Document text
Clinical Study Data Reviewer’s Guide
Pfizer Inc.
BioNTech SE
Study BNT162 -01
This document contains confidential information belonging to Pfizer Inc. Except as may be otherwise
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be promptly notified.
Clinical Study Data Reviewer’s Guide
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Contents
1. Introduction ................................ ................................ ................................ ....................... 4
1.1 Purpose ................................ ................................ ................................ ...................... 4
1.2 Acronyms ................................ ................................ ................................ ................... 4
1.3 Study Data Standar ds and Dictionary Inventory ................................ ................................ 4
2. Protocol Description ................................ ................................ ................................ ............ 4
2.1 Protocol Number and Title ................................ ................................ ............................ 4
2.2 Protocol Design ................................ ................................ ................................ ........... 6
2.3 Trial Desi gn Datasets ................................ ................................ ................................ .... 8
2.3.1 TA - Trial Arms ................................ ................................ ................................ .......... 8
2.3.2 TE - Trial Elements ................................ ................................ ................................ ..... 9
2.3.3 TV - Trial Visits ................................ ................................ ................................ ........ 10
2.3.4 TI - Trial Inclusion/Exclusion Criteria ................................ ................................ ........... 10
2.3.5 TS - Trial Summary ................................ ................................ ................................ ....10
3. Subject Data Description ................................ ................................ ................................ .....11
3.1 Overview ................................ ................................ ................................ ................... 11
3.2 Traceability Flow Diagram ................................ ................................ ........................... 11
3.3 Annotated CRFs ................................ ................................ ................................ ......... 12
3.4 SDTM Subject Domains ................................ ................................ .............................. 14
3.4.1 AE - Adverse Events ................................ ................................ ................................ ..15
3.4.2 CE - Clinical Events ................................ ................................ ................................ ...15
3.4.3 CM - Concomitant/Prior Medications ................................ ................................ ............ 15
3.4.5 DM - Demographics ................................ ................................ ................................ ...16
3.4.6 DS - Disposition ................................ ................................ ................................ ........ 16
3.4.7 DV - Protocol Deviations ................................ ................................ ............................ 17
3.4.8 EC - Exposure as Collected ................................ ................................ ......................... 17
3.4.9 EG - ECG Test Results ................................ ................................ ............................... 17
3.4.10 EX - Exposure ................................ ................................ ................................ ......... 17
3.4.11 FACE - Findings About Clinical Events ................................ ................................ ....... 18
3.4.12 IS - Immunogenicity Specimen Assessments ................................ ................................ 18
3.4.13 LB - Laboratory Test Results ................................ ................................ ..................... 18
3.4.14 MB - Microbiology Specimen ................................ ................................ .................... 19
3.4.15 MH - Medical History ................................ ................................ ............................... 19
3.4.16 PE - Physical Examination ................................ ................................ ......................... 19
3.4.17 RP - Reproductive System Findings ................................ ................................ ............ 19
3.4.18 SE - Subject Elements ................................ ................................ ............................... 20
3.4.19 SV - Subject Visits ................................ ................................ ................................ ...20
3.4.20 VS - Vital Signs ................................ ................................ ................................ ....... 20
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This document is confidential Page 3 of 73 3.4.21 XA - Ancillary Analysis and Visit Details ................................ ................................ ....20
3.4.22 XB - HLA Typing ................................ ................................ ................................ ....20
4. Data Conformance Summary ................................ ................................ ............................... 21
4.1 Conformance Inputs ................................ ................................ ................................ ....21
4.2 Issues Summary ................................ ................................ ................................ .......... 21
Appendix I: Inclusion/Exclusion Criteria ................................ ................................ ...................... 33
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This document is confidential Page 4 of 73 1. Introduction
1.1 Purpose
This document provides context for tabulation datasets and terminolo gy that benefit from additional
explanation beyond the Data Definitions document (define.xml ). In addition, this document
provides a summary of SDTM conformance findings
1.2 Acron yms
Acronym Translation
aCRF Annotated Case Report Form
COVID -19 Coronavirus Disease 2019
eDT Electronic Data Transfer (e.g. central lab data, ECG vendor data, PK data, etc.)
FIH first-in-human
HLA human leukocyte antigen
MedDRA Medical Dictionary for Regulatory Activities
N/A Not Applicable
P/B Prime boost
SARS -CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2
SD Single dose
SRC Safety Review Committee
TEAEs Treatment Emergent Adverse Events
WOCBP Women of childbearing potential
1.3 Study Data Standards and Dictionary Inventory
Standard or Dictionary Version s Used
SDTM •SDTM v1.4
•SDTM -IG v3.2
Controlled Terminology CDISC SDTM Controlled Terminology, 2020 -03-27
Data Definitions Define -XML v2.0
Medications Dictionary WHODRUG GLOBAL B3 March 1, 2020 ,
SNOMED 2020 -09-01, UNII 2020 -08-18, MED -RT 2020 -10-05
Medical Events Dictionary MedDRA v23.0
Other standards (optional) Vaccines Therapeutic Area User Guide v1.1
2. Protocol Description
2.1 Protocol Number and Title
Protocol Number: BNT162 -01
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This document is confidential Page 5 of 73 Protocol Title: A Multi -site, Phase I/II, 2 -Part, Dose -Escalation Trial Investigating the
Safety and Immunogenicity of Four Prophylactic SARS -CoV-2 RNA
Vaccines Against COVID -19 Using Different Dosing Regimens in Healthy
Adults
Protocol Versions: CorVAC -BNT162 -01_CTP_v1.0_2020 -03-24_final.pdf
CorVAC -BNT162 -01_CTP_v2.0_2020 -04-09_final_mod2.pdf
CorVAC -BNT162 -01_CTP_v3.0_2020 -04-17_final.pdf
CorVAC -BNT162 -01_CTP_v4.0_2020 -05-13_final_v1.2.pdf
CorVAC -BNT162 -01_CTP_v5.0_2020 -05-26_final.pdf
CorVAC -BNT162 -01_CTP_v6.0_2020 -06-09.pdf
CorVAC -BNT162 -01_CTP_v7.0_2020 -06-26_final.pdf
BNT162 -01_CTP_v8.0_2020 -07-21.pdf
BNT162 -01_CTP_v9.0_2020 -10-05_final.pdf
There were 8 amendments to the protocol. A detailed description of each amendment, with
rational e for change, is provided in the protocol v 9.0 under section 10.10. Some changes were
also implemented to align data collection and reporting in this trial with the data collection and
reporting in other trials with BNT162 vaccines candidates (to facilitate data merging). Some of
the critical changes are listed here.
• Allow the assessment of additional intermediate and low dose cohorts for BNT162b modRNA
vaccine candid ates to support identification of a suitable dose for Phase II/III evaluation.
• Allow the assessment of BNT162b1 modRNA vaccine candidate in elderly subjects, given its
favorable safety, tolerability, and immunogenicity profile in younger adults to date an d recently
available non -human primate immunogenicity data for the BNT162b1 and other modRNA
vaccine candidates.
• Plan the assessment of BNT162b2 modRNA vaccine candidate in elderly subjects.
• Allow revision of safety assessment & dose limiting toxicity crit eria.
• Add additional for blood draws for explorative biomarker/immunogenicity research purposes.
• BNT162b1 and BNT162b2 are both non -modified uridine RNAs, while BNT162a1 and
BNT162c2 are both nucleoside -modified pseudomethyl -uridine containing. This modification is
known to impact the extent of innate immune activation at a given dose level, and thus potentially
the extent of reactogenicity. Therefore, tolerability data obtained with one of the vaccine variants
of each of the se pairs may be potentially informative for the respective other one and should be
taken in consideration by the SRC for recommendations of lower or interim doses.
• Leftover blood may be used for additional biomarker analysis (blood sampling for research)
• Align diary data collection with other BNT162 studies
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This document is confidential Page 6 of 73 2.2 Protocol Design
Four different vaccines (BNT162a1, BNT162b1, BNT162b2, and BNT162c2) will be tested.
This trial has two parts. Part A is for dose ranging with dose escalation and de -escalat ion plus the
evaluation of interim dose levels. It also includes dose ranging in older subjects. Part B is dedicated to
recruit expansion cohorts with dose levels which are selected from data generated in Part A.
The vaccines BNT162a1, BNT162b1, BNT162b2 , and BNT162c2 will be administered using a P/B
regimen. The vaccine BNT162c2 will also be administered using a SD regimen.
The chosen trial design reflects discussion and advice from the Paul -Ehrlich Institute (PEI) obtained in
scientific advice meetings held in February, March, and June 2020.
Part A
Trial subjects with the first -in-human [FIH] immunization will be immunized using a sentinel
dosing/subject staggering (EMA 2017 guidance “ Strategies to Identify and Mitigate Risks for First -in-
Human and Ea rly Clinical Trials with Investigational Medicinal Products ”). The FIH starting dose and
the planned escalation/de -escalation doses are given in Table 1 of protocol version 8. Dose escalation
rules have been defined in this protocol to guide dose escalatio n.
For all cohorts, if the investigator considers necessary, the planned observation periods before proceeding
to dose further subjects in the same group may be prolonged by 24 h.
Dose de -escalation in the case of possible vaccine -related toxicities wil l be guided by the Safety Review
Committee (SRC), as required.
In Cohort 1, the sentinel dosing/subject staggering process will be as follows:
• One sentinel subject will be dosed on one day.
• If the dosing in this subject was considered to be safe and well tolerated by the investigator after
24±2 h observation on site, 5 further subjects will be dosed (with intervals of at least 1 h between
subjects).
• If the dosing in these 5 subjects was con sidered to be safe and well tolerated by the investigator
based on 48 h data (24±2 h observation on site and phone interview for assessment 48±2 h after
immunization; in addition to the available 48±2 h data from the sentinel subject):
o The remaining 6 su bjects in the group will be dosed (with intervals of at least 30 min
between subjects).
o If approved by the SRC, the next planned escalation dose will be initiated. The data
assessed by the SRC comprises 48 h data for 6 subjects including observation on si te,
short summary of phone interview (including statement about diary reports), vital signs,
investigator reported local and systemic reactions, TEAEs, solicited local & systemic
reactions, blood/clinical laboratory data, and brief physical examination out come.
o If approved by the SRC, the planned de -escalation dose in Cohort 3 will be initiated.
For any subsequent dose -escalation cohorts (to doses higher than the maximum already tested for a
vaccine candidate), the sentinel/subject staggering process will be as follows:
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This document is confidential Page 7 of 73 • Two sentinel subjects will be dosed on one day (with intervals of at least 30 min between
subjects).
• If the dosing in these subjects was considered to be safe and well tolerated by the investigator
after 24±2 h observation on site, 4 fur ther subjects will be dosed (with intervals of at least 30 min
between subjects).
• If the dosing in these 4 subjects was considered to be safe and well tolerated by the investigator
based on 48 h data (24±2 h observation on site and phone interview for as sessment 48±2 h after
immunization; in addition to the available 48 h data from the sentinel subjects):
o The remaining 6 subjects in the group will be dosed (with intervals of at least 30 min
between subjects).
o If approved by the SRC, the next planned es calation dose (see Table 1) will be initiated.
The data assessed by the SRC comprises 48 h data for 6 subjects including observation
on site, short summary of phone interview (including statement about diary reports), vital
signs, investigator reported loc al and systemic reactions, TEAEs, solicited local &
systemic reactions, blood/clinical laboratory data, and brief physical examination
outcome.
The maximum allowed dose for each vaccine candidate is defined in the protocol .
For the planned dose de -escal ation cohorts, 12 subjects may be dosed on one day (with intervals of at
least 30 min between subjects). The doses in these cohorts in younger adults must be lower than doses
than doses that have shown acceptable tolerability in younger adults (based on th e data from 12 subjects
up until 48 h after the first dose). The same dose will not be administered twice, i.e., in two cohorts.
For BNT162b1 and BNT162b2, administration of the planned 10 µg dose in older subjects (Cohort 8)
may start once at least a 30-µg dose has shown acceptable tolerability in younger adults (based on the
data from 12 subjects up until 48 h after the boost dose). The dose in Cohort 8 must also be confirmed by
the SRC. In Cohort 8, 12 subjects will be dosed using a sentinel dosing/subj ect staggering (2 -4-6) process
with intervals of at least 1 h between the first 6 subjects and then at least 30 min intervals for the
remaining 6 subjects.
For BNT162b1 and BNT162b2, administration of the planned dose escalation cohorts in older adults
(Cohorts 9 and 10), 12 subjects will be dosed using a sentinel dosing/subject staggering (2 -4-6) process
with intervals of at least 30 min between subjects. The doses planned in these cohorts will only be
administered if the dose is confirmed by the SRC.
For the unplanned dose de -escalation cohorts, i.e., where the SRC requests the use of a reduced dose for
safety reasons, 12 subjects may be dosed on one day with intervals of at least 30 min between subjects (as
for planned de -escalation cohorts).
Note: B NT162b1 and BNT162b2 are modified uridine RNAs, while BNT162a1 and
BNT162c2 are both nucleoside -modified pseudomethyl -uridine containing RNAs. RNA modification is
known to impact the extent of innate immune activation at a given dose level, and thus poten tially the
extent of reactogenicity. Therefore, tolerability data obtained with one of the vaccine variants of each of
these pairs may be potentially informative for the respective other one and should be taken in
consideration by the SRC for recommendatio ns of lower or interim doses.
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This document is confidential Page 8 of 73 In the case that an individual experiences dose limiting toxicities or that the frequency or pattern of AEs
within a sub -cohort gives cause for concern, the investigator may request by phone an ad hoc review by
the SRC, at any time, before further doses of a given vaccine construct are administered.
Part B
Part B will only be started if approved using a substantial protocol amendment.
Details of Part B will be defined using a protocol amendment after thorough evaluation of
immunogenicity and safety data from Part A for each vaccine candidate individually. Part B may be
initiated for one or more vaccines while Part A is still ongoing, depending on the available data.
Safety data to be evaluated includes the package used by the SRC to assess individual d ose levels and in
addition any other safety observations that may be reported until the data cut off. Immunogenicity of all
doses will be thoroughly assessed.
The protocol amendment will include a summary of relevant safety and tolerability data collecte d in Part
A. This protocol amendment will also include Part B specific inclusion/exclusion criteria,
objectives/endpoints, a description of the planned statistical analyses, and descriptions of any added trial
assessments and procedures.
Part B will use a randomized, placebo -controlled design in the likely target population (e.g., higher risk
populations such as immunocompromised populations). Part B may employ a surrogate marker as a
measure of vaccine efficacy.
2.3 Trial Design Datasets
Are Trial Design d atasets included in the submission? - Yes
Dataset Dataset Label
TA Trial Arms
TE Trial Elements
TV Trial Visits
TI Trial Inclusion/Exclusion Criteria
TS Trial Summary
2.3.1 TA - Trial Arms
Subjects are randomly assigned to receive either BNT162b1 or BNT162b2 .
The detailed information for ARM and ARMCD is shown in the table below.
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BNT162b1 Cohort 01 10 ug BNT162b1 -01-10
BNT162b1 Cohort 02 30 ug BNT162b1 -02-30
BNT162b1 Cohort 03 1 ug BNT162b1 -03-1
BNT162b1 Cohort 04 60 ug BNT162b1 -04-60
BNT162b1 Cohort 05 50 ug BNT162b1 -05-50
BNT162b1 Cohort 06 3 ug BNT162b1 -06-3
BNT162b1 Cohort 07 20 ug BNT162b1 -07-20
BNT162b1 Cohort 08 10 ug BNT162b1 -08-10
BNT162b1 Cohort 09 20 ug BNT162b1 -09-20
BNT162b1 Cohort 10 30 ug BNT162b1 -10-30
BNT162b2 Cohort 01 10 ug BNT162b2 -01-10
BNT162b2 Cohort 02 30 ug BNT162b2 -02-30
BNT162b2 Cohort 03 1 ug BNT162b2 -03-1
BNT162b2 Cohort 05 20 ug BNT162b2 -05-20
BNT162b2 Cohort 06 3 ug BNT162b2 -06-3
BNT162b2 Cohort 08 10 ug BNT162b2 -08-10
BNT162b2 Cohort 09 20 ug BNT162b2 -09-20
BNT162b2 Cohort 10 30 ug BNT162b2 -10-30
2.3.2 TE - Trial Elements
There are 27 Elements. SCRN refers to Screening Element ; PREDOSE refers to Pre-dose
assessments Element ; FUP represents the safety follow up Element ; and VXB1C1P,
VXB1C1B, VXB1C2P, VXB1C2B, VXB1C3P, VXB1C3B, VXB1C4P, VXB1C4B,
VXB1C5P, VXB1C5B, VXB1C6P , VXB1C6B, VXB1C7P, VXB1C7B, VXB1C8P,
VXB1C8B, VXB1C9P, VXB1C9B, VXB1C10P, VXB1C10B, VXB2C1P, VXB2C1B
VXB2C2P, VXB2C2B, VXB2C3P, VXB2C3B, VXB2C5P, VXB2C5B, VXB2C6P,
VXB2C6B, VXB2C8P, VXB2C8B, VXB2C9P, VXB2C9B, VXB2C10P, VXB2C10B
represent Treatment Element s.
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The trial visits dataset describes the planned visits of the trial and consists of 12 visits. Each visit
and visit description are shown in the table below.
VISITNUM VISIT VISITDY Description
1 Visit 0 (Day -30 to 0) Informed consent and Screening
begin up to 0 to 30 days prior to
dosing
2 Visit 1 (Day 1) 1 Baseline records and vaccination
administration (Day 1)
3 Visit 2 (Day 2) 2 22 to 26 hours from first vaccination
4 Phone Call (48 h) 46 to 50 hours after visit 1
5 Visit 3 (Day 8) 8 7 to 9 days after visit 1
6 Visit 4 / Dosing (Day 22) 22 20 to 24 days after visit 1
6.1 Phone Call (48 h after Day
22) 46 to 50 hours after visit 4
7 Visit 5 (Day 29) 29 7 days after visit 4
8 Visit 6 (Day 43) 43 21 days after visit 4
9 Visit 7 / EoT Visit (Day 50) 50 Start of end of treatment visit (28
days after visit 4)
10 Visit 8 / FU Visit (Day 85) 85 Follow -up visit (63 days after visit
4)
11 Visit 9 / FU Visit (Day
184) 184 Follow -up visit (162 days after visit
4)
2.3.4 TI - Trial Inclusion/Exclusion Criteria
See Appendix I for complete Inclusion/Exclusion criteria. Criteria in TI have been shortened to a
length of 200 from protocol text. Criteria with the text ‘_1’ appended correspond to original
protocol criteria which were later amended in version 2.0, prior to the firs t collection of data in
the CRF. Criteria with a letter appended ( e.g. ‘EX24A’) correspond to original protocol criteria
which were later removed in version 2.0. If the criterion changed in meaning or was inserted from
one version of the protocol to th e next, additional observations with the corresponding
IETESTCD are created in TI. The variable TIVERS indicates the version of the protocol to which
the criterion belongs.
2.3.5 TS - Trial Summary
The Trial Summary (TS) dataset details a summary of the trial in a structured format. Each record
in the Trial Summary dataset contains the value of a parameter, a characteristic of the trial. Trial
Summary was used to record basic information about the study such as trial phase, protocol title,
and trial objectives, as well as, information about the planned and actual trial characteristics.
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3. Subject Data Description
3.1 Overview
The CSR data is based on the ongoing study. The study SDTMs are based on fina l database and represent
all data collected for a subject across the study visits. Datasets include data that were collected on case
report forms (CRFs) and were sourced as eDT. The collected data were transformed to SDTM conformed
standards by following the SDTM IG v3.2 and were verified using the Pinnacle 21 Enterprise 4.1.4 tool.
The SDTM datasets were utilized to generate the study ADaM datasets per ADaM IG 1.0.
Are the submitted data taken from an ongoing study? Yes
If yes, describe the data cut or database status:
Data cutoff date of 23Oct 2020 is applied by comparing XXDTC or XXSTDC from respective
SDTM domains. Apart from data cutoff this esub is limited to cohorts described in the section
2.3.1
Were the SDTM datasets used as sources for the analysis datasets? Yes
Do the submission datasets include screen failures? No
Were any domains planned, but not submitted because no data were collected? Yes
Dataset Dataset Label
IE Inclusion/Exclusion Criteria Not Met
DD Death Details
Are the submitted data a subset of collected data? No
3.2 Traceability Flow Diagram
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This document is confidential Page 12 of 73 3.3 Annotated CRFs
Collected fields and pages that have not been tabulated have been annotated as "Not Submitted".
BioNTech SE collects certain data elements to facilitate operational processes including data cleaning
and dynamically creating additional forms in the electronic data capture system. All fields and pages
that have been annotated as "Not Submitted" meet this criterion.
Explanation of data fields [Not Submitted]
aCRF page
Number (s) Data Collection Field Explanation of why [NOT SUBMITTED]
1 Was the subject re -screened ? Not needed for analysis.
3 BMI (calculated) (kg/m² ) BMI is derived in VS dataset .
4 Childbearing potential= N/A Not needed for analysis.
5,24 Specimen =N/A Not needed for analysis.
6,15 /Abnormal/ND and Finding
(calculated) Abnormal results are captured in PEORRES
values and N/D and Findings(calculated) is not
needed for analysis.
14 Subject meets all inclusion
criteria and does not meet any
exclusion criteria Not needed for analysis.
19 Entire page: Blood sample for
CMI Not needed for analysis.
20 Scheduled time Not needed for analysis.
22,23 ,29,31,33 Test Name Not needed for analysis.
24 Phone call visit N/A Phone call visits valid only for first 6 subjects
per cohort and rest will be N/A which is not
used for analysis
25 Trial fully completed =No Not needed for analysis.
27 Any Medical History ? Yes/ No Not needed for analysis.
34 Any Adverse Events ? Yes/No Not needed for analysis.
34,36 Start Time unkn. Not needed for analysis.
34,36 End Time unkn. Not needed for analysis.
34,36 Ongoing =No Not needed for analysis.
36 Any prior/concomitant
medication/therapy? Not needed for analysis.
37 Any Comments ? Yes/No Not needed for analysis.
38 Any Protocol Deviations?
Yes/No
Not needed for analysis.
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Number (s) Data Collection Field Explanation of why [NOT SUBMITTED]
39,41 Specimen Not needed for analysis.
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This document is confidential Page 14 of 73 3.4 SDTM Subject Domains
Dataset - Dataset Label Efficacy Safety Other Custom SUPP -
- Related Using
RELREC
AE - Adverse Events X X
CE - Clinical Events X FACE VS
CM - Concomitant/Prior
Medications X X
CO - Comments X
DM - Demographics X X
DS - Disposition X X
DV - Protocol Deviations X
EC - Exposure as Collected X X
EG - ECG Test Results X
EX - Exposure X X
FACE - Findings About
Clinical Events X X
IS - Immunogenicity
Specimen Assessments X
LB - Laboratory Test
Results X X
MB - Microbiology
Specimen X
MH - Medical History X
PE - Physical Examination X X
RP - Reproductive System
Findings X X
SE - Subject Elements X
SV - Subject Visits X
VS - Vital Signs X X CE
XA - Ancillary Analysis
and Visit Details X X
XB - HLA Typing X
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3.4.1 AE - Adverse Events
Adverse Events domain consists of one record per adverse event, per subject. The entry of a “Y”
for the serious adverse event variable, AESER, indicates the AE meets the criteria as serious per
investigator report and the definition in the CRF guidance. The following additi onal collected
data are in supplemental qualifier.
QNAM Description
AEEPRELI Epi/Pandemic Related Indicator
AETRTEM Treatment Emergent Flag
AE_DLT Dose limiting Toxicity
3.4.2 CE - Clinical Events
Clinical Events domain consists of one recor d per reaction per observation period per subject .
Following the “flat model” described in the Therapeutic Area Data Standards User Guide for
Vaccines, daily diary records are recorded in the FACE and VS domains and summarized in a
global event recor d (one each for the observation period following the prime/boost vaccinations
administered), whether or not a reactogenicity event occurred during the assessment interval.
While FACE contains records for reaction assessments provided by both the investiga tor and the
study subject (variable FAEVAL), only the study subject assessments (from the subject’s diary)
are used in the generation of the CE domain. Likewise, only the temperature records in the VS
domain which were obtained from the diary data (VSCAT = ‘REACTOGENICITY’) are used for
generating CE.
3.4.3 CM - Concomitant/Prior Medications
Concomitant Medications domain consists of one record per recorded medication occurrence
or constant -dosing interval, per subject. The following additional collected data are in
supplemental qualifier.
QNAM Description
AE_NO1 Corresponding AE No 1
AE_NO2 Corresponding AE No 2
AE_NO3 Corresponding AE No 3
CMATC1 ATC Level 1 Description
CMATC1CD ATC Level 1 Code
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CMATC2 ATC Level 2 Description
CMATC2CD ATC Level 2 Code
CMATC3 ATC Level 3 Description
CMATC3CD ATC Level 3 Code
CMATC4 ATC Level 4 Description
CMATC4CD ATC Level 4 Code
O_FREQ Other frequency, specify
O_ROUTE Other route, specify
O_UNIT Other unit, specify
3.4.5 DM - Demographics
Demographics domain consists of one record per subject. The following additional collected data
are in supplemental qualifier.
QNAM Description
AGE_M Add. months to Age in years (months)
3.4.6 DS - Disposition
Disposition domain consists of one record per disposition status or protocol milestone, per
subject. The following additional collected data are in supplemental qualifier.
QNAM Description
COHORT Subject is allocated to Cohort
DSEPRELI Epi/Pandemic Related Indicator
GROUP Subject is allocated to Group
LASTCONT Date of last visit/contact
PREV_TSN Previous TSNs
PROTVERS Protocol Version
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This document is confidential Page 17 of 73 3.4.7 DV - Protocol Deviations
Protocol Deviations domain consists of one record per protocol deviation per subject . The
following additional collected data are in supplemental qualifier.
QNAM Description
DVREAS Reason for Deviation
3.4.8 EC - Exposure as Collected
Exposure as Collected domain consists of one record per protocol -specified study treatment,
collected -dosing interval, per subject. The following additional collected data are in supplemental
qualifier.
QNAM Description
ADMNPPSP Adm. not acco rding to Protocol, specify
ADMPPROT Administration according to protocol?
ECEPADJI Epi/Pandemic Related Adjustment Reas Ind
ECREASOC Reason for Occur Value
MED_NO Medication Number
TOTDOS Total Dose given?
3.4.9 EG - ECG Test Results
ECG Test Results domain consists of o ne record per ECG observation per time point per visit per
subject . CRF collected significant findings results are kept under supplement qualifier domain.
The following additional collected data are in supplemental qualifier.
QNAM Description
CODE Code of ECG Finding
EGCLSIG Clinically Significant
3.4.10 EX - Exposure
Exposure domain consists of one record per constant dosing interval, per subject. The Exposure
domain collected the details of a subject's exposure to protocol -specified study treatment as
mentioned in TA section. The following additional collected data are in supplemental qu alifier.
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This document is confidential Page 18 of 73 QNAM Description
ADMNPPSP Adm. not according to Protocol, specify
ADMPPROT Administration according to protocol?
EXEPADJI Epi/Pandemic Related Adjustment Reas Ind
EXEPINTI Epi/Pandemic Related Interrupt Reas Ind
MED_NO Medication Number
TOTDOS Total Dose given?
3.4.11 FACE - Findings About Clinical Events
Findings About Clinical Events domain consist s of one record per finding (occurrence / severity)
per object (reactogenicity event) per reference time point (boost / prime vaccination) per time
point (date/time of assessment) per evaluator (investigator / study subject) per subject . Each
assessment of a reactogenicity event, whether provided by the investigator or recorded by the
subject in a diary, are recorded in this domain and are then summarized (in conjunction with
temperature data from the VS domain) in the “flat model” CE domain. The following additional
collected data are in supplemental qualifier.
QNAM Description
STUDYDAY Reported Study Day of Collection
3.4.12 IS - Immunogenicity Specimen Assessments
Immunogenicity Specimen Assessment s domain consists of one record per immunogenicity test
per visit per subject. The IS domain collected the result based upon blood samples for
immunogenicity presented under ISCAT=’IMMUNOGENICITY’ only. If no measurements were
assessed for the entire visit, a record exists where ISTESTCD =” ISALL” and ISSTAT =” NOT
DONE”. QNS is Quantity Not Sufficient and has been treated as Not Done. LLOQs to define
BLQ as below:
RBD IgG dLIA (COV19_RBD_IGG_LXA): 1.1505 U/mL
S1 IgG dLIA (COV19_S1_IGG_LXA): 1.2665 U/mL
Neutralization 50% (COV2_MNG_SERUM_NT50): 20, (negative s assigned titer of 10)
Neutralization 90% (COV2_MNG_SERUM_NT90): 20, (negatives assigned titer of 10)
3.4.13 LB - Laboratory Test Results
Laboratory Test Results domain consists of one record per analyte per planned time point number
per time point reference per visit per subject. Reference range was not applied to the chemistry
analyte (LBCAT=CHEMISTRY) 'Follicle Stimulating Hormone' or to the following
hematology analytes (LBCAT=HEMATOLOGY) when performed via Microscopy on Blood
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This document is confidential Page 19 of 73 Smears (LBMETHO D=MICROSCOPY and LBSPEC=BLOOD SMEAR): Basophils,
Eosinophils, Lymphocytes, Lymphocytes Atypical/Leukocytes, Monocytes, Neutrophils, Smudge
Cells/Leukocytes. The following additional collected data are in supplemental qualifier.
QNAM Description
LBCLSIG Clinically Significant
LBLOINC1 LOINC Code for Identification
LBLOINC2 LOINC Code for second Identification
LBORRES1 Identification for Result
LBORRES2 Second Identification for Result
RBB Report Blood Count
RBB2 Report Blood Count 2
3.4.14 MB - Microbiology Specimen
Microbiology Specimen domain consists of one record per microbiology specimen finding per
time point per visit per subject .
3.4.15 MH - Medical History
Medical History domain consist s of one record per medical history event, per subject.
3.4.16 PE - Physical Examination
Physical Examination domain consists of one record per body system or abnormality, per visit,
per subject. The following additional collected data are in supplemental qualifier.
QNAM Description
PECLSIG Clinically Significant
3.4.17 RP - Reproductive System Findings
Reproductive System Findings domain consists of o ne record per Reproductive System Finding
per time point per visit per subject .The following additional collected data are in supplemental
qualifier.
QNAM Description
OTH_SPEC Specification for Other Reason
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This document is confidential Page 20 of 73 3.4.18 SE - Subject Elements
Subject Element domain consists of one record per actual element per subject.
3.4.19 SV - Subject Visits
Subject Visits domain consists of one record per actual visit per subject.
3.4.20 VS - Vital Signs
Vital Signs dataset consists of one record per vital sign measurem ent, per time point, per subject.
To implement flat model, temperature records from subject diary data are mapped to the VS
domain with VSCAT=REACTOGENICITY. If measurements were not collected for VSCAT=
‘REACTOGENICITY ’, a record exists with VSORRES=’’ and VSSTAT =’NOT DONE ’. The
following additional collected data are in supplemental qualifier.
QNAM Description
STUDYDAY Reported Study Day of Collection
VSCLSIG Clinically Significant
3.4.21 XA - Ancillary Analysis and Visit Details
Ancillary Analysis and Visit Details dataset consists of o ne record per finding per time point per
visit per subject . The following additional collected data are in supplemental qualifier.
QNAM Description
ACT_TPT Actual observation period (hours)
REASON Reason
RES BS Blood Sampling for Research Purposes
3.4.2 2 XB - HLA Typing
HLA Typing dataset consists of o ne record per finding per time point per subject .
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This document is confidential Page 21 of 73 4. Data Conformance Summary
4.1 Conformance Inputs
Was a validator used to evaluate conformance ? Yes
If yes, speci fy the version(s) of the validation rules : Pinnacle 21
Enterprise version 4.1.4
Validation
Engine version 1907.1
Were sponsor -defined validation rules used to evaluate conformance? No
If yes, describe any significant sponsor -defined validation rules: n/a
Were the SDTM datasets evalu ated in relation to define.xml? Yes
Was define.x ml evaluated ? Yes
Provide any additional compliance evaluation information :
4.2 Issues Summary
Check ID Diagnostic
Message FDA
Severity Dataset Count
(Issue Rate) Explanation
CT2002 CMDOSU
value not
found in
'Unit'
extensible
codelist Warning CM 8 (2.18%) Reported as collected; Term
similar to 'OTHER' is not
present in codelist, and
codelist is extensible.
CT2002 CMROUTE
value not
found in
'Route of
Administrati
on Response'
extensible
codelist Warning CM 1 (0.27%) Reported as collected; Term
similar to 'OTHER' is not
present in codelist, and
codelist is extensible.
CT2002 CMDOSFRQ
value not
found in
'Frequency'
extensible
codelist Warning CM 8 (2.18%) Reported as collected; Terms
similar to 'OTHER' and 'NOT
APPLICABLE' are not
present in codelist, and
codelist is extensible.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
CT2002 COEVAL
value not
found in
'Evaluator'
extensible
codelist Warning CO 147
(35.94%) Reported as collected; Term
similar to 'LABORATORY'
is not present in codelist, and
codelist is extensible.
CT2002 ISORRESU
value not
found in
'Unit'
extensible
codelist Warning IS 1418
(49.20%) Codelist is extensible,
additional value 'NA' has
been added for ISORRESU.
CT2002 ISSTRESU
value not
found in
'Unit'
extensible
codelist Warning IS 1418
(49.20%) Codelist is extensible,
additional value 'NA' has
been added for ISSTRESU.
CT2002 LBSPEC
value not
found in
'Specimen
Type'
extensible
codelist Warning LB 275 (0.45%) Codelist is extensible,
additional value 'BLOOD
SMEAR' has been added for
LBSPEC.
CT2002 RPTESTCD
value not
found in
'Reproductiv
e System
Findings Test
Code'
extensible
codelist Warning RP 75 (31.25%) RPTESTCD values to
represent 'Reason for Non-
childbearing potential'
(NON_REAS) and 'Date of
Sterilization' (STER_DTC)
are not present in codelist,
and codelist is extensible.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
CT2002 RPTEST
value not
found in
'Reproductiv
e System
Findings Test
Name'
extensible
codelist Warning RP 75 (31.25%) RPTEST values similar to
'Reason for Non -childbearing
potential' and 'Date of
Sterilization' are not present
in codelist, and codelist is
extensible.
CT2002 QEVAL
value not
found in
'Evaluator'
extensible
codelist Warning SUPPC
M 2924
(91.72%) Reported as col lected. Value
similar to 'MEDICAL
CODER' is not present in
codelist, and codelist is
extensible.
SD0006 No baseline
flag record in
MB for
subject Warning DM 37 (17.13%) For the subjects triggering
this issue, records present in
the MB domain contain only
categorical results (e.g.
Negative) for which a
baseline flag is not
applicable.
SD0021 Missing End
Time -Point
value Warning AE 5 (0.85%) Reported as collected; Study
is ongoing.
SD0021 Missing End
Time -Point
value Warning CE 2 (< 0.1%) Reported as collected; Study
is ongoing.
SD0021 Missing End
Time -Point
value Warning CM 41 (11.17%) Reported as collected; Study
is ongoing.
SD0022 Missing Start
Time -Point
value Warning CE 2 (< 0.1%) Reported as collected; Study
is ongoing.
SD0022 Missing Start
Time -Point
value Warning MH 2 (2.63%) Start date was not entered.
Data provided as collected.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
SD0026 Missing
value for
RPORRESU,
when
RPORRES is
provided Warning RP 48
(100.00%) A unit is not applicable when
RPORRES value is a date.
SD0029 Missing
value for
RPSTRESU,
when
RPSTRESC
is provided Warning RP 48
(100.00%) A unit is not applicable when
RPSTRESC value is a date.
SD0031 Missing
values for
MHSTDTC,
MHSTRF
and
MHSTRTPT,
when
MHENDTC,
MHENRF or
MHENRTPT
is provided Warning MH 2 (2.63%) Start date was not entered.
Data provided as collected.
SD0047 Missing
value for
FAORRES,
when
FASTAT or
FADRVFL is
not populated Warning FA 152
(66.09%) Result was not entered. Data
provided as collected.
SD0047 Missing
value for
MBORRES,
when
MBSTAT or
MBDRVFL
is not
populated Warning MB 5 (100.00%) Result was not entered. Data
provided as collected.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
SD0080 AE start date
is after the
latest
Disposition
date Error AE 29 (4.93%) Reported as collected; Study
is ongoing.
SD0082 Exposure end
date is after
the latest
Disposition
date Warning EX 43 (10.39%) Study is ongoing.
SD0088 RFENDTC is
not provided
for a
randomized
subject Warning DM 36 (16.67%) Study is ongoing.
SD1076 Model
permissible
variable
added into
standard
domain Notice CE 17 (43.59%) Variables CEHLTCD,
CEPTCD, CETPTREF,
CEHLT, CEHLGTCD,
CEEVINTX, CELNKGRP,
CESOC, CETPT, CELLT,
CEHLGT, CEBDSYCD,
CERFTDTC, CELLTCD,
CETPTNUM, CESOCCD,
CEDUR added to provide
complete information
regarding collected data and
to provide relationship
information between CE, VS,
and FACE domains.
SD1076 Model
permissible
variable
added into
standard
domain Notice CO 1 (4.00%) Variable COVAL1 added to
accommodate text l onger than
200 characters for COVAL.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
SD1076 Model
permissible
variable
added into
standard
domain Notice EC 2 (9.09%) Variables VISITNUM and
VISIT added to provide
complete information
regarding collected data.
SD1076 Model
permissible
variable
added into
standard
domain Notice EX 2 (6.90%) Variables VISITNUM and
VISIT added to provide
complete information
regarding collected data.
SD1076 Model
permissible
variable
added into
standard
domain Notice FA 8 (15.09%) Variables FARFTDTC,
FAEVLINT, FALNKGRP,
FATPT, FATPTREF,
FALNKID, FAEVINTX,
FATPTNUM added to
provide complete information
regarding collected data and
to provide relationship
information between CE and
FACE domains.
SD1076 Model
permissible
variable
added into
standard
doma in Notice MB 5 (12.50%) Variables MBORNRHI,
MBSTNRC, MBNRIND,
MBTSTDTL, MBSTNRHI
added to provide complete
information regarding data
provided by vendor
laboratory.
SD1076 Model
permissible
variable
added into
standard
domain Notice MH 10 (23.81%) Variables MHHLGTCD,
MHLLT, MHSOCCD,
MHHLTCD, MHPTCD,
MHHLGT, MHLLTCD,
MHBDSYCD, MHSOC,
MHHLT added to provide
complete information
regarding collected data.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
SD1076 Model
permissible
variable
added into
standard
domain Notice TS 2 (20.00%) Variable TSVAL1 , TSVAL2
added to accommodate text
longer than 200 characters for
TSVAL.
SD1076 Model
permissible
variable
added into
standard
domain Notice VS 2 (4.55%) Variables VSLNKID and
VSLNKGRP added to
provide relationship
information between the CE
and VS domains .
SD1078 Permissible
variable with
missing
value for all
records Notice AE 5 (29.41%) Fields on the acrf are
annotated to these variables
(AESDISAB, AESLIFE,
AESCONG, AESMIE,
AESDTH), but no
information has been entered
into these fields to date.
SD1078 Permissible
variable with
missing
value for all
records Notice CM 2 (14.29%) Fields on the acrf are
annotated to these variables
(CMENTPT and
CMENRTPT), but no
information has been entered
into these fields to date.
SD1078 Permissible
variable with
missing
value for all
records Notice EG 2 (18.18%) Fields on the acrf are
annotated to these variables
(EGSTAT and EGREASND),
but no information has been
entered into these fields to
date.
SD1078 Permissible
variable with
missing
value for all
records Notice IS 1 (10.00%) ISMETHOD provided with
vendor data, but not current ly
populated. Study is ongoing.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
SD1078 Permissible
variable with
missing
value for all
records Notice LB 2 (16.67%) Fields on the acrf are
annotated to these variables
(LBSTAT and LBREASND),
but no information has been
entered into these fields to
date.
SD1078 Permissible
variable with
missing
value for all
records Notice MB 2 (14.29%) Fields on the acrf are
annotated to these variables
(MBSTAT and
MBREASND), but no
information has been entered
into these fields to date.
SD1117 Duplicate
records Warning FA 2 (< 0.1%) FACE contains similar
records for "NOT DONE"
reports of data collection.
When using the Key
Variables provided in the
define, records are unique.
SD1122 Missing
value for
RPSTRESN Warning RP 48
(100.00%) RPSTRESC represents a date
and should therefore not be
reported as a numeric value.
SD1201 Duplicate
records in
AE domain Warning AE 1 (0.17%) The record triggering thi s
issue was mapped to two
MedDRA Lower -Level
Terms. When using the Key
Variables provided in the
define, records are unique.
SD1201 Duplicate
records in CE
domain Warning CE 1889
(30.42%) CE contains similar records
for each of the two dosing
periods (identified by dosing
date/time variable
CERFTDTC). When using
the Key Variables provided in
the define, records are unique.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
SD1201 Duplicate
records in
DV domain Warning DV 23 (11.27%) The sa me deviation is
recorded for multiple
assessments on the same date.
DVSEQ provides uniqueness
in this domain.
SD1203 CODTC date
is after
RFPENDTC Error CO 3 (23.08%) Reported as collected;
Comment regarding subject
provided after subject's
participation in trial was
complete.
SD1229 MBORRES
value is null
when
MBTESTCD
=
'SARSCOV2' Error MB 5 (2.02%) Result was not entered. Data
provided as collected.
SD1272 PETESTCD
equals
'OTHER' Warning PE 2 (< 0.1%) Reported as captured on CRF.
Provides best representation
of collected data.
SD1290 Multiple
disposition
events for the
same
EPOCH Error DS 1 (0.54%) Subject BNT162 -01-276-02-
0183 completed treatment
(was administered both
vaccines) but discontinued
before completing FOLLOW -
UP epoch.
SD1312 TSVAL is
missing for
the PCLAS
Trial
Summary
Parameter,
when STYPE
parameter
equals
'INTERVEN
TIONAL' Error TS 1 (100.00%) Study involves novel
treatments which are not
registered in FDA Substance
Registration System (SRS).
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
SD1319 DSSTDTC is
before
RFICDTC Error DS 18 (1.76%) For the subjects triggering
this issue, rescreening
occurred and RFICDTC is set
to the date of informed
consent which was signed at
final screening.
SD1320 Missing
value for
FASTRESC,
when
FASTAT is
null Warning FA 152 (0.11%) Reported as collected; Study
is ongoing.
SD1320 Missing
value for
MBSTRESC,
when
MBSTAT is
null Warning MB 5 (0.34%) Result was not entered. Data
provided as collected.
SD1339 Missing
EPOCH
value, when
a start or
observation
date is
provided Warning CM 3 (0.89%) Medications were started
prior to the patient's
SCREENING epoch and are
therefore not assigned an
EPOCH value.
SD1344 Value for
CMDECOD
not found in
WHODrug
dictionary Error CM 1 (0.27%) Due to ongoing Study,
mapping for
CMDECOD=ETHINYLEST
RADIOL;ETONOGESTREL
ETHINYLESTRADIOL;ETO
NOGESTREL for
USUBJID=BNT162 -01-276-
02-0177 was not aligned with
dictionary at the time of data
cut.
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Message FDA
Severity Dataset Count
(Issue Rate) Explanation
SD2260 Invalid
TSVAL
value for
TRT Error TS 2 (100.00%) Study i nvolves novel
treatments which are not
registered in FDA Substance
Registration System (SRS).
SD2261 Invalid
TSVALCD
value for
TRT Error TS 2 (100.00%) Study involves novel
treatments which are not
registered in FDA Substance
Registration System (SRS).
TS0050 Missing PC
dataset Warning GLOBA
L 1 (100.00%) Pharmacokinetic data is not
captured in this protocol.
TS0051 Missing PP
dataset Warning GLOBA
L 1 (100.00%) Pharmacokinetic data is not
captured in this protocol.
TS0057 LBSTRESN
is populated
but
LBSTNRHI
is not
populated Warning LB 213 (0.51%) A reference range was not
applied to the chemistry
analyte
(LBCAT=CHEMISTRY)
'Follicle Stimulating
Hormone' or to the following
hematology analytes
(LBCAT=HEMATOLOGY)
when performed via
Microscopy on Blood Smears
(LBMETHOD=MICROSCO
PY and LBSPEC=BLOOD
SMEAR): Basophils,
Eosinophils, Lymphocytes,
Lymphocytes
Atypical/Leukocytes,
Monocytes, Neutrophils,
Smudge Cells/Leukocytes.
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Severity Dataset Count
(Issue Rate) Explanation
DD0050 Domain/SAS
DatasetName
mismatch for
split dataset Error DEFI N
E 1 (100.00%) The "flat model" described in
the Vaccines Therapeutic
Area User Guide has been
utilized for reactogenicity
data in this study. To clearly
indicate that the data
contained in the "Findings
About" domain is wholly that
of reactogenicity findi ngs,
sponsor has chosen to utilize
the names FACE and
SUPPFACE, even though
there is no split of the FA /
SUPPFA domains.
DD0116 FATESTCD/
FATEST
mismatch in
Codelist
'Vaccines
Findings
About Test
Code' Notice DEFIN
E 1 (100.00%) While the FATESTCD =
'OCCUR' records do provide
findings related to the
CEOCCUR qualifier variable,
the use of FATEST =
'Occurrence' is not aligned
with the Vaccines Finding
About Test Name (VNFATS)
Controlled Terminology
which has been applied to the
FATEST variable.
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This document is confidential Page 33 of 73 Appendix I: Inclusion/Exclusion Criteria
Protocol/
Amendment
Version Category IETESTCD Full Text of Criterion
1.0 Inclusion IN01 Have given informed consent by signing the ICF before
initiation of any trial -specific procedures.
1.0 Inclusion IN02_1 They must be willing and able to comply with scheduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions, and other requirements of the trial.
1.0 Inclusion IN03 They must be able to understand and follow trial -related
instructions.
1.0 Inclusion IN04_1 They must be aged 18 ≤ 55 years and weigh at least 50 kg
at Visit 0.
1.0 Inclusion IN05 They must be healthy based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and urine chemistry) at Visit 0.
1.0 Inclusion IN06 Women of ch ildbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin in urine at
Visit 0 and Visit 1. Women that are postmenopausal or
permanently sterilized will be considered as not having
reproductive potential.
1.0 Inclusion IN07 WOCBP must agree to practice one highly effective form
of contraception during the trial, starting after Visit 0 and
continuously until 60 d after receiving the last
immunization.
1.0 Inclusion IN09 WOCBP must agree not to donate eggs (ova, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving the
last immunization.
1.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partner of
childbearing potential during the trial, starting after Visit 0
and continuously until 60 d after receiving the last
immunization.
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1.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
1.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visit 0.
1.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Visit 0 and continuously until 28 d after
receiving the last immunization.
1.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the residual
symptoms will not comp romise their well -being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confound the protocol -specified
assessments.
1.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial , starting after Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
1.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intolerance to
the planned IMP including any excipients of the IMP.
1.0 Exclusion EX04 Had any medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years, which
in the opinion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could preve nt, limit, or confound the protocol -specified
assessments.
1.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuously until at least 90 d after receiving
the last immunization.
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1.0 Exclusion EX06 Had any chronic use (more than 14 continuous days) of any
systemic medications, including immunosuppressant or
other immune -modifying drugs, within the 6 months prior
to Visit 0 unless in the opinion of the investigator, the
medication would not prevent, limit, or confound the
protocol -specified assessments or could compromise
subject safety.
1.0 Exclusion EX07 Received any vaccination within the 28 d prior to Visit 0.
1.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
1.0 Exclusion EX09 Had administration of another investigational product
including vaccines within 60 d or 5 half -lives (whichever is
longer), prior to Visit 0.
1.0 Exclusion EX10_1 Have a known history or a positive test of any of the
following: HIV 1 or 2, Hepatitis B, Hepatitis C.
1.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepines, barbiturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) result at Visit 0 or Visit 1.
1.0 Exclusion EX13 Have a positive breath alcohol test at Visit 0 or Visit 1.
1.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles.
1.0 Exclusion EX15 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
1.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or depende nt person, such as an
employee or student of the trial site).
1.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psychological, or social conditions,
which in the opinion of the investigator, could compromise
their well -being if they participate as trial subjects in the
trial, or that could prevent, limit, or confound the protocol -
specified assessments.
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1.0 Exclusion EX18 Have a history of hypersensitivity or serious reactions to
previous vaccinations.
1.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a previous vaccination.
1.0 Exclusion EX20 Have a history of narcolepsy.
1.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
1.0 Exclusion EX22 Have a history of or suspected immunosuppressive
condition, acquired or congenital, as determined by medical
history and/or physical examination at Visit 0.
1.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability to observe local reactions at the injection site.
1.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or blood products or injury, with in the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunization.
1.0 Exclusion EX24A They were in any country with a high SARS -CoV-2
infection risk (as defined by the RKI at the time Visit 0)
within the 14 d prior to Visit 0.
1.0 Exclusion EX24B They plan to visit any country with a high SARS -CoV-2
infection risk (as defined by the RKI at the time Visit 0),
from Visit 0 until 14 d a fter receiving the last
immunization.
1.0 Exclusion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
1.0 Exclusion EX25A (Once commercially available in Germany) Have a positive
test for anti -SARS -CoV-2 antibodies.
1.0 Exclusion EX26 Have had contact with persons tested positive for SARS -
CoV-2 antibodies within the 30 d prior to Visit 0.
1.0 Exclusion EX27_1 Are vulnerable persons, i.e., soldiers, subjects in detention,
CRO or sponso r staff or their family members.
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2.0 Inclusion IN01 Have given informed consent by signing the ICF before
initiation of any trial -specific procedures.
2.0 Inclusion IN02 They must be willing and able to comply with scheduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions (e.g., to practice social distancing and to follow
good practices to reduce their chances of being infected or
spreading COVID -19), and other requirements of the trial.
2.0 Inclusion IN03 They must be abl e to understand and follow trial -related
instructions.
2.0 Inclusion IN04 They must be aged from 18 to 55 years, have a body mass
index of over 19 kg/m2 and under 30 kg/m2, and weigh at
least 50 kg at Visit 0.
2.0 Inclusion IN05 They must be healthy based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and urine chemistry) at Visit 0.
2.0 Inclusion IN06 Women of childbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin in urine at
Visit 0 and Visit 1. Women that are postmenopausal or
permanently sterilized will be considered as not having
reproductive pot ential.
2.0 Inclusion IN07 WOCBP must agree to practice one highly effective form
of contraception during the trial, starting after Visit 0 and
continuously until 60 d after receiving the last
immunization.
2.0 Inclusion IN08 WOCBP must confirm that they practiced one highly
effective form of contraception for the 14 d prior to Visit 0.
2.0 Inclusion IN09 WOCBP must agree not to donate eggs (ova, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving the
last immunization.
090177e19673667b\Final\Final On: 08-Mar-2021 02:02 (GMT)
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2.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partner of
childbearing potential during the trial, starting after Visit 0
and continuously until 60 d after receiving the last
immunization.
2.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
2.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visit 0.
2.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Visit 0 and continuously until 28 d after
receiving the last immunization.
2.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the residual
symptoms will not compromise their well -being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confound the pr otocol -specified
assessments.
2.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial, starting after Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
2.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intolerance to
the planned IMP including any excipients of the IMP.
2.0 Exclusion EX04 Had any medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years, which
in the opi nion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could prevent, limit, or confound the protocol -specified
assessments.
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2.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuously until at least 90 d after receiving
the last immunization.
2.0 Exclusion EX06 Had any chronic use (more than 14 continuous days) of any
systemic medications, including immunosuppressant or
other immune -modify ing drugs, within the 6 months prior
to Visit 0 unless in the opinion of the investigator, the
medication would not prevent, limit, or confound the
protocol -specified assessments or could compromise
subject safety.
2.0 Exclusion EX07 Received any vaccinat ion within the 28 d prior to Visit 0.
2.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
2.0 Exclusion EX09 Had administration of another investigational product
including vaccines within 60 d or 5 half -lives (whichever is
longer), prior to Visit 0.
2.0 Exclusion EX10 Have a known history or a positive test of any of HIV 1 or
2, Hepatitis B, or Hepatitis C, within the 30 d prior to Visit
0.
2.0 Exclusion EX11 Have a positive PCR -based test for anti -SARS -CoV-2
within the 30 d prior to Visit 0.
2.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepines, barbiturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) result at Visit 0 or Visit 1.
2.0 Exclusion EX13 Have a positive breath alcohol test at Visit 0 or Visit 1.
2.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles .
2.0 Exclusion EX15 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
2.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or dependent person, such as an
employee or student of the trial site).
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2.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psychological, or social conditions,
which in the opinion of the investig ator, could compromise
their well -being if they participate as trial subjects in the
trial, or that could prevent, limit, or confound the protocol -
specified assessments.
2.0 Exclusion EX18 Have a history of hypersensitivity or serious reactions to
previou s vaccinations.
2.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a previous vaccination.
2.0 Exclusion EX20 Have a history of narcolepsy.
2.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
2.0 Exclusion EX22 Have a history of or suspected immunosuppressive
condition, acquired or congenital, as determined by medical
history and/or physical examination at Visit 0.
2.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability to observe local reactions at the injection site.
2.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or blood products o r injury, within the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunization.
2.0 Exclusion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
2.0 Exclusion EX26 Have had contact with persons tested positive for SARS -
CoV-2 antibodies within the 30 d prior to Visit 0.
2.0 Exclusion EX27 Are soldiers, subjects in detention, CRO or sponsor staff or
their family members.
3.0 Inclusion IN01_3 Have given informed consent by signing the informed
consent form (ICF) before initiation of any trial -specific
procedures.
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3.0 Inclusion IN02 They must be willing and able to comply with scheduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions (e.g., to practice social distancing and to follow
good practices to reduce their chances of being infected or
spreading COVID -19), and o ther requirements of the trial.
3.0 Inclusion IN03 They must be able to understand and follow trial -related
instructions.
3.0 Inclusion IN04 They must be aged from 18 to 55 years, have a body mass
index over 19 kg/m2 and under 30 kg/m2, and weigh at
least 50 kg at Visit 0.
3.0 Inclusion IN05 They must be healthy based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and urine chemistry) at Visit 0.
3.0 Inclusion IN06 Women of childbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin urine test at
Visit 0 and Visit 1. Women that are postmenopausal or
permanently sterilized will be considered as not having
reproductive potential.
3.0 Inclusion IN07_3 WOCBP must agree to practice two highly effective forms
of contraception during the trial, starting after Visit 0 and
continuously until 60 d after receiv ing the last
immunization.
3.0 Inclusion IN08_3 WOCBP must confirm that they practiced at least one
highly effective form of contraception for the 14 d prior to
Visit 0.
3.0 Inclusion IN09 WOCBP must agree not to donate eggs (ova, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving the
last immunization.
090177e19673667b\Final\Final On: 08-Mar-2021 02:02 (GMT)
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Version Category IETESTCD Full Text of Criterion
3.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partner of
childbearing potential during the trial, starting after Visit 0
and continuously until 60 d after receiving the last
immunization.
3.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
3.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visit 0.
3.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Visit 0 and continuously until 28 d after
receiving the last immunization.
3.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the residual
symptoms will not compromise their well-being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confound the protocol -specified
assessments.
3.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial, starting af ter Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
3.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intolerance to
the planned IMP including any excipients of the IMP.
3.0 Exclusion EX04 Had any medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years which,
in the opinion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could prevent, limi t, or confound the protocol -specified
assessments.
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3.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuously until at least 90 d after receiving
the last immunization.
3.0 Exclusion EX06 Had any chronic use (more than 14 continuous days) of any
systemic medications, including immunosuppressant or
other immune -modifying drugs, within the 6 months prior
to Visit 0 unless in the opinion of the investigator, the
medication would not prevent, limit, or confound th e
protocol -specified assessments or could compromise
subject safety.
3.0 Exclusion EX07 Received any vaccination within the 28 d prior to Visit 0.
3.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
3.0 Exclusion EX09 Had administration of another investigational product
including vaccines within 60 d or 5 half -lives (whichever is
longer), prior to Visit 0.
3.0 Exclusion EX10 Have a known history or a positive test of any of HIV 1 or
2, Hepatitis B, or Hepatitis C, within the 30 d prior to Visit
0.
3.0 Exclusion EX11_3 Have a positive PCR -based test for SARS -CoV-2 within
the 30 d prior to Visit 1.
3.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepine s, barbiturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) result at Visit 0 or Visit 1.
3.0 Exclusion EX13 Have a positive breath alcohol test at Visit 0 or Visit 1.
3.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles.
3.0 Exclusion EX15 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
3.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or dependent person, such as an
employee or student of the trial site).
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3.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psyc hological, or social conditions
which, in the opinion of the investigator, could compromise
their well -being if they participate as trial subjects in the
trial, or that could prevent, limit, or confound the protocol -
specified assessments.
3.0 Exclusion EX18 Have a history of hypersensitivity or serious reactions to
previous vaccinations.
3.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a previous vaccination.
3.0 Exclusion EX20 Have a history of narcolepsy.
3.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
3.0 Exclusion EX22 Have a history of or suspected immunosuppressive
condition, acquired or congenital, as determined by medical
history and/or physical examinatio n at Visit 0.
3.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability to observe local reactions at the injection site.
3.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or blood products or injury, within the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunization.
3.0 Exclu sion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
3.0 Exclusion EX26 Have had contact with persons diagnosed with COVID -19
or who tested positive for SARS -CoV-2 by any diagnostic
test within the 30 d prior to Visit 1.
3.0 Exclusion EX27 Are soldiers, subjects in detention, CRO or sponsor staff or
their family members.
4.0 Inclusion IN01_3 Have given informed consent by signing the informed
consent form (ICF) before initiation of any trial -specific
procedures.
090177e19673667b\Final\Final On: 08-Mar-2021 02:02 (GMT)
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4.0 Inclusion IN02 They must be willing and able to comply with scheduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions (e.g., to practice social distancing and to follow
good practices t o reduce their chances of being infected or
spreading COVID -19), and other requirements of the trial.
4.0 Inclusion IN03 They must be able to understand and follow trial -related
instructions.
4.0 Inclusion IN04 They must be aged from 18 to 55 years, have a body mass
index over 19 kg/m2 and under 30 kg/m2, and weigh at
least 50 kg at Visit 0.
4.0 Inclusion IN05 They must be healthy based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and urine chemistry) at Visit 0.
4.0 Inclusion IN06 Women of childbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin urine test at
Visit 0 and Visit 1. Women that are postmenopausal or
permanently sterilized will be considered as not having
reproductive potential.
4.0 Inclusion IN07_4 WOCBP must agree to practice a highly effective form of
contraception dur ing the trial, starting after Visit 0 and
continuously until 60 d after receiving the last
immunization.
4.0 Inclusion IN08_3 WOCBP must confirm that they practiced at least one
highly effective form of contraception for the 14 d prior to
Visit 0.
4.0 Inclusion IN09 WOCBP must agree not to donate eggs (ova, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving the
last immunization.
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Version Category IETESTCD Full Text of Criterion
4.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partner of
childbearing potential during the trial, starting after Visit 0
and continuously until 60 d a fter receiving the last
immunization.
4.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
4.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visit 0.
4.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Visit 0 and continuously until 28 d after
receiving the last immunization.
4.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the r esidual
symptoms will not compromise their well -being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confound the protocol -specified
assessments.
4.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial, starting after Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
4.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intolerance to
the planned IMP including any excipients o f the IMP.
4.0 Exclusion EX04 Had any medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years which,
in the opinion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could prevent, limit, or confound the protocol -specified
assessments.
090177e19673667b\Final\Final On: 08-Mar-2021 02:02 (GMT)
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4.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuously until at least 90 d after receiving
the last immuniz ation.
4.0 Exclusion EX06_4 Had any chronic use (more than 14 continuous days) of any
systemic medications, including immunosuppressant's or
other immune -modifying drugs, within the 6 months prior
to Visit 0 unless in the opinion of the investigator, the
medication would not prevent, limit, or confound the
protocol -specified assessments or could compromise
subject safety.
4.0 Exclusion EX07 Received any vaccination within the 28 d prior to Visit 0.
4.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
4.0 Exclusion EX09_4 Had administration of another investigational medicinal
product including vaccines within 60 d or 5 half -lives
(whichever is longer), prior to Visit 0.
4.0 Exclusion EX10 Have a known history or a positive test of any of HIV 1 or
2, Hepatitis B, or Hepatitis C, within the 30 d prior to Visit
0.
4.0 Exclusion EX11_3 Have a positive PCR -based test for SARS -CoV-2 within
the 30 d prior to Visit 1.
4.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepines, barbiturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) result at Visit 0 or Visit 1.
4.0 Exclusion EX13 Have a positive breath alcohol test at Visit 0 or Visit 1.
4.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles.
4.0 Exclusion EX15 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
4.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or dependent person, such as an
employee or student of the trial site).
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4.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psychological, or social conditions
which, in the opinion of the investigator, could compromise
their well -being if they participate as trial subjects in the
trial, or that could prevent, limit, or confound the protocol -
specified assessments.
4.0 Exclusion EX18 Have a history of hypersensitivity or serious reactions to
previous vaccinations.
4.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a pr evious vaccination.
4.0 Exclusion EX20 Have a history of narcolepsy.
4.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
4.0 Exclusion EX22 Have a history of or suspected immunosuppressive
condition, acquired or congenital, as determined by medical
history and/or physical examination at Visit 0.
4.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability t o observe local reactions at the injection site.
4.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or blood products or injury, within the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunization.
4.0 Exclusion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
4.0 Exclusion EX26 Have had contact with persons diagnosed with COVID -19
or who tested positive for SARS -CoV-2 by any diagnostic
test within the 30 d prior to Visit 1.
4.0 Exclusion EX27 Are soldiers, subjects in detention, CRO or sponsor staff or
their family members.
5.0 Inclusion IN01_3 Have given informed consent by signing the informed
consent form (ICF) before initiation of any trial -specific
procedures.
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5.0 Inclusion IN02 They must be willing and able to comply with sch eduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions (e.g., to practice social distancing and to follow
good practices to reduce their chances of being infected or
spreading COVID -19), and other requirements of the trial.
5.0 Inclus ion IN03 They must be able to understand and follow trial -related
instructions.
5.0 Inclusion IN04 They must be aged from 18 to 55 years, have a body mass
index over 19 kg/m2 and under 30 kg/m2, and weigh at
least 50 kg at Visit 0.
5.0 Inclusion IN05 They must be healthy based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and urine chemist ry) at Visit 0.
5.0 Inclusion IN06 Women of childbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin urine test at
Visit 0 and Visit 1. Women that are postmenopausal or
permanently sterilized will be considered as not having
reproductive potential.
5.0 Inclusion IN07_4 WOCBP must agree to practice a highly effective form of
contraception during the trial, starting after Visit 0 and
continuously until 60 d after receiving the last
immunization.
5.0 Inclusion IN08_3 WOCBP must confirm that they practiced at least one
highly ef fective form of contraception for the 14 d prior to
Visit 0.
5.0 Inclusion IN09 WOCBP must agree not to donate eggs (ova, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving t he
last immunization.
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5.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partner of
childbearing potential during the trial, starting a fter Visit 0
and continuously until 60 d after receiving the last
immunization.
5.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
5.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visit 0.
5.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Visit 0 and continuously until 28 d after
receiving the last immunizat ion.
5.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the residual
symptoms will not compromise their well -being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confound the protocol -specified
assessments.
5.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial, starting after Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
5.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intoler ance to
the planned IMP including any excipients of the IMP.
5.0 Exclusion EX04 Had any medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years which,
in the opinion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could prevent, limit, or confound the protocol -specified
assessments.
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5.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuo usly until at least 90 d after receiving
the last immunization.
5.0 Exclusion EX06_4 Had any chronic use (more than 14 continuous days) of any
systemic medications, including immunosuppressant's or
other immune -modifying drugs, within the 6 months prior
to Visit 0 unless in the opinion of the investigator, the
medication would not prevent, limit, or confound the
protocol -specified assessments or could compromise
subject safety.
5.0 Exclusion EX07 Received any vaccination within the 28 d prior to Visit 0.
5.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
5.0 Exclusion EX09_4 Had administration of another investigational medicinal
product including vaccines within 60 d or 5 half-lives
(whichever is longer), prior to Visit 0.
5.0 Exclusion EX10 Have a known history or a positive test of any of HIV 1 or
2, Hepatitis B, or Hepatitis C, within the 30 d prior to Visit
0.
5.0 Exclusion EX11_3 Have a positive PCR -based test for SARS -CoV-2 within
the 30 d prior to Visit 1.
5.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepines, barbiturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) res ult at Visit 0 or Visit 1.
5.0 Exclusion EX13 Have a positive breath alcohol test at Visit 0 or Visit 1.
5.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles.
5.0 Exclusion EX15 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
5.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or dependent person, such as an
employee or student of the trial site).
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5.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psychological, or social conditions
which, in the opinion of the investigator, could compromise
their well -being if they parti cipate as trial subjects in the
trial, or that could prevent, limit, or confound the protocol -
specified assessments.
5.0 Exclusion EX18 Have a history of hypersensitivity or serious reactions to
previous vaccinations.
5.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a previous vaccination.
5.0 Exclusion EX20 Have a history of narcolepsy.
5.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
5.0 Exclusion EX22 Have a history of or suspected immunosuppressive
condition, acquired or congenital, as determined by medical
history and/or physical examination at Visit 0.
5.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability to observe local reactions at the injection site.
5.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or blood products or injury, within the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunization.
5.0 Exclusion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
5.0 Exclusion EX26 Have had contact with persons diagnosed with COVID -19
or who tested positive for SARS -CoV-2 by any diagnostic
test within the 30 d prior to Visit 1.
5.0 Exclusion EX27 Are soldiers, subjects in detention, CRO or sponsor staff or
their family members.
6.0 Inclusion IN01_3 Have given informed consent by signing the informed
consent form (ICF) before initiation of any trial -specific
procedures.
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6.0 Inclusion IN02 They must be willing and able to comply with scheduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions (e.g., to practice social distancing and to follow
good practices to reduce their chances of being infected or
spreading COVID -19), and other requirements of the trial.
6.0 Inclusion IN03 They must be able to understand and follow trial -related
instructions.
6.0 Inclusion IN04_6 They must be aged from 18 to 55 years (Cohorts 1 to 8) or
be aged 65 to 85 years (elderly subject cohorts), have a
body mass index over 19 kg/m2 and un der 30 kg/m2, and
weigh at least 50 kg at Visit 0.
6.0 Inclusion IN05 They must be healthy based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and urine chemistry) at Visit 0.
6.0 Inclusion IN06 Women of childbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin urine test at
Visit 0 and Visit 1. Women that are po stmenopausal or
permanently sterilized will be considered as not having
reproductive potential.
6.0 Inclusion IN07_4 WOCBP must agree to practice a highly effective form of
contraception during the trial, starting after Visit 0 and
continuously until 60 d after receiving the last
immunization.
6.0 Inclusion IN08_3 WOCBP must confirm that they practiced at least one
highly effective form of contraception for the 14 d prior to
Visit 0.
6.0 Inclusion IN09 WOCBP must agree not to donate eggs (ova, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving the
last immunization.
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6.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partne r of
childbearing potential during the trial, starting after Visit 0
and continuously until 60 d after receiving the last
immunization.
6.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
6.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visit 0.
6.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Vi sit 0 and continuously until 28 d after
receiving the last immunization.
6.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the residual
symptoms will not compromise their well -being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confo und the protocol -specified
assessments.
6.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial, starting after Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
6.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intolerance to
the planned IMP including any excipients of the IMP.
6.0 Exclusion EX04 Had any medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years wh ich,
in the opinion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could prevent, limit, or confound the protocol -specified
assessments.
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6.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuously until at least 90 d after receiving
the last immunization.
6.0 Exclusion EX06_4 Had any chronic use (more than 14 continuous days) of any
systemic medications, including immunosuppressant's or
other immune -modifying drugs, within the 6 months prior
to Visit 0 unless in the opinion of the investigator, the
medication would not prevent, limit, or confound the
protocol -specified assessments or could compromise
subject safety.
6.0 Exclusion EX07 Receiv ed any vaccination within the 28 d prior to Visit 0.
6.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
6.0 Exclusion EX09_4 Had administration of another investigational medicinal
product including vaccines within 60 d or 5 half -lives
(whichever is longer), prior to Visit 0.
6.0 Exclusion EX10 Have a known history or a positive test of any of HIV 1 or
2, Hepatitis B, or Hepatitis C, within the 30 d prior t o Visit
0.
6.0 Exclusion EX11_3 Have a positive PCR -based test for SARS -CoV-2 within
the 30 d prior to Visit 1.
6.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepines, barbiturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) result at Visit 0 or Visit 1.
6.0 Exclusion EX13 Have a positive breath alcohol test at Visit 0 or Visit 1.
6.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles.
6.0 Exclusion EX15 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
6.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or dependent person, such as an
employee or student of the trial site).
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6.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psychological, or social conditions
which, in the o pinion of the investigator, could compromise
their well -being if they participate as trial subjects in the
trial, or that could prevent, limit, or confound the protocol -
specified assessments.
6.0 Exclusion EX18 Have a history of hypersensitivity or seriou s reactions to
previous vaccinations.
6.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a previous vaccination.
6.0 Exclusion EX20 Have a history of narcolepsy.
6.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
6.0 Exclusion EX22 Have a history of or suspected immunosuppressive
condition, acquired or congenital, as determined by medical
history and/or physical examination at Visit 0.
6.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability to observe local reactions at the injection site.
6.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or b lood products or injury, within the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunization.
6.0 Exclusion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
6.0 Exclusion EX26 Have had contact with persons diagnosed with COVID -19
or who tested positive for SARS -CoV-2 by any diagnostic
test within the 30 d prior to Visit 1.
6.0 Exclusion EX27 Are soldiers, subjects in detention, CRO or sponsor staff or
their family members.
7.0 Inclusion IN01_3 Have given informed consent by signing the informed
consent form (ICF) before initiation of any trial -specific
procedures.
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7.0 Inclusion IN02 They must be willing and able to comply with scheduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions (e.g., to practice social distancing and to follow
good practices to reduce their chances of being infected or
spread ing COVID -19), and other requirements of the trial.
7.0 Inclusion IN03 They must be able to understand and follow trial -related
instructions.
7.0 Inclusion IN04_7 For younger subject cohorts, volunteers must be aged 18 to
55 years, have a body mass index over 19 kg/m2 and under
30 kg/m2, and weigh at least 50 kg at Visit 0. OR For
older adult cohorts, volunteers must be aged 56 to 85 years,
have a body mass index over 19 kg/m2 and under 30
kg/m2, and weigh at least 50 kg at Visit 0.
7.0 Inclusion IN05_ 7 They must be healthy, in the clinical judgment of the
investigator, based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and urine chemistry) at Visit 0. Note: Healthy
volunteers with pre -existing stable disease, defined as
disease not requiring significant change in therapy or
hospitalization for worsening disease during the 6 weeks
before enrollment, can be included.
7.0 Inclusion IN06 Women of childbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin urine test at
Visit 0 and Visit 1. Women that are postmenopausal or
permanently sterilized will be considered as not having
reproductive potential.
7.0 Inclusion IN07_7 WOCBP must agree to practice a highly effective form of
contraception during the trial, starting after Visit 0 and
continuously until 60 d after receiving the last
immunization. WOCBP must agree to require their male
partners to use condoms during sexual contact (unless male
partners are sterilized or infertile).
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7.0 Inclusion IN08_3 WOCBP must confirm that they practiced at least one
highly effective form of contraception for the 14 d prior to
Visit 0.
7.0 Inclusion IN09 WOCBP must agree not to donate eggs (ova, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving the
last immunization.
7.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partner of
childbearing potential during the trial, starting after Visit 0
and continuously until 60 d after receiving the last
immunization.
7.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
7.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visit 0.
7.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Visit 0 and continuously until 28 d after
receiving the last immunization.
7.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the residual
symptoms will not compromise their well-being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confound the protocol -specified
assessments.
7.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial, starting af ter Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
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7.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intolerance to
the planned IMP including any excipients of the IMP.
7.0 Exclusion EX04 Had any medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years which,
in the opinion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could prevent, limi t, or confound the protocol -specified
assessments.
7.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuously until at least 90 d after receiving
the last immunization.
7.0 Exclusion EX06_7 Had any chronic use (more than 21 continuous days) of any
systemic medications, including immunosuppressant's or
other immune -modifying drugs, within the 6 months prior
to Visit 0 unless in the opinion of the investigator, the
medication would not prevent, limit, or confound the
protocol -specified assessments or could compromise
subject safety. Note: Healthy participants with preexisting
stable disease, defined as disease not requiring significant
change in therapy or hospitalization for worsening disease
during t he 6 weeks before enrollment, can be included.
7.0 Exclusion EX07 Received any vaccination within the 28 d prior to Visit 0.
7.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
7.0 Exclusion EX09_4 Had administration of another investigational medicinal
product including vaccines within 60 d or 5 half -lives
(whichever is longer), prior to Visit 0.
7.0 Exclusion EX10 Have a known history or a positive test of any of HIV 1 or
2, Hepatitis B, or Hepatitis C, within the 30 d prior to Visit
0.
7.0 Exclusion EX11_3 Have a positive PCR -based test for SARS -CoV-2 within
the 30 d prior to Visit 1.
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7.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepines, barb iturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) result at Visit 0 or Visit 1.
7.0 Exclusion EX13 Have a positive breath alcohol test at Visit 0 or Visit 1.
7.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles.
7.0 Exclusion EX15 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
7.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or dependent person, such as an
employee or student of the trial site).
7.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psyc hological, or social conditions
which, in the opinion of the investigator, could compromise
their well -being if they participate as trial subjects in the
trial, or that could prevent, limit, or confound the protocol -
specified assessments.
7.0 Exclusion EX18 Have a history of hypersensitivity or serious reactions to
previous vaccinations.
7.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a previous vaccination.
7.0 Exclusion EX20 Have a history of narcolepsy.
7.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
7.0 Exclusion EX22 Have a history of or suspected immunosuppressive
condition, acquired or congenital, as determined by medical
history and/or physical examinatio n at Visit 0.
7.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability to observe local reactions at the injection site.
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7.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or blood products or injury, within the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunization.
7.0 Exclu sion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
7.0 Exclusion EX26 Have had contact with persons diagnosed with COVID -19
or who tested positive for SARS -CoV-2 by any diagnostic
test within the 30 d prior to Visit 1.
7.0 Exclusion EX27 Are soldiers, subjects in detention, CRO or sponsor staff or
their family members.
7.0 Exclusion EX28 Regular receipt of inhaled/nebulized corticosteroids.
7.0 Exclusion EX29 For older adults only: Have a condition known to put them
at high risk for severe COVID -19, including those with any
of the following risk factors: Hypertension, Diabetes
mellitus, Chronic pulmonary disease, Asthma, Chronic
liver disease, Known Stage 3 or worse chr onic kidney
disease (glomerular filtration rate <60 mL/min/1.73 m2),
BMI >= 30 kg/m2, Anticipating the need for
immunosuppressive treatment within the next 6 months,
Resident in a long -term facility, Current vaping or smoking
(occasional smoking is accepta ble), History of chronic
smoking within the prior year.
8.0 Inclusion IN01_3 Have given informed consent by signing the informed
consent form (ICF) before initiation of any trial -specific
procedures.
8.0 Inclusion IN02 They must be willing and able to comply with scheduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions (e.g., to practice social distancing and to follow
good practices to reduce their chances of being infected or
spreading COVID -19), and other requirements of the tri al.
8.0 Inclusion IN03 They must be able to understand and follow trial -related
instructions.
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8.0 Inclusion IN04_7 For younger subject cohorts, volunteers must be aged 18 to
55 years, have a body mass index over 19 kg/m2 and under
30 kg/m2, and weigh at least 50 kg at Visit 0. OR For
older adult cohorts, volunteers must be aged 56 to 85 years,
have a body mass index over 19 kg/m2 and under 30
kg/m2, and weigh at least 50 kg at Visit 0.
8.0 Inclusion IN05_7 They must be healthy, in the clinical judgment of the
investigator, based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and uri ne chemistry) at Visit 0. Note: Healthy
volunteers with pre -existing stable disease, defined as
disease not requiring significant change in therapy or
hospitalization for worsening disease during the 6 weeks
before enrollment, can be included.
8.0 Inclus ion IN06 Women of childbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin urine test at
Visit 0 and Visit 1. Women that are postmenopausal or
permanently sterilized will be considered as not having
reproductive potential.
8.0 Inclusion IN07_7 WOCBP must agree to practice a highly effective form of
contraception during the trial, starting after Visit 0 and
continuously until 60 d after receiving the last
immunization. WOCBP must agree to require their male
partners to use condoms during sexual contac t (unless male
partners are sterilized or infertile).
8.0 Inclusion IN08_3 WOCBP must confirm that they practiced at least one
highly effective form of contraception for the 14 d prior to
Visit 0.
8.0 Inclusion IN09 WOCBP must agree not to donate eggs (o va, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving the
last immunization.
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8.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partner of
childbearing potential during the trial, starting after Visit 0
and continuously until 60 d after receiving the last
immunization.
8.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
8.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visi t 0.
8.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Visit 0 and continuously until 28 d after
receiving the last immunization.
8.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the residual
symptoms will not comp romise their well -being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confound the protocol -specified
assessments.
8.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial , starting after Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
8.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intolerance to
the planned IMP including any excipients of the IMP.
8.0 Exclusion EX04 Had any medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years which,
in the opinion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could preve nt, limit, or confound the protocol -specified
assessments.
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8.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuously until at least 90 d after receiving
the last immunization.
8.0 Exclusion EX06_7 Had any chron ic use (more than 21 continuous days) of any
systemic medications, including immunosuppressant's or
other immune -modifying drugs, within the 6 months prior
to Visit 0 unless in the opinion of the investigator, the
medication would not prevent, limit, or co nfound the
protocol -specified assessments or could compromise
subject safety. Note: Healthy participants with preexisting
stable disease, defined as disease not requiring significant
change in therapy or hospitalization for worsening disease
during the 6 weeks before enrollment, can be included.
8.0 Exclusion EX07 Received any vaccination within the 28 d prior to Visit 0.
8.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
8.0 Exclusion EX09_4 Had administration of another investigational medicinal
product including vaccines within 60 d or 5 half -lives
(whichever is longer), prior to Visit 0.
8.0 Exclusion EX10 Have a known history or a positive test of any of HIV 1 or
2, Hepatitis B, or Hepatitis C, within the 30 d prior to Visit
0.
8.0 Exclusion EX11_3 Have a positive PCR -based test for SARS -CoV-2 within
the 30 d prior to Visit 1.
8.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepines, barb iturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) result at Visit 0 or Visit 1.
8.0 Exclusion EX13 Have a positive breath alcohol test at Visit 0 or Visit 1.
8.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles.
8.0 Exclusion EX15 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
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8.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or dependent person, such as an
employee or student of the trial site).
8.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psychological, or social conditions
which, in the opinion of the investigator, could compromise
their well -being if they participate as trial subjects in the
trial, or that could prevent, limit, or confound the protocol -
specified assessments.
8.0 Exclusion EX18 Have a history of hypersensitivity or serious reactions to
previous vaccinations.
8.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a previous vaccination.
8.0 Exclusion EX20 Have a history of narcolepsy.
8.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
8.0 Exclusion EX22 Have a history of or suspected immunosuppressive
condition, acquired or congenital, as determined by medical
history and/or ph ysical examination at Visit 0.
8.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability to observe local reactions at the injection site.
8.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or blood products or injury, within the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunizati on.
8.0 Exclusion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
8.0 Exclusion EX26 Have had contact with persons diagnosed with COVID -19
or who tested positive for SARS -CoV-2 by any diagnostic
test within the 30 d prior to Visit 1.
8.0 Exclusion EX27 Are soldiers, subjects in detention, CRO or sponsor staff or
their family members.
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8.0 Exclusion EX28 Regular receipt of inhaled/nebulized corticosteroids.
8.0 Exclusion EX29 _8 For older adults only: Have a condition known to put them
at high risk for severe COVID -19, including those with any
of the following risk factors: Hypertension , Diabetes
mellitus, Chronic pulmonary disease, Asthma, Chronic
liver disease ,Known Stage 3 or worse chronic kidney
disease (glomerular filtration rate <60 mL/min/1.73
m2),Anticipating the need for immunosuppressive
treatment within the next 6 months ,Resident in a long -term
facility, Current vaping or smoking (occasional smoking is
acceptable),Hist ory of chronic smoking within the prior
year.
9.0 Inclusion IN01_3 Have given informed consent by signing the informed
consent form (ICF) before initiation of any trial -specific
procedures.
9.0 Inclusion IN02 They must be willing and able to comply with scheduled
visits, treatment schedule, laboratory tests, lifestyle
restrictions (e.g., to practice social distancing and to follow
good practices to reduce their chances of being infected or
spreading COVID -19), and other requirements of the trial.
9.0 Inclusion IN03 They must be able to understand and follow trial -related
instructions.
9.0 Inclusion IN04_7 For younger subject cohorts, volunteers must be aged 18 to
55 years, have a body mass index over 19 kg/m2 and under
30 kg/m2, and weigh at least 50 kg at Visit 0. OR For
older adult cohorts, volunteers must be aged 56 to 85 years,
have a body mass index over 19 kg/m2 and under 30
kg/m2, and weigh at least 50 kg at Visit 0.
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9.0 Inclusion IN05_ 9 They must be healthy, in the clinical judgment of the
investigator, based on medical history, physical
examination, 12 -lead ECG, vital signs (systolic/diastolic
blood pressure, pulse rate, body temperature, respiratory
rate), and clinical laboratory tests (blood chemistry,
hematology, and urine chemistry) at V isit 0.
Note: Healthy volunteers with pre -existing stable disease,
defined as disease not requiring significant change in
therapy or hospitalization for worsening disease during the
6 wks before enrollment, can be included.
OR
For the immunocompromised cohort (Cohort 13);
volunteers who have previously received solid organ
transplant, or peripheral blood stem cell transplantation ≥6
months after transplantation, or individuals with HIV
infection with a CD4+ T -cell count of ≥200 x 106 /L.
Individuals wit h lower T -cell counts will be excluded from
the trial on the basis that this represents a significant
medical complication. In the clinical judgment of the
investigator, volunteers must be immunocompromised but
otherwise healthy. After consultation with th e Medical
Monitor, this may include individuals receiving
immunosuppressant therapy due to another confounding
disease at least
2 wks prior to enrollment and/or at least 6 wks following
immunization with
BNT162b2, and/or individuals with immunosuppressive
treatment of an autoimmune disease if the disease is stable.
9.0 Inclusion IN06 Women of childbearing potential (WOCBP) must have a
negative beta -human chorionic gonadotropin urine test at
Visit 0 and Visit 1. Women that are postmenopaus al or
permanently sterilized will be considered as not having
reproductive potential.
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9.0 Inclusion IN07_7 WOCBP must agree to practice a highly effective form of
contraception during the trial, starting after Visit 0 and
continuously until 60 d after rec eiving the last
immunization. WOCBP must agree to require their male
partners to use condoms during sexual contact (unless male
partners are sterilized or infertile).
9.0 Inclusion IN08_3 WOCBP must confirm that they practiced at least one
highly effective form of contraception for the 14 d prior to
Visit 0.
9.0 Inclusion IN09 WOCBP must agree not to donate eggs (ova, oocytes) for
the purposes of assisted reproduction during trial, starting
after Visit 0 and continuously until 60 d after receiving the
last immunization.
9.0 Inclusion IN10 Men who are sexually active with a WOCBP and have not
had a vasectomy must agree to practice a highly effective
form of contraception with their female partner of
childbearing potential during the trial, starting after Visit 0
and continuously until 60 d after receiving the last
immunization.
9.0 Inclusion IN11 Men must be willing to refrain from sperm donation,
starting after Visit 0 and continuously until 60 d after
receiving the last immunization.
9.0 Inclusion IN12 They must have confirmation of their health insurance
coverage prior to Visit 0.
9.0 Inclusion IN13 They must agree to not be vaccinated during the trial,
starting after Visit 0 and continuously until 28 d after
receiving the last immunization.
9.0 Exclusion EX01 Have had any acute illness, as determined by the
investigator, with or without fever, within 72 h prior to the
first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is
allowable if, in the opinion of the investigator, the residual
symptoms will not compromise their well-being if they
participate as trial subjects in the trial, or that could
prevent, limit, or confound the protocol -specified
assessments.
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9.0 Exclusion EX02 Are breastfeeding on the day of Visit 0 or who plan to
breastfeed during the trial, starting after Visit 0 and
continuously until at least 90 d after receiving the last
immunization.
9.0 Exclusion EX03 Have a known allergy, hypersensitivity, or intolerance to
the planned IMP including any excipients of the IMP.
9.0 Exclusion EX04 Had an y medical condition or any major surgery (e.g.,
requiring general anesthesia) within the past 5 years which,
in the opinion of the investigator, could compromise their
well-being if they participate as trial subjects in the trial, or
that could prevent, li mit, or confound the protocol -specified
assessments.
9.0 Exclusion EX05 Have any surgery planned during the trial, starting after
Visit 0 and continuously until at least 90 d after receiving
the last immunization.
9.0 Exclusion EX06_ 9 Had any chronic use (more than 21 continuous days) of any
systemic medications, including immunosuppressants or
other immune -modifying drugs (except for Cohort 13),
within the 6 months prior to Visit 0 unless in the opinion of
the investigator, the medicat ion would not prevent, limit, or
confound the protocolspecified assessments or could
compromise subject safety.
Note: Healthy volunteers with pre -existing stable disease,
defined as disease not requiring significant change in
therapy or hospitalization fo r worsening disease during the
6 wks before enrollment, can be included.
9.0 Exclusion EX07 Received any vaccination within the 28 d prior to Visit 0.
9.0 Exclusion EX08 Had administration of any immunoglobulins and/or any
blood products within the 3 months prior to Visit 0.
9.0 Exclusion EX09_4 Had administration of another investigational medicinal
product including vaccines within 60 d or 5 half -lives
(whichever is longer), prior to Visit 0.
9.0 Exclusion EX10 _9 Have a known history or a positive test for any of Hepatitis
B, or Hepatitis C, or HIV 1 or 2 (except for Cohort 13)
within the 30 d prior to Visit 0
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9.0 Exclusion EX11_3 Have a positive PCR -based test for SARS -CoV-2 within
the 30 d prior to Visit 1.
9.0 Exclusion EX12 Have a positive drugs of abuse (for amphetamines,
benzodiazepines, barbiturates, cocaine, cannabinoids,
opiates, methadone, methamphetamines, phencyclidine,
and tricyclic antidepressants) result at Visit 0 or Visit 1.
9.0 Exclusion EX13 Have a positive breath al cohol test at Visit 0 or Visit 1.
9.0 Exclusion EX14 Previously participated in an investigational trial involving
lipid nanoparticles.
9.0 Exclusion EX15 _9 Are subject to exclusion periods from other investigational
trials or simultaneous participation in another clinical trial.
When entering the follow -up phase, i.e., after completing
the EoT visit, subjects are allowed to participate in other
clinical trial s not investigating COVID -19 vaccines or
treatments.
9.0 Exclusion EX16 Have any affiliation with the trial site (e.g., are close
relative of the investigator or dependent person, such as an
employee or student of the trial site).
9.0 Exclusion EX17 Have a history (within the past 5 years) of substance abuse
or known medical, psychological, or social conditions
which, in the opinion of the investigator, could compromise
their well -being if they participate as trial subjects in the
trial, or that could pre vent, limit, or confound the protocol -
specified assessments.
9.0 Exclusion EX18 Have a history of hypersensitivity or serious reactions to
previous vaccinations.
9.0 Exclusion EX19 Have a history of Guillain -Barré Syndrome within 6 wks
following a previous vaccination.
9.0 Exclusion EX20 Have a history of narcolepsy.
9.0 Exclusion EX21 Have history of alcohol abuse or drug addiction within 1
year before Visit 0.
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9.0 Exclusion EX22 _9 (Except for Cohort 13) Have a history of or suspected
immunosuppressive condition, acquired or congenital, as
determined by medical history and/or physical examination
at Visit 0.
9.0 Exclusion EX23 Have any abnormality or permanent body art (e.g., tattoo)
that, in the opinion of the investigator, would obstruct the
ability to observe local reactions at the injection site.
9.0 Exclusion EX24 Have had any blood loss >450 mL, e.g., due to donation of
blood or blood products or injury, within the 7 d prior to
Visit 0 or plan to donate blood during the trial, starting
after Visit 0 and continuously until at least 7 d after
receiving the last immunization.
9.0 Exclusion EX25 Symptoms of COVID -19, e.g., respiratory symptoms,
fever, cough, shortness of breath and breathing difficulties.
9.0 Exclusion EX26 Have had contact with persons diagnosed with COVID -19
or who tested positive for SARS -CoV-2 by any diagnostic
test within the 30 d prior to Visit 1.
9.0 Exclusion EX27 Are soldiers, subjects in detention, CRO or sponsor staff or
their family members.
9.0 Exclusion EX28 Regular receipt of inhaled/nebulized corticosteroids.
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9.0 Exclusion EX29_ 9 For older volunteers and for Cohort 13 only: Have a
condition known to put th em at high risk for severe
COVID -19, including those with any of the following risk
factors:
− Hypertension.
− Diabetes mellitus.
− Chronic obstructive pulmonary disease.
− Asthma.
− Chronic liver disease.
− Known Stage 3 or worse chronic kidney disease
(glomerular filtration rate <60 mL/min/1.73 m2).
− Serious heart conditions, such as heart failure, coronary
artery disease, or cardiomyopathies.
− Sickle cell disease.
− Cancer (except for Cohort 13).
− Are immune compromised due to stem cell or organ -
transplantation with significant medical complications such
as acute or chronic graft rejection or graft versus host
disease requiring intensive immunosuppressive treatment,
transplant failure or infectious complications or other
conditions that would be considered a contraindication for
vaccination.
− Are immune compromised due to HIV infection with a
CD4+ count of < 200 x 106 /L at screening or significant
medical complications such as opportunistic infect ions,
malignant complications (e.g., lymphoma, Kaposi
sarcoma), other organ manifestations consistent with
advanced AIDS or other conditions that would be
considered a contraindication for vaccination.
− Resident in a long term facility.
− Current vaping or smoking (occasional smoking is
acceptable).
− History of chronic smoking within the prior year.
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