local reactions, systemic events ,or use of antipy retic medication on the last day  that the 
reactogenicity  e-diary  was complet ed.  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 Center f or Biologics Evaluation and Research 
(CBER) guidelines on toxicity  grading scales for healthy  adult volunteers enrolled in 
preventive vaccine clinical trials.8
8.2.2.2. Local Reactions
During the reactogenicit y e-diary  reporting period, participant s will be asked to assess 
redness, swelling, and pain at the injection site and to record the s ymptoms in the 
reactogenicity  e-diary .  If a local reaction persists bey ond 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: 1to21) and then categorized during anal ysis 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 b y the participant as absent, mild, moderate, or severe 
according 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 medicall y 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 immedi ately  notify  the sponsor and, if it is determined to be 
related to the administration of the study  intervention , further vaccinations will b e 
discontinued in that participant.
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Page 69Table 1.Local Reaction Grading Scale
Mild 
(Grade 1)Moderate 
(Grade 2)Severe 
(Grade 3)Potentially Life 
Threatening 
(Grade 4)
Pain at the 
injection siteDoes not interfere 
with activityInterferes with 
activityPrevents daily activity Emergency room visit 
or hospitalization for 
severe pain
Redness >2.0cm to 5.0 cm 
(5 to 10 measuring 
device units)>5.0 cm to 10.0 cm 
(11 to 20 measuring 
device units)>10cm 
(≥21measuring 
device units)Necrosis or 
exfoliative dermatitis
Swelling >2.0cm to 5.0 cm 
(5 to 10 measuring 
device units)>5.0 cm to 10.0 cm
(11 to 20 measuring 
device units)>10cm 
(≥21measuring 
device units)Necrosis
8.2.2.3. Systemic Events
During the reactogenicit y e-diary  reporting period, participant s will be asked to assess 
vomiting, diarrhea, headache, fatigue, chills, new or worsen edmuscle pain, and new or 
worsen ed joint pain and to record the s ymptoms in the reactogenicit y e-diary .  The s ymptoms 
will be assessed b y the participant as absent, mild, moderate, or severe according to the 
grading scale in Table 2.
If a Grade 3 s ystemic event is reported in the reactogenicity  e-diary ,a telephone contact 
should occur to ascertain further details and determine whether a site vi sit is clinically  
indicated.  Only an investigator or medicall y qualified person is able to cla ssify  a 
participant’s s ystemic event as Grade 4. If a participant experiences a confirmed Grade 4 
systemic event , the investigator must immediately notify  the s ponsor 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)
Vom iting 1-2 times in 
24hours>2 times in 
24hoursRequires IV 
hydrationEmergency room visit or 
hospitalization for 
hypotensive shock
Diarrhea 2 to 3 loose stools 
in 24 hours4 to 5 loose stools
in 24 hours6 or more loose 
stools in 24 hoursEmergency room visit or 
hospitalization for severe
diarrhea
Headache Does not interfere 
with activitySome interference 
with activityPrevents daily 
routine activityEmergency room visit or 
hospitalization for severe 
headache
Fatigue/ 
tirednessDoes not interfere 
with activitySome interference 
with activityPrevents daily 
routine activityEmergency room visit or 
hospitalization for severe 
fatigue
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Page 70Table 2.Systemic Event Grading Scale
Mild 
(Grade 1)Moderate 
(Grade 2)Severe 
(Grade 3)Potentially Life 
Threatening 
(Grade 4)
Chills Does not interfere 
with activitySome interference 
with activityPrevents daily 
routine activityEmergency room visit or 
hospitalization for severe 
chills
New or 
worsen ed
muscle painDoes not interfere 
with activitySome interference 
with activityPrevents daily 
routine activityEmergency room visit or 
hospitalization for severe 
new or w orsen edmuscle 
pain
New or 
worsen ed
joint painDoes not interfere 
with activitySome interference 
with activityPrevents daily 
routine activityEmergency room visit or 
hospitalization for severe 
new or w orsen edjoint pain
Abbreviation: IV = intravenous.
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 reactogenicit y e-diary in the evening dail y during the reactogenicit y e-diary  reporting 
period.  It will also be collected at an y time during the reactogenicit y e-diary  data collection 
periods when fever is suspected.  Fever is defined as an oral temperature of ≥38.0 °C 
(100.4 °F).  The highest temperature for each day  will be recorded in the reactogenicit y 
e-diary .  Temperature will be measured and recorded to 1 decimal place and then categorized 
during anal ysis according to the scale shown in Table 3.
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 visi t is clinically  
indicated.  Onl y an investigator or medicall y qualified person is able to c onfirm 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)
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Page 718.2.2.5. Antipyretic Medication
The use of antip yretic medication to treat s ymptoms associated with study  intervention 
administration will be recorded in the reactogenicity  e-diary  daily during the reporting period 
(Day  1 to Day 7).
8.2.3. Phase 1 Stopping Rules
The following stopping rules are in place for all Phase 1 participant s, based on review of AE 
data and e -diary  reactogenicity  data , until the start of Phase 2/3 or 30 day s after the last dose 
of study  intervention in Phase 1, whichever is later .These data will be monitored on an 
ongoing basis b y the investigator (or medicall y qualified designee) and sponsor in order to 
promptly  identify  and flag an y event that potentially  contributes to a stopping rule.
The sponsor study  team will be unblinded during Phase 1, so will be able to assess whether 
or not a stopping rule has been met on the basis of a participant ’s individual study  
intervention allocation.
In the event that spons or personnel confirm that a stopping rule is met, the following actions 
will commence:
The I RC will review all appropriate data.
The stopping rule will PAUSE randomization and study  intervention administration
for the impacted vaccine candidate all dose le vels and age groups.
The DMC will review all appropriate data .
For all participant s vaccinated, all other routine study  conduct activities, including 
ongoing data entry , reporting of AEs, participant reactogenicity  e-diary  completion, 
blood sample collection, and participant follow -up, will continue during the pause.
A stopping rule is met if any
 of the following rules occur after administration of 
investigational BNT162 vaccine ; data from placebo recipients will not contribute to the 
stopping rules. React ogenicity  e-diary  data confirmed by  the investigator as being entered by  
the participant in error will not contribute toward a stopping rule.
The BNT 162bRNA platform will be evaluated for contribution to stopping rules overall ; 
vaccine candidate dose levels within theplatform and age groups will contribute to stopping 
rules together .  However, it is possible that the recommendations may  include halting or 
continuing randomization with any of the BNT162 vaccine candidates .
Stop ping Rule C riteria for Each BNT162 Vaccine Candidate :
1.If any participant vaccinated with the BNT162 candidate (at an y dose level) develops an 
SAE that is assessed by the investigator as possibly related, or for which there is no 
alternative, plausible, att ributable cause.
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Page 722.If any participant vaccinated with the BNT162 candidate (at any  dose level) develops a 
Grade 4 local reaction or sy stemic event after vaccination (see Section 8.2.2 ) that is 
assessed as possibl y related by the investigator, or for which there is no alternative, 
plausible, attributable cause.
3.If any participant vaccinated with the BNT162 candidate (at an y dose level) develops a 
fever >40.0 °C (>104.0° F) for at least 1 daily  measurement after vaccination 
(seeSection 8.2.2.4 )that is assessed as possibly  related by  the investigator, or for which 
there is no alternative, plausible, attributable cause.
4.If any 2 participants vaccinated with the BNT162 candidate (at any  dose level) report the 
same or similar severe (Grade 3) AE (including laboratory  abnormalities) after 
vaccination, assessed as possibly  related by  the investigator, or for which there is no 
alternative, plausible, attributable cause.
5.If any participant dies or requires ICU admission due to SARS -CoV -2 infection; if this 
stopping rule is met, all available clinical and preclinical safet y and immunogenicity data 
should be reviewed to evaluate for enhanced COVID -19.
8.2.4. Surveillance of Events That Could Represent Enhanced COVID -19 and Phase 2/3
Stopping Rule
Participants in all phases of the study  will be surveilled for potential COVID -19 illness from 
Visit 1 onwards (see Section 8.13).
As this is a sponsor open- label study  during Phase 1 , the sponsor willconduct unblinded 
reviews of the data during the course of the study , including for the purpose of safety  
assessment .All NAAT- confirmed cases in Phase 1 will be reviewed contemporaneousl y by 
the IRC and the DMC ( see Section 9.6).
In Phase 2/3, the unblinded team supporting the DMC , including an unblinded medical 
monitor, will review cases of severe COVID -19 as they  are received and will review AEs at 
least weekl y for additional potential cases of severe COVID -19. At an y point ,the unblinded 
team m ay discuss with the DMC chair whether the DMC should review cases for an adverse 
imbalance of cases of COVID -19 and/or severe COVID -19 between the vaccine and placebo 
groups.
The purpose of these reviews will be to identify  whether any  features of each case appear 
unusual, in particular greater in severity, compared to available information at the time of 
review.  Indicators of severity  may  include accelerated deterioration, need for hospitalization, 
need for ventilation, or death.  Observed rates of the se indicators will be compared with what 
could be expected in a similar population to the study  participants based upon available 
information at the time of review.
Stopping and alert rules will be applied as follows. The stopping rule will be triggered when 
the 1- sided probability  of observing the same or a more extreme case split is 5% or less when 
the true incidence of severe disease is the same for vaccine and placebo participants, and alert 
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Page 73criteria are triggered when this probability  is less than 11% . In addition, when the total 
number of severe cases is low (15 or less), the unblinded team supporting the DMC will 
implement the alert rule when a reverse case split of 2:1 or worse is observed. For example, 
at 3 cases 2:1, at 4 cases 3:1, etc. Below 15 cases, this rule is more rigorous than requiring 
the probability  of an observed adverse split or worse be <11%. Further details can be found 
inSection 10.7 .
8.2.5. Randomization and Vaccination After a Stopping Rule Is Met
Once the IRC (if in Phase 1) and DMC (all phases) have reviewed the safety  data and 
provided guidance, a notification will be sent from the sponsor to the sites with guidance on 
how to proceed.
8.2.6. Pregnancy Testing
Pregnancy  tests may  be urine or serum tests, but must have a sensitivity  of at least 
25mIU/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 
may also be repeated if requested by  IRBs/ECs or if required b y local regulations.  I n 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 f ound in Appendix 3 .
AEswill be reported b y the participant (or, when appropriate, b y a caregiver, surrogate, or 
the participant's parent(s)/legal guardian ).
The investigator and an y qualified designees are responsi ble 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 classificati on as an SAE or caused the participant to discontinue 
the study  intervention (see Section 7.1).
Each participan t/parent (s)/legal guardian will be questioned about the occurrence of AEs in a 
nonleading manner.
In addition, the investigator may  be requested by  Pfizer Safet y 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 /parent(s)/legal guardian
provides informed consent, which is obtained before the p articipant’s participation in the 
study  (ie, before undergoing an y stud y-related procedure and/or receiving study  
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Page 74intervention ), through and including Visit 7 for Phase 1 participants, and Visit 3 for Phase 
2/3 participants.  In addition, any  AEs occurring up to 48 hours after each subsequent blood 
draw must be recorded on the CRF.
SAEs will be collected from the time the participant /parent(s)/legal guardian provides 
informed consent to approximately  6 months after the last dos e of study  intervention (Visit 8 
for Phase 1 participants, and Visit 4 for Phase 2/ 3 participants).
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.
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 Report Form.
Investigators are not obligated to activel y seek AE sor SAE safter the participant has 
concluded study  participation .  However, if the investigator learns of an y SAE, including a
death, at an y 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 Report 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 Report Form i mmediately  
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.
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Page 758.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality  of AE sand SAE sand the 
procedures for completing and transmitting SAE reports are provided in Appendix 3 .
Care will be taken not to introduce bias when detecting AEs and/or SAEs.   Open -ended and 
nonleading verbal questioning of th e participant is the preferred method to inquire about 
AEoccurrences.
8.3.3. Follow -up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactivel y follow each 
participant at subsequent visits/contacts. For each event, the invest igator 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 .  An y information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy  findings must be submitted as soon as possible to Pfizer Safety .
Further information on follow -up procedures is given in Appendix 3 .
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by  the investigator to the sponsor of a n SAE is essential so that legal 
obligations and ethical responsibilities towards the safet y of participants and the safet y 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 safet y of a stud y intervention under clinical investigation.   The 
sponsor will co mply  with country -specific regulatory  requirements relating to safet y 
reporting to the regulatory  authorit y, IRBs/ECs, and investigators.
Investigator safety  reports must be prepared for SUSAR saccording to local regulatory  
requirements and sponsor policy  and forwarded to investigators as necessary .
An investigator who receives SUSAR sor 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  interventio nunder stud y during pregnancy  or breastfeeding and 
occupational exposure are reportable to Pfizer Safety  within 24 hours of investigator 
awareness.
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Page 768.3.5.1. 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 fa mily member or healthcare provider who has been exposed to the study  
intervention by inhalation or skin contact then exposes his female partner prior to 
or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery  (see below for information related to 
termination of pregnancy).
If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the Vaccine SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy  will be collected after the start of stud y intervention and until 6 months 
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 Report Form and EDP 
Supplemental Form. Si
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