Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine (BNT162b1) in Chinese Healthy Subjects: A Phase I, Randomized, Placebo-controlled, Observer-blind Study
Phase: PHASE1
Conditions: SARS-CoV-2
Sponsor: BioNTech SE

 
Confidential  
Clinical Protocol 
Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine (BNT162b1) in Chinese Healthy 
Subjects: A Phase I, Randomized, Placebo-controlled, Observer-blind Study 
Protocol No.: BNT162-03 
Clinical Phase: Phase I 
 
Authorized Representative (Signature) 
Aimin Hui, M.D. 
Fosun Pharma Global R&D President, Chief Medical Officer and Chair of the Clinical and Registration 
Review Committee   
Shanghai Fosun Pharmaceutical Development, Inc. 
1289 Yishan Road, Shanghai, China 200233 
Signed by: 
 
Date: 
 
 
Özlem Türeci, M.D. 
Chief Medical Officer  
BioNTech SE 
An der Goldgrube 12, Mainz, German 55131 
Signed by: 
 
Date: 
 
 
 
 
 
Execution Organization 
Shanghai Fosun Pharmaceutical Development, Inc. 
1289 Yishan Road, Shanghai 
China 200233 
Sponsor 
BioNTech RNA Pharmaceuticals GmbH 
An der Goldgrube 12, 55131 Mainz 
Germany 
 
Version: Protocol Amendment 3-Version 3.0  
Date: 5 AUG 2020 
Compliance: This study will be conducted in compliance with this protocol, Good Clinical Practice, and applicable regulatory requirements. 
Confidentiality Statement 
The information in this document contains trade secrets and commercial information that are privileged or confidential and may not be 
disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the information is disclosed must 
be informed that the information is privileged or confidential and may not be further disclosed by them. These restrictions on disclosure will 
apply equally to all future information supplied to you that is indicated as privileged or confidential.

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 2 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
1.0 
ADMINISTRATIVE INFORMATION  
1.1 Contacts  
A separate contact information list will be provided to study sites. Contact information is also 
provided in Table 1.  
The Fosun will provide investigators with site-specific emergency medical contact information 
cards to be carried by each subject.  
General advice on protocol procedures should be obtained through the monitor assigned to the 
study site. 
Table 1  Contact information  
Issue  
Contact  
Serious 
adverse 
event 
and 
pregnancy reporting  
Fosun Pharma  
 
Telephone numbers for serious adverse event and pregnancy 
reporting will be provided to the site   
Medical Monitor  
(medical advice on conduct of 
protocol or vaccine)  
Emergency medical contact information will be provided to 
the site   
1.2 Document History 
Document History 
Date 
Protocol No. and Version No. Valid Range 
Initial version 
20 APR 2020 
BNT162-03-CN, Version 1.0 
China 
Initial submitted version 
20 MAY 2020 
BNT162-03, Version 1.0 
China 
Amendment 1 
10 JUL 2020 
BNT162-03, Version 2.0 
China 
Amendment 2 
26 JUL 2020 
BNT162-03, Version 2.1 
China 
Amendment 3 
5 AUG 2020 
BNT162-03, Version 3.0 
China 
 
1.3 Approval  

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 3 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
Signature Page for Investigator 
We have read this clinical study protocol, protocol number: BNT162-03, version number: V3.0 
(version date AUG 5, 2020). I agree to perform relevant duties in accordance with Chinese laws, 
Declaration of Helsinki, NMPA GCP and this study protocol. This study can only be carried out 
after obtaining the approval from the ethics committee. 
During the implementation of the study, I will strictly follow the requirements of this protocol. In 
case of need to modify this protocol, it can only be implemented after notification to the Fosun for 
agreement and the approval or filing agreement of the ethics committee, unless measures that must 
be taken to protect the safety, rights, and interests of the subjects. 
I will provide copies of this protocol to all the study personnel participating in this study under my 
responsibility, and discuss the protocol and related information with them to ensure that they fully 
understand the investigational vacccine and how to conduct this study. 
I will keep this protocol and related content confidential. 
 
 
  
 
 
 
 
Clinical study institution: Jiangsu Provincial Center for Disease Control and Prevention 
Principal investigator (printing): 
 
 
(Signature): _______________ Date of signature: ________ 
 
 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 4 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
TABLE OF CONTENTS  
1.0 
ADMINISTRATIVE INFORMATION ............................................................................... 2 
1.1 Contacts ............................................................................................................................... 2 
1.2 Document History ................................................................................................................ 2 
1.3 Approval .............................................................................................................................. 2 
TABLE OF CONTENTS ..................................................................................................... 4 
LIST OF IN-TEXT TABLES ............................................................................................... 8 
LIST OF IN-TEXT FIGURES ............................................................................................. 8 
2.0 
TRIAL SUMMARY ............................................................................................................ 9 
3.0 
LIST OF ABBREVIATIONS ............................................................................................ 32 
4.0 
INTRODUCTION ............................................................................................................. 34 
4.1 Background ........................................................................................................................ 34 
4.1.1 SARS-CoV-2 ............................................................................................................. 34 
4.1.2 Epidemiology ............................................................................................................ 34 
4.2 Rationale of trial plan ........................................................................................................ 35 
4.2.1 Medical need ............................................................................................................. 35 
4.2.2 RNA vaccines under development ............................................................................ 35 
4.2.3 Summary of available non-clinical data ................................................................... 36 
4.2.4 Summary of available clinical data ........................................................................... 40 
4.2.5 BioNTech RNA-based vaccine candidate ................................................................. 42 
4.2.6 Rationale for BNT162-03 trial .................................................................................. 43 
4.3 Benefit/risk assessment ...................................................................................................... 44 
4.3.1 Risk assessment ........................................................................................................ 44 
4.3.2 Benefit assessment .................................................................................................... 47 
4.3.3 Overall benefit/risk conclusion ................................................................................. 47 
5.0  
TRIAL OBJECTIVES AND ENDPOINTS....................................................................... 48 
5.1 Objectives .......................................................................................................................... 48 
5.1.1 Primary objective ...................................................................................................... 48 
5.1.2 Secondary objectives ................................................................................................ 48 
5.1.3 Exploratory objective ................................................................................................ 48 
5.2 Endpoints ........................................................................................................................... 48 
5.2.1 Primary endpoints ..................................................................................................... 48 
5.2.2 Secondary endpoints ................................................................................................. 49 
5.2.3 Exploratory endpoints ............................................................................................... 49 
6.0 TRIAL DESIGN AND DESCRIPTION .................................................................................. 50 
6.1 Overall trial design ............................................................................................................ 50 
6.2 Subjects enrollment and dose cohorts ............................................................................... 53 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 5 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
6.3 Dose modification .............................................................................................................. 53 
6.4 Justification for trial design, dose, and endpoints ............................................................. 53 
6.5 Duration of subject’s expected participation in the entire trial.......................................... 53 
6.6 Dose limiting toxicity (DLT) ............................................................................................. 54 
6.7 Criteria for delay of boost vaccination and/or stop for boost vaccination ......................... 54 
6.8 Criteria for early study termination of a subject ................................................................ 55 
6.9 Criteria for premature discontinuation of trial vaccine application ................................... 56 
6.10. Premature termination or suspension of the trial ............................................................ 58 
6.10.1 Criteria for premature termination or suspension of the trial ................................. 58 
6.10.2 Procedures for premature termination or suspension of the trial ............................ 58 
7.0 Inclusion and exclusion criteria ............................................................................................... 59 
7.1 Inclusion and exclusion criteria for adults ......................................................................... 59 
7.2 Inclusion and exclusion criteria for the elderly ................................................................. 61 
8.0 VACCINATION AND MANAGEMENT OF VACCINE ....................................................... 64 
8.1 Vaccination ........................................................................................................................ 64 
8.1.1 Investigational vaccine/ placebo ............................................................................... 64 
8.1.2 Preparation/handling/storage/accountability............................................................. 64 
8.1.3 Dose and regimen ..................................................................................................... 65 
8.2 Allocation, preparation and injection procedures of investigational vaccine/placebo ...... 65 
8.3 Randomization code creation and storage ......................................................................... 66 
8.4 Maintain of blinding .......................................................................................................... 66 
8.5 Unblinding procedures....................................................................................................... 66 
9.0 TRIAL PLAN .......................................................................................................................... 67 
9.1 Trial procedures ................................................................................................................. 67 
9.1.1 Informed consent ...................................................................................................... 67 
9.1.2 Demographics, medical history, travel history, prior/concomitant 
medications/vaccinations, and blood donation .................................................................. 67 
9.1.3 SARS-CoV-2 testing ................................................................................................. 68 
9.1.4 Physical examination ................................................................................................ 68 
9.1.5 Vital signs, 12-lead ECG and chest CT scan ............................................................ 69 
9.1.6 Blood sample and urine sample collection ............................................................... 69 
9.1.7 Safety assessments .................................................................................................... 71 
9.1.8 Contraception guidance ............................................................................................ 71 
9.1.9 Pregnancy .................................................................................................................. 71 
9.1.10 Documentation of trial entrance/randomization ..................................................... 72 
9.1.11 Documentation of subjects who are not enrolled/randomized ................................ 72 
9.2 Subject treatment compliance ............................................................................................ 73 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 6 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
9.3 Schedule of observations and procedures .......................................................................... 73 
9.3.1 Screening procedures (Screening Visit) .................................................................... 73 
9.3.2 Pre-vaccination procedures ....................................................................................... 74 
9.3.3 Vaccination procedures ............................................................................................. 74 
9.3.4 Post-vaccination procedures ..................................................................................... 74 
9.3.5 Main visits post vaccination...................................................................................... 76 
9.3.6 Follow-up extension.................................................................................................. 77 
9.4 Biological sample retention and destruction...................................................................... 77 
10.0 ADVERSE EVENTS ............................................................................................................. 78 
10.1 Definitions ....................................................................................................................... 78 
10.1.1 Adverse events (AEs) .............................................................................................. 78 
10.1.2 Solicited reactions ................................................................................................... 78 
10.1.3 Serious adverse events (SAEs) ............................................................................... 79 
10.1.4 Adverse events of special interest ........................................................................... 80 
10.1.5 AE associated with an overdose or error in vacccine administration ..................... 81 
10.2 Collection and record of safety events............................................................................. 81 
10.2.1 Collection and reporting of solicited reactions ....................................................... 81 
10.2.2 Collection and reporting of unsolicited reactions ................................................... 81 
10.2.3 Collection and reporting of SAEs ........................................................................... 82 
10.3 Assessment of safety parameters ..................................................................................... 82 
10.3.1 Assessment of intensity ........................................................................................... 82 
10.3.2 Relationship to investigational drug ....................................................................... 83 
10.3.3 Relationship to trial procedures .............................................................................. 84 
10.3.4 Expectation assessment of adverse events .............................................................. 84 
10.4 Follow-up of adverse events ............................................................................................ 84 
10.5 Treatment of reactions and adverse events ...................................................................... 85 
10.6 Outcome of adverse events .............................................................................................. 85 
11.0 Monitoring Committee .......................................................................................................... 87 
11.1 Safety Review Committee (SRC) .................................................................................... 87 
11.2 Independent Data Monitoring Committee (IDMC) ......................................................... 87 
12.0 DATA MANAGEMENT ....................................................................................................... 89 
12.1 Data collection and management ..................................................................................... 89 
12.2 Database lock ................................................................................................................... 89 
13.0 STATISTICAL METHODS................................................................................................... 90 
13.1 Statistical and analytical plans ......................................................................................... 90 
13.1.1 Analysis sets ............................................................................................................ 90 
13.1.2 General principles ................................................................................................... 90 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 7 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
13.1.3 Analysis of demographics and other baseline characteristics ................................. 91 
13.1.4 Primary endpoints ................................................................................................... 91 
13.1.5 Immunogenicity analysis ........................................................................................ 92 
13.1.6 Safety analysis ........................................................................................................ 92 
13.2 Periodical Analysis .......................................................................................................... 93 
13.3 Determination of sample size .......................................................................................... 93 
14.0 STUDY MANAGEMENT .................................................................................................... 94 
14.1 Ethical considerations ...................................................................................................... 94 
14.2 Informed consent ............................................................................................................. 94 
14.3 Protocol amendments ...................................................................................................... 95 
14.4 Protocol deviations .......................................................................................................... 95 
14.5 Subject confidentiality and privacy ................................................................................. 95 
14.6 Monitoring ....................................................................................................................... 96 
14.7 Quality assurance and quality control.............................................................................. 96 
14.8 Direct access .................................................................................................................... 97 
14.9 Data recording and storage .............................................................................................. 97 
14.10 Subject insurance and indemnity ................................................................................... 97 
14.11 Storage and use of biological specimens ....................................................................... 97 
14.12 Study interruption and early termination ....................................................................... 97 
14.13 Study summary report.................................................................................................... 98 
14.14 Information disclosure and data publishing policy ........................................................ 98 
Appendix A．WHO and CDC Website ......................................................................................... 99 
Appendix B NMPA Guidance for Adverse Events Grading Scale for Preventive Vaccine Clinical 
Trials in China ............................................................................................................................. 100 
Appendix C. FDA Toxicity Grading Scale in Preventive Vaccine Clinical Trials....................... 108 
Appendix D．Collection and Processing of Throat Swab Specimens ........................................ 111 
15.0 
References ........................................................................................................................ 112 
 
 
 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 8 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
LIST OF IN-TEXT TABLES  
Table 1  Contact information ................................................................................................... 2 
Table 2  Schedule of activities ............................................................................................... 23 
Table 4  Clinical laboratory assessments ............................................................................... 70 
Table 5  Solicited local and systemic reactions ..................................................................... 78 
Table 6 Contact information for serious adverse events reporting ........................................ 82 
 
LIST OF IN-TEXT FIGURES   
Figure 1 Schematic diagram of two-dose parallel design ...................................................... 12 
Figure 2  Anti-S IgG response 7, 14, 21 and 28 days after immunization with BNT162b1 .. 37 
Figure 3  Kinetics of the antibody concentration against the viral antigen ........................... 38 
Figure 4  Neutralization of SARS CoV-2 pseudovirus 14, 21 and 28 d after immunization 
with BNT162b1 ............................................................................................................. 39 
Figure 5 Overall study design: adult subjects (above) and elderly subjects (below) ............. 51 
 
 
 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 9 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
2.0 
TRIAL SUMMARY  
BioNTech RNA Pharmaceuticals GmbH 
An der Goldgrube 12, 
55131 Mainz, Germany 
Product Name:  
SARS-CoV-2 mRNA Vaccine (BNT162b1)  
Trial Title: Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine (BNT162b1) in Chinese Healthy 
Subjects: A Phase I, Randomized, Placebo-controlled, Observer-blind Study 
IND No.: 2020L00032/ 2020L00033  
EudraCT No.: NA  
Study Identifier: BNT162-03  
Phase: I  
Trial Blinding Schema: Observer-blind 
Background and Rationale:  
SARS-CoV-2 is a single-stranded positive-sense ribonucleic acid (RNA) virus which belongs to the coronavirus 
family that presents about 78% of structural similarities with other members of the coronavirus, including SARS 
virus. Coronaviruses are a large family of viruses that are common in many different species of animals, including 
camels, cattle, cats, and bats. It is rarely for animal coronaviruses to infect people and then spread among infected 
people just like SARS-CoV-2.[1] 
SARS-CoV-2 was discovered in January 2020 in Wuhan. The first human disease cases were reported in 
December 2019 in China. The virus circulated in areas of over 200 countries worldwide, and was considered 
Acute Respiratory disease syndrome (COVID-19) with mild to severe symptoms. The primary mode of 
transmission of SARS-CoV-2 is person-to-person contact through respiratory droplets. Patients with mild or 
asymptomatic infections may account for 60% of all infected patients. Some clinical manifestations include, but 
are not limited to, fever, cough, and diarrhea. [2, 3] 
Despite mild clinical symptoms in most adults, SARS-CoV-2 infection over 65 years old has been associated 
with serious outcomes. The severity of the disease is related to the attacks of autoimmunity on pulmonary alveoli. 
Since the beginning of these outbreaks and up to mid-May 2020, there has been more than 4,580,000 confirmed 
COVID-19 associated with SARS-CoV-2 infection with over 310,000 deaths in over 200 countries, areas, or 
territories worldwide. [4]  
SARS-CoV-2 is a respiratory virus that can cause disease of the respiratory system. The overall incidence of 
SARS-CoV-2-associated COVID-19 is unknown currently. In the epidemic curve up to January 4, 2020, the 
epidemic growth rate was 0.10 per day (95% CI, 0.050 to 0.16) and the doubling time was 7.4 days (95% CI, 4.2 
to 14). Using the serial interval distribution above, we estimated that R0 was 2.2 (95% CI, 1.4 to 3.9) [3].  
No specific antiviral treatment is available for SARS-CoV-2 infections and no vaccine against SARS-CoV-2 is 
currently available. As the disease is self-limiting, treatment for uncomplicated COVID-19 infection is supportive 
and focuses on symptoms. The main recommendations to prevent outbreaks are through social distancing 
(avoiding person-to-person contact transmission), and personal protective equipment (PPE) measures. 
The risk of infection with SARS-CoV-2 is increasing given that the spread of SARS-CoV-2 is rapid and intense 
in over 200 countries, areas, or territories. SARS-CoV-2 has posed a challenging situation for health, public and 
economic sectors of affected countries. 
The World Health Organization (WHO) declared on 30 January 2020 the SARS-CoV-2 outbreak as a Public 
Health Emergency of International Concern (PHEIC) and recommended to focus the research on the causal 
association of SARS-CoV-2 infection. Considering the spread to more new countries, this novel coronavirus 
disease COVID-19 outbreak was assessed as very high of global risk level on February 28 2020, and was declared 
as a pandemic by the WHO on March 11 2020. Considering the conclusive associations between SARS-CoV-2 
infections and severe acute respiratory syndrome, the development of a vaccine that can provide protection is 
crucial for countries where the epidemic is expected to arrive and/or persist, as well as in countries in which the 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 10 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
virus has not yet been epidemic. In order to address the urgent medical need and in anticipation of possible 
outbreaks with rapid onsets, the sponsor has initiated the development of a SARS-CoV-2 mRNA vaccine 
(BNT162b1), for use in endemic areas and non-endemic areas for prevention of SARS-CoV-2 associated illness 
of any severity and/or infection.  
The urgent engagement in the efforts to investigate, make available safe and effective SARS-CoV-2 interventions 
are needed to assist in the control of the outbreak. Given the severity of the situation, time to vaccine development 
was an important aspect of the highly unmet needs. In response to this need, an accelerated vaccine development 
effort was initiated. 
Two Phase I/II clinical studies of BNT162b1 are currently being conducted in Germany and the United States; at 
the same time, the immunogenicity, repeated dose toxicology study and viral challenge study are conducted in 
BALB/c mice in accordance with Good Laboratory Practice (GLP) to continuously analyze the efficacy and 
safety of BNT162b1 at animal level and human body level. Interim Report of the United States Phase I/II clinical 
study has been published. Results of data analyses for pre-clinical studies and clinical studies will be provided 
by continuously updating in the Investigator's Brochure (IB). The clinical studies conducted in Germany and the 
United States are first-in-human trials, so dose escalation mode is adopted and sentinel subjects are added for 
both. The maximum dose examined in these two studies is 100µg, and the safety result shows that the local 
reaction of vaccination site and systemic event are dose-dependent which is mostly mild to moderate with short 
duration, reactions after two vaccinations are similar, and reaction is slightly less in elderly group; 
immunogenicity result shows that serum RBD specific IgG antibody concentration and SARS-CoV-2 neutralizing 
antibody titer escalate with dose level and increase after booster vaccination. The geometric mean neutralizing 
titer is 1.8 to 2.8 times that of a group of COVID-19 human serum during recovery period. Above results will 
support the further evaluation of the mRNA candidate vaccine. Currently, the optimal dose range is predicted as 
10~30 µg according to safety and efficacy data of foreign subjects. Since the preliminary safety and immunology 
data are obtained, and clinical studies conducted in Germany and the United States will continue to support 
studies in China, so China plans to conduct bridging trial to confirm foreign study results among Chinese subjects. 
BNT162-03 is a phase I, dose confirmation study in China, which adopts a parallel two-dose cohort design in 
adult healthy subjects (adult group) and elderly healthy subjects (senior group); and the trial in adult group is 
conducted firstly and followed by the trial in the elderly group. And the study is intended to confirm that the 
response (safety/immunogenicity) seen in foreign subjects is comparable to that in Chinese subjects. Healthy 
adults who are ≥18 years old and ≤55 years old will be enrolled in the adult group and healthy elderly subjects 
who are ≥65 years old and ≤85 years old will be enrolled in the elderly group. To ensure the enrollment of healthy 
subjects, screening tests (hematology, biochemistry, and urinalysis) will be performed prior to vaccine/placebo 
vaccination. In each age group of subjects, the trial will be conducted by the parallel two-dose and placebo cohort 
allocation. The design of this study, including the selection of two optimal dose levels referred to the safety and 
immunogenicity data from the ongoing or completed foreign studies of BNT162b1. In this study, a Safety Review 
Committee (SRC) will be comprised of investigators, Fosun medical representative and medical monitor, and 
SRC will review the safety data in a blinded manner. SRC will review the available safety and tolerability data 
of all subjects in a dose cohort (including at least safety laboratory test results and safety events collected from 
diary cards within 14 days after the prime vaccination) before starting the boost vaccination for each cohort to 
suggest whether the boost vaccination of BNT162b1 vaccine can be conducted. The study will also set up an 
Independent Data Monitoring Committee (IDMC) to conduct overall supervision. The IDMC is required to 
review the unblinded data when a significant event or risk occurs in the study that might cause the study to be 
suspended.  
Due to the ongoing threat of SARS-CoV-2 disease and the urgent need of a vaccine, this study will be accelerated 
to assess the bridging data for BNT162b1, in addition to confirm that the response (safety/immunogenicity) seen 
in foreign subjects is comparable to that observed in Chinese subjects. 
Placebo serves as the control for the study vaccine and in the absence of effective treatment or prevention for 
COVID-19, the use of placebo in this trial is justified. Based on the different physical appearance of the 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 11 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
investigational vaccine compared to the saline solution placebo that will be selected, an independent non-blind 
team is adopted in this study for blinding subjects and observers. 
All enrolled subjects will receive two doses of either SARS-CoV-2 vaccine (BNT162b1) or placebo 
intramuscularly (IM) on Day 1 and on Day 22. The objective of the study BNT162-03 is to assess the safety and 
immunogenicity of BNT162b1 in the Chinese healthy subjects. 
The primary rationale for selection of the vaccine dose levels can be summarized as follows: 
Based on the clinical data from the overseas clinical studies, and the non-clinical data of the RNA components 
(modRNA), with other liposomes or in conjunction with the lipid nanoparticles as will be tested clinically in this 
trial, we expect that doses in the 1 to 5 μg range will be immunogenic and induce neutralizing antibodies. The 
dose range of 1~100 µg has been identified in foreign subjects, based on safety and efficacy data. Accordingly, a 
degree of reactogenicity is anticipated with BNT162b1 with mild or moderate local or systemic reactions 
common amongst subjects.  
Two predicted optimal doses are selected according to the safety and immunogenicity data of global clinical trials 
in Germany and the United States as available at present to confirm the comparability of safety and efficacy for 
BNT162b1 in China.  
• 
The low-dose level (10 µg);  
• 
The high-dose level (30 µg);  
The trial will be conducted in accordance with the protocol, the International Council for Harmonization of 
Technical Requirements for Pharmaceuticals (ICH) GCP Guidelines and applicable regulatory requirements. 
 
Trial Design:  
This is a phase I, randomized, placebo-controlled, observer-blind, safety and immunogenicity study of SARS-
CoV-2 mRNA vaccine (BNT162b1) in Chinese healthy subjects. After randomization, the trial for each subject 
will last for approximately 12 months. Screening period is 2 weeks prior to randomization (Day -14 to Day 0), 
and each dose of either SARS-CoV-2 vaccine (BNT162b1) or placebo will be given intramuscularly (IM) on Day 
1 and on Day 22. After each age group completes the follow-up 28 days after boost vaccination (Day 50), initial 
analysis will be conducted.  
Subjects who are ≥18 years old and ≤ 55 years old will be enrolled in adult group, and healthy elderly subjects 
who are ≥65 years old and ≤85 years old will be enrolled in elderly group. Approximately 72 subjects for each 
age group will be allocated to three cohorts (BNT162b1 high-, low-dose groups and placebo group) in parallel, 
with approximately 24 subjects at each BNT162b1 dose level, including 24 placebo group subjects, the subjects 
will be randomized in a 1:1:1 ratio. 
After the 14-day safety observation post the prime vaccination of the subjects in adult group, the prime 
vaccination for the subjects in the elderly group will start. SRC will review the available safety and tolerability 
data of all subjects in a cohort (including safety observation 14 days after the prime vaccination for all subjects 
in this cohort) before starting the boost vaccination for each cohort, to decide whether the BNT162b1 vaccine 
can be boosted. 
For dose allocation design, see schematic diagram in Figure 1. For the planned assessments and visits, see 
schedule of activities in Table 2. 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 12 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
 
Figure 1 Schematic diagram of dose parallel design 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 13 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
 Subjects enrollment and dose cohorts: 
The study will be aimed at enrolling SARS-CoV-2 naïve subjects. All subjects who sign the informed consent 
form (ICF) and have confirmed basic eligibility at Screening will be tested for SARS-CoV-2 antibodies 
(qualitative), virus nucleic acid and chest computed tomography (CT). Within 2 weeks after the screening visit, 
naïve subjects selected in each cohort at Screening will be randomized at visit 1.  
The study will follow a parallel dose cohort design, as shown in Figure 1.   
The enrollment process of subjects in adult group is as follows: 
• 
The planned low-dose cohort, high-dose cohort and placebo group. 72 subjects will be randomized in a 1:1:1 
ratio to inject BNT162b1 or placebo on Day 1.   
• 
If the SRC considers that the subjects are safe with good tolerance after 14 days of observation, boost 
vaccination will be conducted on Day 22.   
• 
When the subjects in the adult group completed safety visits up to 14 days post prime vaccination, the 
available safety data for all subjects were summarized. If approved by the SRC,   
o 
The planned dose cohorts of elderly group will be initiated (see Figure 1).   
The data assessed by the SRC comprises: vital signs, TEAEs, local reactions, blood/clinical laboratory 
data and brief physical examination outcome.   
o 
The parallel dose cohort study is conducted in the elderly group with consistent methods as those in the 
adult group (see Figure 1).  
Vaccination protocol and visit schedule 
Each randomized subject will be given two doses of either BNT162b1 (10 or 30 µg) or placebo intramuscularly 
(IM) – one vaccination at Visit 1 (on Day 1) and one vaccination at Visit 5 (on Day 22), into one third of the 
deltoid muscle, preferably in the non-dominant arm.  
From the treatment randomization, each subject will be required to attend 12 clinical visits:  
All immunized subjects will attend Visit 1 (prime vaccination) on Day 1, Visit 2 on Day 2 (24 hours after prime 
vaccination), Visit 3 on Day 8 (7 days after prime vaccination), Visit 4 on Day 15 (14 days after prime 
vaccination), Visit 5 on Day 22 (boost vaccination), Visit 6 on Day 29 (7 days after boost vaccination), Visit 7 on 
Day 36 (14 days after boost vaccination), Visit 8 on Day 43 (21 days after boost vaccination), Visit 9 on Day 50 
(28 days after boost vaccination), Visit 10 at Month 3, Visit 11 at Month 6 and Visit 12 at Month 12.  
Blood samples of subjects in adult group will be collected at the following visits for different tests: at Screening 
Visit (Visit 0) for eligibility screening tests (including clinical laboratory), at Visits 2, 3, 6 for routine safety 
laboratory testing (visits 2, 6 coagulation function test, visit 2, 6, 11 thyroid function test), at Visit 1 (prior to 
prime vaccination) and Visits 5 (prior to boost vaccination), 6, 8, 10, 11, 12 for humoral immunity (antibody). 
Blood sample will be collected at Visit 1 (prior to prime vaccination) and Visits 6, 8, 11 for cell-mediated 
immunity (CMI). Urine samples will be collected at Screening Visit (Visit 0) for eligibility screening and 
collected at Visits 2, 3, 6 for regular safety laboratory testing; serum samples of women of childbearing potential 
will be collected at Screening Visits (Visit 0) and Visit 5 (prior to boost vaccination) for pregnancy test. Fingertip 
blood will be collected during the screening visit (visit 0) for detection of SARS-CoV-2 antibody and HIV 
antibody. 
Blood samples of subjects in elderly group will be collected at the following site visit for different tests: at 
Screening Visit (Visit 0) for eligibility screening tests (including clinical laboratory), at Visits 2, 3, 6 for regular 
safety laboratory testing, at Visit 1 (prior to prime vaccination) and Visit 5 (prior to boost vaccination), 6, 8, 11, 
12 for humoral immunity (antibody). Blood sample will be collected at Visit 1 (prior to prime vaccination) and 
Visit 6 for cell-mediated immunity (CMI). Urine samples will be collected at Screening Visit (Visit 0) for 
eligibility screening and collected at Visits 2, 3, 6 for regular safety laboratory testing; serum samples of women 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 14 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
of childbearing potential will be collected at Screening Visits (Visit 0) and Visit 5 for pregnancy test. Fingertip 
blood will be collected during the screening visit (visit 0) for detection of SARS-CoV-2 antibody and HIV 
antibody. 
Each subject will receive diary cards to collect solicited reaction for 14 days after each vaccination (including 
the days of vaccine/placebo vaccination), and unsolicited AE for 21 days after prime vaccination and 28 days 
after boost vaccination (including the days of vaccine/placebo vaccination). Additional safety assessments will 
include vaccine related adverse events (AEs) collection for the rest of the entire trial. 
Primary objective  
• 
To evaluate the safety and tolerability profiles of BNT162b1 prime/boost (P/B) immunization given 21 days 
apart from different doses in SARS-CoV-2 naïve Chinese healthy subjects through 28 days after boost 
vaccination.   
Secondary objectives   
• 
To observe the immunogenicity (anti-S1 and anti-RBD IgG antibody) of two doses of BNT162b1 given 21 
days apart measured by enzyme-linked immunosorbent assay (ELISA). 
• 
To observe the immunoreactivity of healthy subjects after BNT162b1 P/B immunization by the true virus-
based SARS-CoV-2 neutralizing antibody assay. 
• 
To observe the safety of BNT162b1 vaccination in Chinese healthy subjects until the end of the study.  
• 
To conduct 12-month follow-up for healthy subjects in the BNT162b1 vaccination dose cohorts, and observe 
the sustainability of the immune response to BNT162b1. 
Exploratory objective    
 
 
 
 
 
 
 
 
 
Subject subjects:  
Healthy subjects: SARS-CoV-2 naïve  
Planned age range: Adults (age ≥18 and ≤55 years old) and elderly (age ≥65 years old and ≤85 years old)   
Planned subjects: a total of 144 subjects will be randomized, including approximately 72 in each of 2 age groups 
(including 2 dose cohorts and 1 placobo group, 24 in each group).  
Planned number of cohorts: 
Subjects will be allocated to receive 2 BNT162b1 dose cohorts or placebo group (in each group: n=24 subjects). 
• 
Cohort 1: BNT162b1 low-dose; 
• 
Cohort 2: BNT162b1 high-dose; 
• 
Cohort 3: placebo. 
For adult subjects (age ≥18 and ≤55) 
Inclusion criteria:  
1. 
Male or female subjects of ≥18 years old and ≤55 years old with body mass index (BMI) ≥18 and ≤30 
at the Screening Visit.   

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 15 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
2. 
Individuals who are in good health condition at the time of entry into the trial as determined by medical 
history, physical examination (including vital signs, ECG) and eligibility screening test (hematology, 
blood chemistry and urine analysis) and clinical judgment of the investigator at Screening Visit.   
3. 
The subject can provide with informed consent and signs and dates a written informed consent form (ICF) 
prior to the initiation of any trial procedures. 
4. 
They must be able to understand and follow trial-related instructions.  
5. 
They must be willing and able to comply with planned visits, treatment schedule, laboratory tests and 
other requirements of the trial.  
6. 
Negative in antibodies screening of SARS-CoV-2 (fingerstick). 
7. 
Normal in chest CT scans (no imaging features of COVID-19). 
8. 
Axillary temperature≤37.0ºC. 
9. 
Negative SARS-CoV-2 test in throat swabs by RT-PCR. 
10. Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-
hCG) in serum sample at Screening Visit. Women that are postmenopausal (Menopause≥12 consecutive 
months) or permanently sterilized will be considered as not having reproductive potential.  
11. WOCBP must have used effective contraception 14 days prior to screening and agree to use effective 
contraception continuously during the trial period, from 14 days prior to Screening Visit to 60 days after 
the last immunization.  
12. WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during 
trial, starting from Screening Visit and continuously until 60 days after be given the last immunization.  
13. Men who are sexually active with a WOCBP and have not had a vasectomy must agree to practice a 
effective form of contraception with their female partner of childbearing potential during the trial, starting 
from Screening Visit and continuously until 60 days after be given the last immunization.  
14. Men must be willing to refrain from sperm donation, starting from Screening Visit and continuously until 
60 days after receiving the last immunization.  
Exclusion criteria:    
1. Have had any acute illness, as determined by the investigator, with or without fever, within 72 h prior to the 
prime vaccination. 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.  
2. Are breastfeeding on the day of Screening Visit or who plan to breastfeed during the trial, starting from 
Screening Visit and continuously until at least 90 days after the last immunization. Women or partners who 
plan to become pregnant within 1 year post the screening visit.  
3. Have a known allergy, hypersensitivity, or intolerance to the planned vaccine for trial including any 
excipients.  
4. Used to have a history of hypersensitivity or serious reactions to vaccination. 
5. Received any vaccination within 4 weeks prior to Visit 1.  
6. Don't agree to not be vaccinated during the trial, starting from Screening Visit and continuously until 28 days 
after receiving the last immunization, except emergency vaccination (e.g. rabies vaccine, tetanus vaccine). 
7. Had any medical condition (e.g., autoimmune disease) or any major surgery (e.g., requiring general 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 16 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
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.  
8. Have any surgery planned during the trial, starting from Screening Visit and continuously until at least 90 
days after the last immunization.  
9. Had any chronic use (more than 14 continuous days) of any systemic medications that affects immune 
function, including immunosuppressant or other immune-modifying drugs, within 6 months prior to 
Screening Visit unless in the opinion of the investigator, the medication would not prevent, limit, or confound 
the protocol-specified assessments or could compromise safety of subjects.  
10. Had administration of any immunoglobulins and/or any blood products within the 3 months prior to 
Screening Visit.  
11. Had administration of another investigational product including vaccines within 60 days or 5 half-lives 
(whichever is longer), prior to Screening Visit.  
12. With known history of AIDS or HIV test positive.  
13. History of HBV or HCV infection, through medical inquiry.  
14. History of SARS, SARS-CoV-2 or MERS infection. Suspected SARS patients should be screened for SARS 
antibodies. 
15. Previously participated in a clinical trial involving lipid nanoparticles.  
16. Are subject to exclusion periods of other clinical trials or simultaneous participation in another clinical trial. 
17. Have any affiliation with the study site (e.g., are close relative of the investigator or dependent person, such 
as an employee or student of the study site).  
18. Have a history of drug abuse or known medical, psychological, or social conditions within the past 5 years. 
In the opinion of the investigator, could comprise their well-being if they participate as trial subjects in the 
trial, or that could prevent, limit, or confound the protocol-specified assessments.  
19. Have a history of narcolepsy.  
20. Have history of alcohol abuse or drug addiction within 1 year prior to Screening Visit.  
21. Have a history of or suspected immunosuppressive condition, acquired or congenital, as determined by 
medical history and/or physical examination at Screening Visit.  
22. Have any abnormality or permanent body art (e.g., tattoo), in the opinion of the investigator, would obstruct 
the ability to observe local reactions at the vaccination site.  
23. Have had any blood loss >400 mL, e.g., due to donation of blood or blood products or injury, within the 28 
days prior to Screening Visit or plan to donate blood or plasma during the trial, starting from Screening Visit 
and continuously until at least 28 days after be given the last immunization.  
24. Travel or live in any country or region with a high SARS-CoV-2 infection risk (as defined at Screening Visit) 
within the 14 days prior to Screening Visit.  
25. They plan to visit any country or region with a high SARS-CoV-2 infection risk (as defined at Screening 
Visit), from Screening Visit until 14 days after be given the last immunization.  
26. Symptoms of COVID-19, e.g., respiratory symptoms, fever, cough, shortness of breath and breathing 
difficulties.  
27. Have had contact with confirmed COVID-19 patients or persons tested positive for SARS-CoV-2 within the 
30 days prior to Screening Visit.  

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 17 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
28. Are vulnerable persons, e.g., soldiers, subjects in detention, CRO or Fosun staffs or their family members. 
For the elderly subjects (age ≥65 years old and ≤85 years old) 
Inclusion criteria: 
1. Male or female subjects ≥65 years old and ≤85 years old at Screening Visit.   
2. Individuals who are in a health condition that can receive the investigational vaccine, at the time of entry into 
the trial as determined by medical history, physical examination (including vital signs, ECG) and eligibility 
screening tests (hematology, biochemistry and urinalysis) and clinical judgment of the investigator at 
Screening Visit.   
3. The subject can provide with informed consent and signs and dates a written informed consent form (ICF) 
prior to the initiation of any trial procedures. 
4. They must be able to understand and follow trial-related instructions.  
5. They must be willing and able to comply with planned visits, treatment schedule, laboratory tests and other 
requirements of the trial.  
6. Negative in antibodies screening of SARS-CoV-2 (blood samples from fingertip). 
7. No imaging features of COVID-19 in chest CT. 
8. Axillary temperature≤37.0ºC. 
9. Negative SARS-CoV-2 test in throat swabs by RT-PCR. 
10. Women of childbearing potential (WOCBP) must have a negative serum β-hCG at Screening Visit. Women 
that are postmenopausal (Menopause≥12 consecutive months) or permanently sterilized will be considered 
as not having reproductive potential.  
11. WOCBP must have used effective contraception 14 days prior to screening and agree to use effective 
contraception continuously during the trial period, from 14 days prior to Screening Visit to 60 days after the 
last immunization.  
12. WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, 
starting from Screening Visit and continuously until 60 days after be given the last immunization.  
13. Men who are sexually active with a WOCBP and have not had a vasectomy must agree to practice a effective 
form of contraception with their female partner of childbearing potential during the trial, starting from 
Screening Visit and continuously until 60 days after be given the last immunization.  
14. Men must be willing to refrain from sperm donation, starting from Screening Visit and continuously until 60 
days after receiving the last immunization.  
Exclusion criteria:    
1. Baseline laboratory abnormalities with Grade ≥3 (for hematology abnormalities with Grade ≥2, according 
to the grading criteria in appendix B) during screening visits, by physical examination and eligibility 
screening. 
2. Have had any acute illness, as determined by the investigator, with or without fever, within 72 h prior to the 
prime vaccination. 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 will not prevent, limit, or confound the protocol-specified 
assessments.  
3. Have a known allergy, hypersensitivity, or intolerance to the planned vaccine for trial including any 
excipients.  

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 18 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
4. Used to have a history of hypersensitivity or serious reactions to vaccination. 
5. Received any vaccination within 4 weeks prior to Visit 1. 
6. Don't agree to not be vaccinated during the trial, starting from Screening Visit and continuously until 28 days 
after receiving the last immunization, except emergency vaccination (e.g. rabies vaccine, tetanus vaccine). 
7. Had administration of any immunoglobulins and/or any blood products within the 3 months prior to 
Screening Visit. 
8. Had any serious or life-threatening medical condition (e.g., autoimmune disease, cardiovascular disease) 
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.  
9. Have any surgery planned during the trial, starting from Screening Visit and continuously until at least 90 
days after the last immunization.  
10. Had any chronic use (more than 14 continuous days) of any systemic medications that affects immune 
function, including immunosuppressant or other immune-modifying drugs, within 6 months prior to 
Screening Visit unless in the opinion of the investigator, the medication would not prevent, limit, or confound 
the protocol-specified assessments or could compromise safety of subjects.  
11. Had administration of another investigational product including vaccines within 60 days or 5 half-lives 
(whichever is longer), prior to Screening Visit.  
12. With known history of AIDS or HIV test positive.  
13. History of HBV or HCV infection.  
14. History of SARS, SARS-CoV-2 or MERS infection. Suspected SARS patients should be screened for SARS 
antibodies. 
15. Previously participated in a clinical trial involving lipid nanoparticles.  
16. Are subject to exclusion periods of other clinical trials or simultaneous participation in another clinical trial. 
17. Have any affiliation with the study site (e.g., are close relative of the investigator or dependent person, such 
as an employee or student of the study site).  
18. Have a history of drug abuse or known medical, psychological, or social conditions within the past 5 years. 
In the opinion of the investigator, could comprise their well-being if they participate as trial subjects in the 
trial, or that could prevent, limit, or confound the protocol-specified assessments.  
19. Have a history of narcolepsy.  
20. Have history of alcohol abuse or drug addiction within 1 year prior to Screening Visit. 
21. Have a history of or suspected immunosuppressive condition, acquired or congenital, as determined by 
medical history and/or physical examination at Screening Visit.  
22. Have any abnormality or permanent body art (e.g., tattoo), in the opinion of the investigator, would obstruct 
the ability to observe local reactions at the vaccination site.  
23. Have had any blood loss >400 mL, e.g., due to donation of blood or blood products or injury, within the 28 
days prior to Screening Visit or plan to donate blood or plasma during the trial, starting from Screening Visit 
and continuously until at least 28 days after be given the last immunization. 
24. Travel or live in any country or region with a high SARS-CoV-2 infection risk (as defined at Screening Visit) 
within the 14 days prior to Screening Visit.  
25. They plan to visit any country or region with a high SARS-CoV-2 infection risk (as defined at Screening 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 19 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
Visit), from Screening Visit until 14 days after be given the last immunization.  
26. Symptoms of COVID-19, e.g., respiratory symptoms, fever, cough, shortness of breath and breathing 
difficulties.  
27. Have had contact with confirmed COVID-19 patients or persons tested positive for SARS-CoV-2 within the 
30 days prior to Screening Visit. 
28. Are vulnerable persons, e.g., soldiers, subjects in detention, CRO or Fosun staffs or their family members. 
Trial Vaccines:  
Investigational Vaccine:  
The drug product is a preservative-free, sterile dispersion of RNA formulated in lipid nanoparticles (LNP) in 
aqueous cryoprotectant buffer for intramuscular administration. The RNA drug substance is the only active 
ingredient in the drug product. The composition meets the supplier's specifications. For dispensing and operation 
protocol, see Pharmacy Manual. 
Frequency of 
vaccination:  
Two injections (21 days apart).  
Route of 
vaccination:  
Intramuscular (IM); upper arm, musculus deltoideus; the P/B regimens. The same 
arm may be used for both immunizations. The non-dominant arm is preferred.  
Placebo:  
NaCl 0.9% solution is being used as placebo. It is a sterile, clear, colorless liquid solution of sodium chloride 
without preservative designed for parenteral use only. Placebos are commercially packaged and stored according 
to the labeling. The placebo is vaccinated by IM at 21-day intervals.  
Duration of the trial/Evaluation period:  
Approximately 12 months (after screening period). 
Primary endpoints 
Safety and tolerability of BNT162b1, as determined by:  
• 
Occurrence of solicited local reactions in the subjects (eg, vaccination sites: pain/tenderness, 
erythema/redness, induration/swelling) during the 14-day after each dose of BNT162b1 or placebo.   
• 
Occurrence of solicited systematic reactions (eg, nausea, vomiting, diarrhea, headache, fatigue, myalgia, 
arthralgia, chills, loss of appetite, malaise and fever) during 14-day after each dose of BNT162b1 or placebo. 
• 
Occurrence of AE associated with vaccination in subjects during the 21-day period after prime vaccination 
and the 28-day period after boost dose of BNT162b1 or placebo.  
Secondary endpoints 
Safety and tolerability of BNT162b1, as determined by:  
• 
The proportion of subjects experiencing SAEs, occuring up to Day 21 after prime vaccination and Day 28 
after boost vaccination, up to Month 3, 6 and 12.  
• 
The proportion of subjects experiencing AE associated with BNT162b1, occuring up to Month 3, 6 and 12. 
• 
The proportion of of subjects experiencing abnormal markers of hematology, blood chemistry and urine 
analysis, occuring at Hour 24 and Day 7 after prime vaccination and at Day 7 after boost dose of BNT162b1 
or placebo.   
Immunogenicity of BNT162b1, as determined by: 
• 
Geometric mean titer (GMT) of anti-S1 IgG antibody at Day 7, Day 21 after prime vaccination, at Day 7, 
Day 21 after boost vaccination, and at Month 3, 6 and 12.   

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 20 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
• 
Geometric mean titer (GMT) of anti-RBD IgG antibody at Day 7, Day 21 after prime vaccination, at Day 7, 
Day 21 after boost vaccination, and at Month 3, 6 and 12.   
• 
GMT of SARS-CoV-2 neutralizing antibody (including true virus-based SARS-CoV-2 neutralizing antibody 
assay) at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 
and 12.  
• 
Fold increase in antibody anti-S1 IgG antibody titers, as compared to baseline, at Day 7, Day 21 after prime 
vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12. 
• 
Fold increase in antibody anti-RBD IgG antibody titers, as compared to baseline, at Day 7, Day 21 after 
prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12. 
• 
Fold increase in SARS-CoV-2 neutralizing antibody titers (virus neutralizing test), as compared to baseline, 
at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 
12. 
• 
Seroconversion rates (SCR), defined as a minimum of 4-fold increase of antibody titers, as compared to 
baseline, at Day 7, Day 21 after prime vaccination, and at Day 7, Day 21 after boost vaccination.  
Exploratory endpoints 
• 
 
 
 
 
 
 
 
 
 
 
 
Statistical Considerations:  
Analysis sets:  
• 
Safety Set: Safety Set will consist of all randomized subjects who receive at least one dose of the 
investigational vaccine/placebo and at least one safety evaluation.   
• 
Total Vaccinated Cohort (TVC): According to intention-to-treat analysis set principle, the TCV will include 
all randomized subjects who have received at least one dose of the investigational vaccine/placebo and 
provided valid baseline.  
• 
Per protocol set (PPS): The PPS will include all subjects in the TVC who have no major protocol violations 
and complete boost vaccination. The protocol violation criteria will be defined as part of the blinded data 
review. The categories of major protocol violations include:   
1 
not meeting inclusion criteria, or meeting exclusion criteria,  
2 
receiving a wrong investigational vaccine/placebo,   
3 
receiving prohibited therapies,  
4 
other major protocol violations that be identified during blinded data reviews.  
All summaries and analyses of safety data will be based on subjects in the Safety Set.   
The primary immunogenicity endpoint analyses will be based on the PPS and TVC, and additional 
immunogenicity endpoint analyses will be based on the TVC.  
Demographics and other baseline characteristic analysis: Summaries of age, gender, race, and other baseline 
characteristics will be presented by groups of BNT162b1 and placebo.  

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 21 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
Immunogenicity analysis: Descriptive statistics for the primary and secondary immunogenicity endpoints, 
including estimates and 95% confidence intervals (95% CI) for GMT and SCR, will be provided by time point 
and by different age’s groups, different dose cohorts of BNT162b1 and placebo group. Different BNT162b1 dose 
cohorts will be compared in pairs, and the GMT ratio of each two dose cohorts as well as the point estimate value 
of SCR difference and 95% CI will be calculated. Generally, immunogenicity will be summarized and analyzed 
based on age groups and dose cohorts.   
• 
Seronegative subjects: subjects with no detectable serum antibodies (test results are below Lower Limit of 
Detection) as measured by ELISA/neutralization assay.   
• 
Seroconverted subjects: By ELISA/neutralization detection, the subject whose serum antibodies titers after 
vaccination of subjects are at least 4 times higher than baseline. If the baseline did not reach the lower limit 
of titer detection, the positive conversion is defined as the antibody titer reaching at least 4 times of the lower 
limit. 
Safety analysis: Within 14 days after each vaccination (Including the day of vaccination of vaccine/placebo), 
by collecting soliciting AE, including local reactions (Vaccination site: pain/tenderness, erythema/redness, 
induration/swelling) and general reactions (nausea, vomiting, diarrhea, headache, fatigue/tiredness, myalgia, 
arthralgia, chills loss of appetite, malaise and fever), to evaluate reactogenicity. In addition, body temperature 
(axillary) as indicator of reactogenicity will be collected (with fever defined as axillary temperature ≥37.3ºC, 
oral temperature ≥38.0 ºC).  
For each solicited reaction, including fever, the percentage of subjects will be summarized by event severity for 
each day within 14 days after each vaccine/placebo vaccination and overall.  
All AEs and SAEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA version 23.0) 
and summarized by system organ class (SOC) and preferred term (PT) for each group (BNT162b1 and placebo) 
including aggravation after vaccination and new medical conditions.  
Safety summaries will be provided by different age groups and different dose cohorts/placebo groups. 
 
Sample Size Justification:  
This study is a phase 1 exploratory clinical trial.  
In the study, approximately 24 subjects will be included in each dose cohort of each age group, another 24 subjects 
vaccinated with placebo. If the occurrence of TEAE is 8%, the probability of observation of at least one TEAE 
in 24 subjects in each dose group is 86.5%, which is sufficient to perform safety evaluation for investigational 
vaccine at each dose level. 
 
Timepoint of Statistical Analysis:  
Initial analysis: 
In the study, all available safety and immunogenicity data will be included when all subjects in each age group 
complete Visit 9 (Day 50, 28 days after boost vaccination) to perform initial analysis. When all subjects in each 
age group complete Visit 11 (visit at Month 6 after prime vaccination), Viisit 12 (visit at Month 12 after prime 
vaccination), and an overall analysis will be performed.   
Unblinding will be occurred at the initial analysis of safety and immunogenicity 28 days after boost inoculation, 
but the subjects will be kept blinded. More details regarding the analyses will be provided in the Statistical 
Analysis Plan (SAP).  
The analysis report will be prepared after each phase of analysis and the overall study report will be prepared at 
the end of study.   

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 22 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
Confidential  
Safety Review Committee (SRC): 
Safety Review Committee (SRC) will be established comprising investigators, Fosun medical representatives, 
and medical monitor, etc. 
Key roles of the SRC are as follows: 
• 
Before progression to the next age group (elderly group), assess the safety and tolerability data of the 
subjects completed safety visits up to 14 days after prime vaccination, and decide whether to approve 
initiation of the dose cohort of elderly group. Data collected include vital signs, TEAEs, local reactions, 
blood/clinical laboratory data, and brief physical examination outcome. 
• 
Before each dose cohort begins boost vaccination, for each dose cohort, assess the safety and tolerability 
data of the prime vaccination of subjects (including data collected at least up to 14 days post-vaccination) 
and, decide whether to approve initiation of boost vaccination of this dose cohort. Data collected include 
vital signs, TEAEs, local reactions, blood/clinical laboratory data, and brief physical examination outcome. 
• 
Throughout the trial, assess whether to replace trial subjects permanently discontinued due to safety issues. 
• 
Throughout the trial, the SRC may specific additional dose levels to be tested and an appropriate regime for 
enrollment and safety oversight. 
See SRC charter for more information. The SRC will act according to written procedures described in SRC 
charter. 
Independent Data Monitoring Committee:  
The study will be overseen by an Independent Data Monitoring Committee (IDMC). IDMC will consist of 3 or 
5 independent members (including epidemiologist, clinical experts, and statistical expert) and 1 independent non-
voting statistician. 
The IDMC is required to review the unblinded data when a significant event or risk that could cause the study to 
be suspended occurs. Based on the results of the safety data review, IDMC can request the suspension of 
investigation in a certain dose group/age group, or suspension of boost vaccination, and can also provide 
recommendations for subsequent development based on the periodical study data. This study will proceed in 
accordance with the protocol-specified procedures if no IDMC recommendation for suspension or modification 
is received.  
The IDMC meetings will consist of open and closed face-to-face meetings or teleconference calls. The type and 
frequency of scheduled meetings will depend on the subject enrollment and safety event rates. Unscheduled ad 
hoc meetings will occur if a stopping rule occurs, or at any time consultation is requested by the 
Pharmacovigilance Study Team.   
The IDMC will review safety data on an ongoing basis, when the reported AEs meet with the dose-limiting 
toxicity (DLT) criteria, the IDMC will review all relevant safety data and consider a possible pause of the study, 
if it deems necessary:  
See IDMC charter for more information. The IDMC will act according to written procedures described in IDMC 
charter.  
BNT162-03 Version 3.0 (5 AUG 2020)  

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
                                                                                                                                                                                              Page 25 of 116  
Protocol Amd 3, Version 3.0                                                                                                                                                                                      
 5 AUG 2020 
  
Confidential  
should be documented in the subject’s source document and transcribed into the electronic Case Report Form (eCRF). For any procedures at the site, the investigator shall 
follow his/her standard practice. 
d  
Vital signs will be performed at each on site visit, and at 1, 3, and 6 h (±15 min) post each immunization. Vital signs include systolic/diastolic blood pressure, pulse rate, 
respiratory rate, and body temperature. 
e  
In WOCBP women only: collect blood sample for testing β-hCG. 
f  
Urine analysis: glucose, bilirubin, ketone, specific gravity, blood, pH, protein, urobilinogen, nitrite, and leukocytes. Microscopic urinalysis (based on dipstick results): urine 
sediment will be microscopically examined for the presence of red blood cells, white blood cells, casts, crystals, epithelial cells, and bacteria. 
g  
Clinical laboratory: (Chemistry) alkaline phosphatase, creatinine, ferritin, C-reactive protein, albumin, alanine aminotransferase, amylase, aspartate aminotransferase, gamma 
glutamyl transpeptidase, total bilirubin, blood urea, fasting blood sugar, lipase, sodium, potassium, calcium; (Hematology) hemoglobin, hematocrit, red blood cell count, white 
blood cell count and differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count. 
h  
Clinical laboratory tests (thyroid function): triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone. 
i  
Clinical laboratory tests (coagulation function): prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT)), fibrinogen (FIB).  
j  
SARS-CoV-2 testing, including RT-PCR test of nasopharyngeal swabs and SARS-CoV-2 antibodies screening. See Appendix C for procedures of collecting and handling 
specimens of nasopharyngeal swabs. 
k  
Eligible virus naïve subjects with normal chest CT image enrolled at Screening will enter each cohortwill be randomized to vaccination of BNT162b1 or placebo at Visit 1, 
within 7 days after Screening Visit 0. 
l  
Each randomized subject will receive two doses of either BNT162b1 (10 or 30 µg) or placebo intramuscularly (IM) – one vaccination each at Visit 1 (on Day 1) and at Visit 5 
(on Day 22), conduct injections at one third of the deltoid muscle (preferably in the non-dominant arm). 
m  
 
 
n  
Each subject will receive diary cards to collect solicited reactions for 14 days after each vaccination (including the days of vaccine/placebo vaccination), and unsolicited AEs 
for 21 days after prime vaccination and 28 days after boost (including the days of vaccine/placebo vaccination). 
o  
From the beginning of prime vaccination to 28 days after boost, local reaction assessment should be conducted at 1, 3 and 6 h (±15 min) after each vaccination and at each site 
visit after vaccination.  

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
                                                                                                                                                                                              Page 30 of 116  
Protocol Amd 3, Version 3.0                                                                                                                                                                                      
 5 AUG 2020 
  
Confidential  
l  
Each randomized subject will receive two doses of either BNT162b1 (10 or 30 µg) or placebo intramuscularly (IM) – one vaccination each at Visit 1 (on Day 1) and at Visit 5 
(on Day 22), conduct injections at one third of the deltoid muscle (preferably in the non-dominant arm). 
m  
 
 
n  
Each subject will receive diary cards to collect solicited reactions for 14 days after each vaccination (including the days of vaccine/placebo vaccination), and unsolicited AEs 
for 21 days after prime vaccination and 28 days after boost vaccination (including the days of vaccine/placebo vaccination). 
o  
From the beginning of prime vaccination to 28 days after boost vaccination, local reaction assessment should be conducted at 1, 3 and 6 h (±15 min) after each vaccination and 
at each site visit after vaccination. 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 32 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
3.0 
LIST OF ABBREVIATIONS 
AE  
AESI 
Adverse Events  
Adverse Event of Special Interest 
BMI  
Body Mass Index  
BNT162b1 
BNT162 RNA-LNP vaccine utilizing nucleoside modified messenger RNA 
(the variants BNT162b1 will be tested in this trial) 
CI  
Confidence Interval  
CMI 
Cell-mediated Immunity 
CRO  
Contract Research Organization  
CoV 
Corona Virus 
COVID-19 
Coronavirus Disease 2019 
CT 
Computed Tomography 
DLT 
Dose Limit Toxicity (ies) 
DMC  
Data Monitoring Committee  
eCRF  
electronic Case Report Form   
EDC  
Electronic Data Capture system  
ELISA  
Enzyme-linked Immunosorbent Assay  
 
 
EMA 
European Medicines Agency 
GBS  
Guillain-Barré Syndrome  
GCP  
Good Clinical Practice  
GLP 
Good Laboratory Practice 
GMT  
Geometric Mean Titres  
β-hCG  
Beta Human Chorionic Gonadotropin  
HIV  
Human Immunodeficiency Virus  
IB  
Investigator Brochure  
ICF  
Informed Consent Form   
ICH  
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use  
ICS 
Intracellular Cytokine Staining 
IDMC 
Independent Data Monitoring Committee 
IEC  
Independent Ethics Committee  
Ig  
Immunoglobulin  
IM  
Intramuscular Injection 
IMP 
Investigational Medicinal Product; in this trial, BNT162b1 vaccines 
IRB  
Institutional Review Board  
ISF 
Investigator’s Site File 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 33 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
LOD  
Limit of Detection 
mRNA 
Messenger RNA 
MedDRA  
Medical Dictionary for Regulatory Activities  
modRNA 
Nucleoside Modified Messenger RNA 
NHP  
Non-Human Primate  
NMPA 
National Medical Products Administration 
PBS  
Phosphate Buffered Saline solution, ie, water-based salt solution containing 
potassium dihydrogen phosphate (KH2PO4), sodium hydrogen phosphate 
(Na2HPO4), and sodium chloride  
PEI 
Paul-Ehrlich-Institute 
PPS  
Per-Protocol Analysis Set  
PT  
Preferred Term  
RBD 
Receptor Binding Domain 
RNA-LNP 
RNA Lipid Nanoparticle 
RT-PCR  
Reverse Transcription-Polymerase Chain Reaction  
SAEs  
Serious Adverse Events  
saRNA 
Self-amplifying Messenger RNA 
SAP  
Statistical Analysis Plan  
SARS 
Severe Acute Respiratory Syndrome 
SARS-CoV-2 
The virus leading to COVID-19 
SCR  
Seroconversion Rate  
SOC  
System Organ Class  
SPR  
Seropositivity Rate  
SRC 
Safety Review Committee (SRC) 
SUSAR  
Suspected Unexpected Serious Adverse Reaction  
TEAE 
Treatment Emergent Adverse Event 
TMF 
Trial Master File 
TVC 
Total Vaccinated Cohort 
uRNA 
Non-modified Uridine Containing Messenger RNA 
VED 
Vaccine Enhances Disease 
WHO  
World Health Organization  
WOCBP 
Women Of Child Bearing Potential 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 34 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
4.0 
INTRODUCTION  
4.1 Background  
4.1.1 SARS-CoV-2  
SARS-CoV-2 is a single-stranded positive-sense ribonucleic acid (RNA) virus which belongs to 
the coronavirus family that presents about 78% of structural similarities with other members of the 
coronavirus, including SARS virus. Coronaviruses are a large family of viruses that are common 
in many different species of animals, including camels, cattle, cats, and bats. It is rarely for animal 
coronaviruses to infect people and then spread among infected people just like SARS-CoV-2. [1] 
The genetic sequence of the SARS-CoV-2 became available to the WHO and public (MN908947.3) 
On January 12th, 2020, and the virus was categorized into the Beta-coronavirus subfamily. By 
sequence analysis, the phylogenetic tree revealed a closer relationship to severe acute respiratory 
syndrome (SARS) virus isolates than to another Coronavirus infecting humans, namely the Middle 
East respiratory syndrome (MERS) virus. 
Coronaviruses are a (+) ssRNA enveloped virus family that encode for a total of four structural 
proteins. Within these four structural proteins, the spike protein (S protein) is the most dominant 
one when it comes to vaccine development. Like the influenza virus hemagglutinin, the S protein 
itself is responsible for receptor-recognition, attachment to the cell, infection via the endosomal 
pathway, and the genomic release driven by fusion of viral and endosomal membranes. Caused by 
the multiple functions of the S protein, the immune system targets this antigen with antibodies, 
which were shown to have the capacity of virus neutralization. [6] 
4.1.2 Epidemiology  
SARS-CoV-2 was discovered in January 2020 in Wuhan. The first human disease cases were 
reported in December 2019 in China. The virus circulated in areas of over 200 countries 
worldwide, and was considered Acute Respiratory disease syndrome (COVID-19) with mild to 
severe symptoms. The primary mode of transmission of SARS-CoV-2 is person-to-person contact 
through respiratory droplets. Patients with mild or asymptomatic infections may account for 60% 
of all infected patients. Some clinical manifestations include, but are not limited to, fever, cough 
and diarrhea. [2, 3] 
Despite mild clinical symptoms in most adults, SARS-CoV-2 infection over 65 years old has been 
associated with serious outcomes. The severity of the disease is related to the attacks of 
autoimmunity on pulmonary alveoli. Since the beginning of these outbreaks and up to mid-May, 
there has been more than 4,580,000 confirmed COVID-19 associated with SARS-CoV-2 infection 
with over 310,000 deaths in over 200 countries, areas or territories worldwide. [4]  
SARS-CoV-2 is a respiratory virus that can cause disease of the respiratory system. The overall 
incidence of SARS-CoV-2-associated COVID-19 is unknown currently. In the epidemic curve up 
to January 4, 2020, the epidemic growth rate was 0.10 per day (95% CI, 0.050 to 0.16) and the 
doubling time was 7.4 days (95% CI, 4.2 to 14). Using the serial interval distribution above, we 
estimated that R0 was 2.2 (95% CI, 1.4 to 3.9) [3].  

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 35 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
No specific antiviral treatment is available for SARS-CoV-2 infections and no vaccine against 
SARS-CoV-2 is currently available. As the disease is self-limiting, treatment for uncomplicated 
SARS-CoV-2 infection is supportive and focuses on symptoms. The main recommendations to 
prevent outbreaks are through social distancing (avoiding person-to-person contact transmission), 
and personal protective equipment (PPE) measures.   
The risk of infection with SARS-CoV-2 is increasing given that the spread of SARS-CoV-2 is rapid 
and intense in over 200 countries, areas, or territories. SARS-CoV-2 has posed a challenging 
situation for health, public and economic sectors of affected countries. 
The World Health Organization (WHO) declared on 30 January 2020 the SARS-CoV-2 outbreak 
as a Public Health Emergency of International Concern (PHEIC) and recommended to focus the 
research on the causal association of SARS-CoV-2 infection. Considering the spread to more new 
countries, this novel coronavirus disease COVID-19 outbreak was assessed as very high of global 
risk level on February 28 2020, and was characterized as a pandemic by the WHO on March 11 
2020.[4] 
4.2 Rationale of trial plan   
4.2.1 Medical need  
Considering the conclusive associations between SARS-CoV-2 infections and severe acute 
respiratory syndrome, the development of a vaccine that can provide protection is crucial for 
countries where the epidemic is expected to arrive and/or persist, as well as in countries in which 
the virus has not yet been epidemic. In order to address the urgent medical need and in anticipation 
of possible outbreaks with rapid onsets, the sponsor has initiated the development of a SARS-CoV-
2 vaccine (BNT162b1), for use in endemic areas and non-endemic areas for prevention of SARS-
CoV-2 associated illness of any severity and/or infection.  
The urgent engagement in the efforts to investigate, make available safe and effective SARS-CoV-
2 interventions are needed to control the outbreak. Given the severity of the situation, time to 
vaccine development was an important aspect of the highly unmet needs. In response to this need, 
an accelerated vaccine development effort was initiated. 
4.2.2 RNA vaccines under development  
A LNP-formulated RNA based vaccine would provide one of the most flexible, scalable and fastest 
approaches to provide protection against the emerging viruses like SARS-CoV-2.[7, 8] 
The development of a RNA-based vaccine encoding a viral antigen that is translated by the 
vaccinated organism to protein to induce a protective immune response provides significant 
advantages over more conventional vaccine approaches. Unlike live attenuated vaccines, RNA 
vaccines do not carry the risks associated with infection and may be given to people who cannot 
be administered live virus (such as pregnant women and immunocompromised persons). RNA-
based vaccines are manufactured via a cell-free in vitro transcription process, which allows an easy 
and rapid production and the prospect of producing high numbers of vaccination doses within a 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 36 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
shorter time period than achieved with conventional vaccine approaches. This capability is pivotal 
to enable the most effective response in outbreak scenarios. 
The development of in vitro transcribed RNA as an active platform for the use in infectious disease 
vaccines is based on the extensive knowledge of this study’s sponsor, BioNTech in RNA 
technology, which has been gained over the last decade. The core innovation is based on in vivo 
delivery of a pharmacologically optimized, antigen-encoding RNA to induce robust neutralizing 
antibodies and a concomitant T cell response to achieve protective immunization with minimal 
vaccine doses.[9-11] 
A recently published clinical trial using an influenza vaccine based on modRNA encapsulated in 
LNPs highly related to those used in this trial and administered IM reported a consistent pattern of 
reactogenicity but overall good safety and tolerability. [12] 
4.2.3 Summary of available non-clinical data  
4.2.3.1  Non-clinical pharmacology studies  
The primary pharmacodynamics of the BNT162 vaccine was investigated in a range of non-
clinical pharmacology studies in vitro and in vivo. Expression of RNA-encoded antigens was 
investigated in vitro. The mode of action of BNT162b1 vaccine was investigated with 
immunogenicity data in mice. The antibody response induced by RNA-encoded antigens was 
investigated by enzyme-linked immunosorbent assay (ELISA) and pseudovirus neutralization 
assay (pVNT). 
To assess the potency of the LNP-formulated modRNA vaccine candidate BNT162b1, which 
encodes RBD V5, BALB/c mice were immunized IM once. ELISA data from sera obtained 7, 14 
and 21 d after immunization show an early, dose-dependent IgG response recognizing S1 and the 
RBD (Figure 2). 
 
 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 39 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Figure 4  Neutralization of SARS CoV-2 pseudovirus 14, 21 and 28 d after immunization 
with BNT162b1 
BALB/c mice were immunized IM once with 0.2, 1 or 5 μg of BNT162b1. On 14, 21 and 28 d 
after immunization, animals were bled, and the sera were tested for SARS CoV-2 pseudovirus 
neutralization. Graphs depict pVN50 serum dilutions (50% reduction of infectious events, 
compared to positive controls without serum). One point on the graphs stands for one mouse. Every 
mouse sample was measured in duplicate. Group size n=8. Mean ± SEM is depicted by a horizontal 
line with whiskers for each group. LLOQ, lower limit of quantification. ULOQ, upper limit of 
quantification. 
4.2.3.2  Non-clinical pharmacokinetic studies   
Pharmacokinetic studies were conducted using a luciferase reporter RNA, and protein expression 
after IM injection was demonstrated in vivo. The luciferase biodistribution profile resembles that 
of similar RNA products developed by BioNTech, some of which have been tested for safety at 
higher doses non-clinically and clinically using IV administration. Prior clinical experience with 
similar RNA products developed by BioNTech indicates that the distribution of vaccines in the 
liver does not pose a safety risk. But the liver parameters still will be carefully monitored during 
the clinical development of the BNT162b1 vaccines. 
4.2.3.3 Toxicologic study   
Through the study on GLP compliance repeat-dose toxicity in Wistar Han rats and, until data cut-
off date, through the recovery phase of the repeat-dose toxicity study, there were no clinical signs 
or mortalities observed. As expected, the BNT162b1 vaccines induce a pro-inflammatory response, 
which manifests in a reduction in body weight (up to approximately 13%) 24 h post immunization 
without affecting body weight gain overall. The temporary weight loss is probably caused by 
shortly reduced food and water consumption after administration, which also leads to less urine 
production immediately after immunization. The observed increases in typical inflammatory blood 
parameters (such as fibrinogen and acute phase proteins) support this hypothesis. The transient and 
reversible elevation of GGT activity in serum in the absence of elevation of liver specific 
inflammation markers, such as ALAT or ASAT is considered a general inflammation marker. 
Few hematological changes were observed: an increase in large unclassified cell and leukocyte 
(monocyte and neutrophil) counts, as well as a transient, dose-dependent reduction in reticulocytes 
after first immunization. The reduction in reticulocytes was reversed under continued 
immunizations and did not affect erythrocyte or hemoglobin levels and is species-specific. These 
changes have been observed in rats treated with the licensed LNP-small interfering RNA (siRNA) 
pharmaceutical Onpattro™ (FDA assessment report of Onpattro™ 2018), but have not been 
observed in patients treated with this compound. After the last immunization, a slight reduction in 
platelet numbers was observed. This effect is most likely attributable to inflammation specific 
platelet consumption and though it mediates a slight prolongation of aPTT in Groups 3, 4, 5, 6 and 
7 of 2-3 seconds, it is not considered a safety concern but rather a pharmacodynamics attribute. 
As an induction of a local pro-inflammatory environment within the muscle, which promotes 
potent immune responses, can be considered a mode of action of BNT162b1 vaccines, local 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 40 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
reactions were anticipated. The only local reactions observed after the first immunization were 
very slight to slight (grade 1 - 2) edema. Of note, no grade 3 or 4 local reactions occurred after the 
first immunization. The occurrence of higher grade of local reactions after boost immunizations is 
considered to be attributable to the undiluted status of the vaccines and to the - in relation to body 
weight of the rat - high vaccine dose (approximately up to 0.5 mg/kg), in addition to the short 
interval of 7 d between immunizations. It is not anticipated to occur in the clinical trial, in which 
boost immunizations of a maximum dose of 0.002 mg/kg (e.g., for the highest dose of 100 μg in a 
participant weighing 50 kg) will be administered 21 d apart. 
Macroscopic observations of indurated injection sites and - in some animals - enlarged spleens 
and/or draining lymph nodes together with a tendency of increased spleen weights in vaccinated 
animals, support the hypothesis that the vaccine candidates generate a pro-inflammatory 
environment. In rats, the potent immune response observed can already be detected 17 d post first 
immunization. 
Taking together the previous non-clinical and clinical experience with the preliminary results of 
the BNT162b1 vaccine toxicity study, a benign clinical safety profile is anticipated. 
4.2.4 Summary of available clinical data  
Two Phase I/II clinical studies of BNT162b1 are currently being conducted in Germany and the 
United States; at the same time, the immunogenicity, repeated dose toxicology study and viral 
challenge study are conducted in BALB/c mice in accordance with Good Laboratory Practice 
(GLP) to continuously analyze the efficacy and safety of BNT162b1 at animal level and human 
body level. Interim Report of the United States Phase I/II clinical study has been published [5]. 
Results of data analyses for pre-clinical studies and clinical studies will be provided by 
continuously updating in the Investigator's Brochure (IB). The clinical studies conducted in 
Germany and the United States are first-in-human trials, so dose escalation mode is adopted and 
sentinel subjects are added for both. The maximum dose examined in these two studies is 100µg, 
and the safety result shows that the local reaction of vaccination site and systemic event are dose-
dependent which is mostly mild to moderate with short duration, reactions after two vaccinations 
are similar, and reaction is slightly less in elderly group; immunogenicity result shows that serum 
RBD specific IgG antibody concentration and SARS-CoV-2 neutralizing antibody titer escalate 
with dose level and increase after booster vaccination. The geometric mean neutralizing titer is 1.8 
to 2.8 times that of a group of COVID-19 human serum during recovery period. Above results will 
support the further evaluation of the mRNA candidate vaccine. Currently, the optimal dose range 
is predicted as 10~30 µg according to safety and efficacy data of foreign subjects. Since the 
preliminary safety and immunology data are obtained, and clinical studies conducted in Germany 
and the United States will continue to support studies in China, so China plans to conduct bridging 
trial to confirm foreign study results among Chinese subjects. 
 
4.2.4.1 Safety summary 
According to the periodic summary of the United States Phase I/Ⅱ clinical study, pain at the 
injection site was the most common local reaction within 7 days of the first dose and the second 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 41 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
dose of vaccine; after the first vaccination, probability of pain in 10 µg group was 58.3% (7/12), 
in 30 µg group and 100 µg group were 100.0% (12/12), and in placebo group was 22.2% (2/9). 
After the second vaccination, there were 83.3% and 100.0% of subjects got pain respectively in 
the dose level of 10 µg and 30 µg, while 16.7% subjects in placebo group got pain. All local 
reactions were mild or moderate except the 100 µg group reported severe pain after inoculation of 
BNT162b1.  
Within 7 days of each vaccination, the most common systemic events reported in BNT162b1 and 
placebo groups were mild to moderate fatigue and headache. Fatigue and headache were more 
common in BNT162b1 than that in placebo group. Furthermore, chills, muscle pain and joint pain 
were reported in the BNT162b1 group, but not in the placebo group. Systemic events increased 
with dose levels, and there were an increased number of subjects reporting systemic events after 
the second vaccination (10 µg and 30 µg groups). After the first vaccination, there were 8.3% (1/12) 
of subjects respectively in 10 µg group and 30 µg group, and 50.0% (6/12) of subjects in 100 µg 
group got fever (defined as ≥38.0°C). Based on the reactogenicity reported after the first dose 
of 100 µg and the second dose of 30 µg, subjects initially received 100 µg of vaccination will no 
longer receive the second vaccination. After the second vaccination, 8.3% (1/12) of subjects in 10 
µg group and 75.0% (9/12) of subjects in 30 µg group got fever ≥38.0°C. The fever usually got 
resolved within 1 day of onset. There was no systemic event or fever of grade 4. Most local 
reactions and systemic events peaked 2 days after vaccination and resolved at day 7.  
Subjects received 10 µg or 30 µg BNT162b1 reported 50.0% (6/12) of adverse events, subjects 
received 100 µg BNT162b1 reported 58.3% (7/12), and placebo group reported 11.1% (1/9). 2 
subjects reported severe adverse events: fever of grade 3 was reported 2 days after vaccination in 
the 30 µg group, and sleep disturbances was reported 1 day after vaccination in the 100 µg group. 
Rate of related adverse events reported in BNT162b1 group was 25% (10 µg group was 3/12) tp 
50% (30 µg and 100 µg groups each was 6/12), placebo group was 11.1% (1/9). No serious adverse 
event.  
After BNT162b1 vaccination, most subjects had no change in routine clinical laboratory values or 
laboratory abnormalities of level 1 or above. Among patients with changes in laboratory values, 
the biggest change was a decrease in lymphocyte count after the first dose of vaccine, 10 µg, 30 
µg and 100 µg were respectively 8.3% (1/12), 45.5% (5/11) and 50.0% (6/12). There was 1 each 
in the dose level of 10 µg group (8.3% [1/12]) and 30 µg group (9.1% [1/11]), and 4 in 100 µg 
group (33.3% [4/12]) that reported lymphopenia of grade 3. The decrease in lymphocyte count 
after the first vaccination was transient and it returned to normal 6-8 days after vaccination. In 
addition, 1 subject each in the 10 µg group or 30 µg group was reported to have neutropenia of 
grade 2 6-8 days after BNT162b1 boost injection. Both subjects were followed up in the study, and 
no adverse events or clinical manifestations of neutropenia have been reported to date. All of the 
observed post-vaccination abnormalities were unrelated to clinical findings. 
 
4.2.4.2 Immunogenicity summaries 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 42 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
According to the periodic summary of the United States Phase I/Ⅱ clinical study, geometric mean 
concentration (GMC) of RBD specific IgG was 534-1,778 U/mL 21 days after prime vaccination. 
In contrast, RBD specific IgG GMC was 602 U/mL in 38 samples of sarS-COV-2 infection 
/COVID-19 convalescent human serum taken from patients aged 18-83 years old and at least 14 
days after PCR confirmation. 7 days after the second vaccination (at dose levels of 10 µg and 30 
µg), the GMC of RBD specific IgG antibody increased to 4,813-27,872 U/mL. 21 days after prime 
vaccination, RBD specific antibody concentrations were not increased in subjects who received 
the first dose of 100 µg BNT162b1. In subjects receiving doses of 10 µg and 30 µg BNT162b1, 
high concentrations of RBD specific antibodies persisted until the last time point so far assessed 
(day 35 of the trial, 14 days after the second vaccination). These RBD-binding antibodies were 
present at concentrations of 5,880-16,166 U/mL.  
For all dose groups, a moderate increase in SARS-COV-2 neutralizing geometric mean titer (GMT) 
was observed 21 days after the first vaccination. 7 days after the second dose of 10 µg or 30 µg 
vaccine, the GMT of serum neutralizing antibody was significantly increased to 168-267, while 
the GMT of human serum during recovery was 94. 
4.2.5 BioNTech RNA-based vaccine candidate  
BioNTech has three different RNA platforms under development, namely non- modified uridine 
containing mRNA (uRNA, BNT162a), nucleoside modified mRNA (modRNA, BNT162b), and 
self-amplifying mRNA (saRNA, BNT162c). 
All three RNA platforms have been tested in more than a dozen non-clinical GLP safety studies 
and, for uRNA and modRNA, there is pre-existing clinical safety data (see the BNT162 
investigator’s brochure [IB]). These data have been obtained primarily with RNAs formulated with 
liposomes which are related, but not identical, to those to be used in this trial. 
The non-clinical toxicity data generated by BioNTech suggest a favorable safety profile for uRNA, 
modRNA, and saRNA formulated with different nanoparticles for various administration routes 
including for intravenous (IV) injection. The favorable safety profile after IV dosing is notable 
because it results in a higher systemic exposure than the planned IM dosing in this trial. Overall, 
the findings were mild adverse events and mostly related to the mode-of-action and the RNA-
intrinsic stimulation of innate immune sensors. No unsuspected target organs of toxicity were 
identified. The non-clinical safety profile of uRNA and modRNA in rodents was predictive for 
clinical safety. For further details, see the BNT162 IB. 
Phase I/II clinical study of BNT162b1 is currently conducted in Germany and the United States, 
and the effect and safety of BNT162b1 has been persistently observedat the animal level and 
human body level in a Good Laboratory Practice (GLP)-compliant, immunogenicity, repeat-dose 
toxicological study and virus challenge study in BALB/c mice. Data analysis results will be 
provided in the Investigator Brochure (IB) in a form of continuous updates. An optimal dose range 
of 10~30 µg has been identified in foreign subjects, based on safety and efficacy data.  

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 43 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
4.2.6 Rationale for BNT162-03 trial  
BNT162-03 is a phase I, dose confirmation study, which adopts a parallel two-dose cohort and 
placebo design in adult healthy subjects (adult group) and elderly healthy subjects (elderly group); 
and the trial in adult group is conducted firstly and followed by the trial in the elderly group. And 
the study is intended to confirm that the response (safety/immunogenicity) seen in foreign subjects 
is comparable to that observed in Chinese subjects. Healthy adults who are ≥18 years old and ≤55 
years old will be enrolled in adult group, and healthy elderly subjects who are ≥65 years old and 
≤85 years old will be enrolled in elderly group. To ensure the enrollment of healthy subjects, 
screening tests (hematology, biochemistry, and urinalysis) will be performed prior to 
vaccine/placebo vaccination. In each age group of subjects, the testing is conducted according to 
the parallel two-dose cohort and placebo allocation. The design of this study, including the 
selection of two optimal dose levels are informed by safety and immunogenicity data from the 
ongoing or completed foreign studies of BNT162b1.In this study, a Safety Review Committee 
(SRC) will be comprised of investigators, Fosun medical representative and medical monitor, and 
SRC will review the safety data in a blinded way. SRC will review the available safety and 
tolerability data of all subjects in this cohort (including at least safety laboratory test results and 
safety events collected in diary cards within 14 days after the prime vaccination) before starting 
the boost vaccination for each cohort to suggest whether the boost vaccination of BNT162b1 
vaccine can be conducted. Data from the ongoing foreign clinical studies may be used to help 
select optimal doses for testing in this study. The study will also set up an Independent Data 
Monitoring Committee (IDMC) to conduct overall supervision. The IDMC is required to review 
the unblinded data when a significant event or risk occurs in the study that could cause the study 
to be suspended. 
Due to the ongoing threat of SARS-CoV-2 disease and the urgent need of a vaccine, this study will 
be accelerated to assess the bridging data for BNT162b1, in addition to confirm that the response 
(safety/immunogenicity) seen in foreign subjects is comparable to that observed in Chinese 
subjects. 
Placebo serves as the control for the study vaccine and in the absence of effective treatment or 
prevention for COVID-19, the use of placebo in this trial is justified. Based on the different 
physical appearance of the investigational vaccine compared to the saline solution placebo that 
will be selected, an independent non-blind team is adopted in this study for blinding subjects and 
observers.  
All enrolled subjects will receive two doses of either SARS-CoV-2 vaccine (BNT162b1) or 
placebo intramuscularly (IM) on Day 1 and on Day 22. The objective of the study BNT162-03 is 
to assess the safety and immunogenicity of BNT162b1 in the Chinese healthy subjects.   
The primary rationale for selection of the two-vaccine dose levels can be summarized as follows:   
Based on the clinical data from the overseas clinical studies, and the non-clinical data of the RNA 
components (modRNA), with other liposomes or in conjunction with the lipid nanoparticles as will 
be tested clinically in this trial, we expects that doses at the 1~5 μg range will be immunogenic 
and induce neutralizing antibodies. The dose range of 1~100 µg has been identified in foreign 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 44 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
subjects, based on safety and efficacy data. Accordingly, a degree of reactogenicity is anticipated 
with BNT162b1 with mild or moderate local or systemic reactions common amongst subjects. 
Based on currently available data on safety and immunogenicity of global clinical trials in 
Germany and the United States, two predicted optimal doses are selected to confirm the 
comparability of safety and efficacy for BNT162b1 in China. 
• 
the low-dose level (10 µg);  
• 
the high-dose level (30 µg). 
The trial will be conducted in accordance with the protocol, the International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) GCP 
Guidelines and applicable regulatory requirements.  
4.3 Benefit/risk assessment   
4.3.1 Risk assessment  
The risks linked to the trial-specific procedures and connected mitigations are as follows: 
• Throughout the trial period (i.e. approximately 12 months), the volume of blood drawn per 
subject will be kept to a minimum and will remain less than that drawn when donating blood. 
• All trial-specific procedures will be performed by qualified study site personnel. 
• Vaccination will be done by a physician or designee under medical supervision. 
• Two Phase I/II clinical study studies of BNT162b1 are currently being conducted in Germany 
and the United States. There are no published clinical data currently available for BNT162b1. 
However, clinical data is available for RNAs formulated with related but not identical liposomal 
compositions or non-formulated RNAs and can support risk assessment of BNT162 products. 
Based on such data, the risks linked to the immunization with the BNT162b1 vaccines are as 
follows: 
• Due to the IM route of administration, there is the risk of local reactions at the vaccination site, 
e.g., flush, pruritus, pain, tenderness, swelling, sweating. 
• Due to the immune-modulatory effect, vaccines may cause systemic flu-like reactions such as 
temporary headache, fatigue, loss of appetite, myalgia, arthralgia, fever. Rarely, with certain 
prophylactic vaccines (e.g., as seen for vaccines using attenuated viruses) severe allergic 
reaction or a neurological side effects, such as a seizure, were seen. Although these rare side 
effects are a concern, the risk of a vaccine causing serious harm or death is extremely small, for 
BNT162b1 vaccines, which are molecularly defined, highly purified, and based on RNA, which 
naturally occurs and is metabolized in the human organism. 
• Due to the IM route the risk of systemic reactions is considered low. 
An IM vaccine based on modRNA encapsulated into a related but not identical vaccination has 
reported mostly mild to moderate, mostly local solicited AEs (mostly vaccination site pain) of 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 45 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
1~3 days duration that resolved without intervention. Fever was the only systemic solicited AE. 
[12] 
• As with other vaccines and with single stranded RNA being an innate immune sensor-agonist, 
BNT162b1 administration may cause temporary headache, fatigue, or loss of appetite. Rarely, 
with certain prophylactic vaccines (e.g., as seen for vaccines using attenuated viruses) severe 
allergic reaction or a neurological side effects, such as a seizure, were seen. Although these rare 
side effects are a concern, the risk of a vaccine causing serious harm or death is extremely small, 
for BNT162b1 vaccines, which are molecularly defined, highly purified, subunit vaccines. 
• The available non-clinical data of BNT162b1 suggest a favorable safety profile with events that 
are mild and mostly related to the mode-of- action and the RNA-intrinsic stimulation of innate 
immune sensors. 
Based on the available clinical and non-clinical data on the RNA component (uRNA) and 
individual components of the related RNA platform (modRNA, saRNA), that are combined 
within the BNT162 products, a favorable safety profile of BNT162b1 products is expected with 
mild and localized effects (see the IB for details on these trials). 
o IV administration to cancer patients of uRNA in a different liposomal formulation (i.e., 
uRNA-LPX) had a favorable safety profile. In these trials’ systemic exposure at doses up to 
400 μg to uRNA-LPX IV was tolerated without dose limiting toxicities. In line with the 
transient secretion of a distinct range of cytokines observed in these patients, the AE profile 
was found to be dominated by mild to moderate flu-like symptoms, e.g., pyrexia and chills. 
These immune modulation-related AEs started within 2-6 h after IV injection, resolved 
within 24 h. 
o Non-formulated uRNA administered in oncological trials intradermally or injected into 
inguinal lymph nodes was tolerated with only occasional and mild local reactions. Systemic 
reactions after local application were not observed. 
o Non-formulated modRNA administered in buffer into tumor lesions of cancer patients was 
tolerated with occasional mild local reactions. Systemic reactions after local application 
were not observed. 
• To date, there is very limited clinical experience with BNT162b1 vaccines in human subjects. 
Reactogenicity is anticipated and considered to contribute to the mode-of-action of inducing 
vaccine immune responses. Initial dose-ranging studies have suggested AE profiles consistent 
with previous usage of similar constructs in cancer patients, with AEs generally dividing into 2 
groups: local injection site reactions and systemic flu-like illness. With BNT162b1 vaccines to 
date most reported AEs have been mild to moderate in intensity and no serious AEs have been 
reported. Fever of severe intensity has been reported. Most AEs can be managed with simple 
measures and resolve spontaneously. Short-lived effects can be seen on immune parameter due 
to the PD effects, such as lowering of lymphocytes due to temporary trafficking in to the lymph 
system, or raising of CRP. These are only regarded as AEs if there are clinical consequences. 
The listed risks can be managed using routine symptom driven standard of care as described in 
Section 10.5. Treatment of these events is dependent on the discretion of the investigators. 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 46 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
The trial uses placebo control parallel design, to ensure trial subject safety during the trial. To 
further ensure trial subject safety, the trial protocol foresees that: 
 • They are much longer than used in recently completed FIH clinical trials investigating related 
RNA-based vaccines. For example, the two Moderna trials investigating mRNA vaccines 
against avian H10N8 and H7N9 influenza viruses in healthy adults that observed trial subjects 
on-site for only 1 h after each immunization before discharge from the trial site.[12] 
• More frequent on-site visits after immunization (i.e., on Days 2 and 8) than used in recently 
completed FIH clinical trials investigating with related RNA-based vaccines, e.g., the two 
Moderna trials investigating mRNA vaccines against avian H10N8 and H7N9 influenza viruses 
in healthy adults that used on-site visits on Day 8.[12]  
• Additional subject wellbeing calls may be included at the discretion of the SRC.  
• In the case that an individual experiences dose limiting toxic events or that the frequency or 
pattern of AEs within a sub-cohort gives cause for concern, the investigator may request an ad 
hoc review by the SRC before further doses of a given vaccine construct are administered.  
•  
• The SRC must assess the safety and tolerability data of the subjects before allowing progression 
to the next cohort. A 14-day interval was set between the dose cohorts. 
• After each assessment, the SRC may request a prolongation of the observation periods. 
Additional telephone health inquiries may be added. 
SRC may make recommendations on increasing observation periods and additional subject 
wellbeing calls may be included at the discretion of the SRC.  
To ensure trial subject safety during the trial, their safety will be monitored from Visit 0 (screening) 
until approximately 12 months after the last immunization.  
Vaccine-related enhanced disease has been reported in the literature from non-clinical studies 
investigating different vaccine formulations tested to prevent various coronavirus-induced diseases. 
Such effects have not been documented so far for SARS-CoV-2. No data are currently available to 
exclude that BNT162 may cause enhanced disease in vaccinated subjects.  
The risks linked to the pandemic COVID-19 outbreak will be managed by requiring that the trials 
subjects:  
• Avoid contact with persons tested positive for SARS-CoV-2 antibodies or have an increased 
risk for infection during their participation in the trial.  
• Practice social distancing and follow good practices to reduce their chances of being infected 
or spreading COVID-19 during their participation in the trial.  
• Complete health status checks which include symptom directed physical examinations, vital 
signs assessments, and clinical laboratory tests at the planned visit days.  
• Contact the trial site during their participation in the trial should they require guidance or should 
they experience any symptoms of illness. The reporting of any symptoms of illness, e.g., 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 47 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
enhanced respiratory disease or flu-like symptoms, may trigger diagnostic measures at the 
discretion of the investigator.  
To minimize the risk to trial subjects in this trial, SRC and IDMC will regularly review and 
evaluate the safety and immunogenicity data. For details, see Section 11.0.  
4.3.2 Benefit assessment  
After participating in this trial, depending on the immunization regimen followed, some trial 
subjects should be immune against SARS-CoV-2 infection. 
There is an urgent need for the development of new prophylactic vaccines given the threat posed 
by the increasing number of globally distributed outbreaks of SARS-CoV-2 infection. The 
BioNTech platform of RNA-based vaccines being tested in this trial is especially attractive because 
it can deliver high numbers of vaccine doses rapidly in a single production campaign. This platform 
has the added advantage of not employing live virus and could therefore potentially be used for 
immuno-compromised populations. 
By participating in this trial, the trial subjects will help to market these prophylactic vaccines 
against SARS-CoV-2 infection. 
4.3.3 Overall benefit/risk conclusion  
Overall, the Fosun considers the benefit/risk ratio to be acceptable. 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 48 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
5.0  
TRIAL OBJECTIVES AND ENDPOINTS  
5.1 Objectives  
5.1.1 Primary objective  
• 
To assess the safety and tolerability profiles of BNT162b1 prime/boost (P/B) immunization 
given 21 days apart from different dosages in SARS-CoV-2 naïve Chinese healthy subjects 
through 28 days after boost vaccination. 
5.1.2 Secondary objectives  
• 
To observe the immunogenicity of two doses of BNT162b1 (anti-S1 and anti-RBD IgG 
antibodies) given 21 days apart measured by enzyme-linked immunosorbent assay (ELISA). 
• 
To observe the immune response of healthy subjects after BNT162b1 P/B immunization by 
true virus-based SARS-CoV-2 neutralizing antibody detection. 
• 
To observe the safety of BNT162b1 vaccination in Chinese healthy subjects until the end of 
the study.  
• 
To conduct 12-month follow-up for healthy subjects in the BNT162b1 vaccination dose cohorts, 
and observe the sustainability of the immune response to BNT162b1. 
5.1.3 Exploratory objective  
• 
 
 
 
   
 
 
 
 
 
5.2 Endpoints  
5.2.1 Primary endpoints  
Safety and tolerability of BNT162b1, as determined by:  
• 
Occurrence of solicited local reactions in the subjects (eg, vaccination sites: pain/tenderness, 
erythema/redness, induration/swelling) during the 14-day after each dose of BNT162b1 or 
placebo.   
• 
Occurrence of solicited systematic reactions (eg, nausea, vomiting, diarrhea, headache, fatigue, 
myalgia, arthralgia, chills, loss of appetite, malaise, and fever) during 14-day after each dose 
of BNT162b1 or placebo.   

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 49 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
• 
Occurrence of AE associated with vaccination in subjects during the 21-day period after prime 
vaccination and the 28-day period after boost dose of BNT162b1 or placebo.  
5.2.2 Secondary endpoints  
Safety and tolerability of BNT162b1, as determined by:  
• 
The proportion of subjects experiencing SAEs, occuring up to Day 21 after prime vaccination 
and Day 28 after boost vaccination, up to Month 3, 6 and 12.  
• 
The proportion of subjects experiencing AE associated with BNT162b1, occuring up to Month 
3, 6 and 12. 
• 
The proportion of of subjects experiencing abnormal markers of hematology, blood chemistry 
and urine analysis, occuring at Hour 24 and Day 7 after prime vaccination and Day 7 period 
after boost dose of BNT162b1 or placebo.  
Immunogenicity of BNT162b1, as determined by: 
• 
Geometric mean titer (GMT) of anti-S1 IgG antibody at Day 7, Day 21 after prime vaccination, 
at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.   
• 
Geometric mean titer (GMT) of anti-RBD IgG antibody at Day 7, Day 21 after prime 
vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.   
• 
GMT of SARS-CoV-2 neutralizing antibody (including true virus-based SARS-CoV-2 
neutralizing test) at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost 
vaccination, and at Month 3, 6 and 12.  
• 
Fold increase in antibody anti-S1 IgG antibody titers, as compared to baseline, at Day 7, Day 
21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12. 
• 
Fold increase in antibody anti-RBD IgG antibody titers, as compared to baseline, at Day 7, 
Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 
and 12. 
• 
Fold increase in SARS-CoV-2 neutralizing antibody titers (virus neutralizing test), as 
compared to baseline, at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost 
vaccination, and at Month 3, 6 and 12. 
• 
Seroconversion rates (SCR) defined as a minimum of 4-fold increase of antibody titers, as 
compared to baseline, at Day 7, Day 21 after prime vaccination, and at Day 7, Day 21 after 
boost vaccination.  
5.2.3 Exploratory endpoints 
• 
 
 
 
 
 
. 

SARS-CoV-2 mRNA Vaccine   
  
Trial No. BNT162-03 
Page 50 of 116  
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
• 
 
 
6.0 TRIAL DESIGN AND DESCRIPTION  
6.1 Overall trial design  
This is a phase I, randomized, placebo-controlled, observer-blind, safety and immunogenicity 
study of SARS-CoV-2 mRNA vaccine (BNT162b1) in Chinese healthy subjects. 
After randomization, the trial for each subject will last for approximately 12 months. Screening 
period is 2 weeks prior to randomization (Day -14 to Day 0), and two doses of either SARS-CoV-
2 vaccine (BNT162b1) or placebo will be given intramuscularly (IM) on Day 1 and on Day 22. 
After each age group completes the follow-up 28 days after boost vaccination (Day 50), initial 
analysis will be conducted. 
Subjects who are ≥18 years old and ≤55 years old will be enrolled in adult group, and healthy 
elderly subjects who are ≥65 years old and ≤85 years old will be enrolled in elderly group. 
Approximately 72 subjects from each age group are allocated to two-dose cohorts (10 μg and 30 
μg) in parallel, with approximately 24 subjects at each BNT162b1 dose level, 24 subjects in 
placebo goup. The subjects will be randomized in a 1:1:1 ratio to inject BNT162b1 or placebo, 
respectively. 
After the 14-day safety observation post the completion of prime vaccination of the subject in the 
adult group, the prime vaccination for subjects in the elderly group will start. SRC will review the 
available safety and tolerability data of all subjects in a cohort before starting the boost vaccination 
for each cohort to suggest whether the boost vaccination of BNT162b1 vaccine can be conducted. 
A summary of the dose cohort design can be seen in Figure 5 General protocol design (adult 
subjects and elderly subjects), and Figure 1 Schematic diagram of dose allocation design. For the 
planned assessments and visits, see Schedule of activities in Table 2 (adult subjects, elderly 
subjects). 

SARS-CoV-2 mRNA Vaccine   
                                               
Trial No. BNT162-03 
Page 51 of 116   
Protocol Amd 3, Version 3.0  
     5 AUG 2020 
  
Confidential  
 
 
Figure 5 Overall study design: adult subjects (below) and elderly subjects (above) 
 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 52 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
 
 
Figure 1 Schematic diagram of dose parallel design

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 53 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
6.2 Subjects enrollment and dose cohorts  
The study will follow a parallel two-dose cohort and placebo design.  
In the adult group, the enrollment process for subjects is as follows:  
• 
In each planned low-dose cohort, high-dose cohort and placebo group, 72 subjects will be 
randomized in a 1:1:1 ratio to inject BNT162b1 or placebo vaccinated on Day 1.   
• 
If the SRC considers that the subjects are safe with good tolerance after 14 days of 
observation, the boost vaccination will be conducted on Day 22.   
• 
When the subjects in the adult group completed safety visits up to 14 days post prime 
vaccination, the available safety data for all subjects were summarized. If approved by the 
SRC,   
o the planned dose cohort of elderly group will be initiated (see Figure 1).   
The data assessed by the SRC comprises: vital signs, TEAEs, local reactions, 
blood/clinical laboratory data and brief physical examination outcome.   
o The parallel dose cohort study is conducted in the elderly group with consistent 
methods as those in the adult group (see Figure 1).  
6.3 Dose modification 
Any change in planned doses or testing of additional doses must be approved by the SRC. 
6.4 Justification for trial design, dose, and endpoints  
The trial design and the collection of solicited reactions and unsolicited AEs following vaccination 
follows related guidelines on vaccine evaluation trials.  
The design of the study answers to the principles outlined in the ICH Considerations on Clinical 
Trials E8 and the WHO Guidelines for Evaluation of Vaccines, and more specifically for phase I/II 
trials. As such, the study design, objectives, and endpoints were defined to assess the safety and 
reactogenicity of the vaccine candidate, obtain information on its immunogenicity, and provide 
data useful for the design of further clinical studies. The dose-ranging design adopted is in line 
with the ICH guidance. The use of placebo as control for the investigational vaccine is justified in 
the absence of a proven intervention, ie, as no prophylactic vaccine against SARS-CoV-2 infection 
is available to date.   
See Section 4.2.6 for the rationale of trial protocol.  
Please also refer to the IB.  
6.5 Duration of subject’s expected participation in the entire trial  
Each enrolled subject’s participation in the trial will last approximately 12 months after 
randomization, following a two-week screening period prior to randomization (Visit 1). 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 54 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
6.6 Dose limiting toxicity (DLT) 
During the time of enrollment into a given cohort, if any of the following events occur and are 
assessed to be vaccine related, further vaccination in that cohort will be suspended: 
• 
Anaphylaxis reaction considered related; 
• 
Generalized urticaria considered related; 
• 
1/3 trial subjects in that cohort with any severe unsolicited local reaction, if considered related 
and not manageable with simple measures (e.g. cooling, analgesia, nonsteroidal anti-
inflammatory drugs [NSAID]; 
• 
Any possibly related AEs within 7 days of vaccination assessed to be potentially life-
threatening (Grade 4);  
• 
Any systemic SAE within 7 days of vaccination considered related;  
• 
Any fever >40.0°C (>104.0°F) within 7 days of vaccination considered related;  
• 
Occurence of grade ≥3 adverse events that lasted at least 48 h and associated with vaccination, 
and for which there is no alternative feasible explanation, in more than 20% of participants 
(except local reactions: pain/tenderness, erythema/redness, and induration/swelling) after 
primary or booster inoculation; 
• 
Occurence of grade ≥3 clinical laboratory abnormality related adverse events with clinical 
manifestations, that not recovered for at least 8 days and associated with vaccination, and for 
which there is no alternative feasible explanation, in more than 20% of participants after 
primary or booster inoculation. 
Approval from the SRC will be required prior to any further vaccination in the affected cohort. 
The SRC may call for the opening of a lower dose level cohort. 
The same events will prompt IMP discontinuation for individual subjects as described in Section 
6.9 until SRC review is completed.  
6.7 Criteria for delay of boost vaccination and/or stop for boost vaccination 
After enrollment, subjects may encounter clinical circumstances that warrant a delay in the 
administration of the subsequent vaccination of investigational vaccine/placebo. These situations 
are listed below:  
• 
Individuals with a clinically significant active infection (as assessed by the investigator) or 
axillary temperature ≥37.3°C or oral temperature ≥38.0°C, within 3 days before intended 
investigational vaccine/placebo vaccination. Or other clinical symptoms/diseases that may be 
considered inappropriate for vaccination by the investigator 
• 
Individuals who received any other vaccines within 21 days before planned vaccination.  
If a subject meets a criterion for delay of vaccination, the subject may receive trial vaccination, if 
the subject is otherwise eligible for trial participation even if the window period of vaccination 
visit has passed. The decision to vaccinate in those situations will be taken by the investigator.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 55 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
In this trial, the second vaccination may be stopped in some circumstances. These circumstances 
include systemic anaphylaxis or severe hypersensitivity reactions following the prime 
vaccine/placebo administration. If these reactions occur, the subject must not receive additional 
vaccinations; however, the subject is encouraged to continue in trial participation for safety reasons.  
6.8 Criteria for early study termination of a subject  
Under some circumstances, a subject’s trial participation may be terminated early. This means that 
no further trial procedures (including data collection) will be performed on that subject beyond 
the specific date of early termination. The primary reason for early termination of the subject from 
the trial should be recorded in the electronic Case Report Form (eCRF “end of study visit” page) 
using the following categories. For screen failure subjects, refer to Section 9.1.11.  
1. Safety stopping criteria: The SRC will review and evaluate the collected safety data 
periodically during the trial. A decision to stop treatment for an individual subject or to 
terminate the trial may be taken if safety concerns are identified by the SRC. Suspected 
unexpected serious adverse reactions (SUSARs) will immediately be reviewed by the SRC. 
They will trigger a temporary stop of IMP administration to new subjects in the respective dose 
level cohort for that vaccine until the SRC recommendation to continue or to permanently stop 
IMP administration of new subjects in the respective dose level cohort for that vaccine.  
2. Adverse events: the subject has experienced an AE (irrespective of being related to the trial 
vaccine or trial-related procedures) that requires early termination because continued 
participation imposes an unacceptable risk to the subject’s health and / or the subject is 
unwilling to continue participation because of the AE. If the subject is unwilling to continue 
because of the AE the primary reason for early termination in this case will be ‘withdrawal due 
to AE’ and not ‘withdrawal of consent’, see below. Any ongoing AEs leading to early 
termination will be followed by the investigator until resolution or stabilization.  
3. Lost to follow up: the subject did not return to the study site and several attempts to contact 
the subject were unsuccessful. Attempts to contact the subject must be documented.  
4. Withdrawal of consent: the subject wishes to withdraw from the trial. The primary reason for 
early termination will be ‘withdrawal of consent” if the subject withdraws from participation 
due to a non-medical reason (ie, reason other than AE). The reason for withdrawal, if provided, 
should be recorded in the eCRF.  
Note: all attempts should be made to determine the underlying reason for the withdrawal and, 
where possible, the primary underlying reasons should be recorded.   
5. Premature study termination by Fosun, a regulatory agency, the IEC/IRB, or any other authority.  
If the clinical study is early terminated by the Fosun, the investigator is to promptly inform the 
subjects and local EC/IRB and should assure appropriate follow up for the subjects. The primary 
reason for early termination in this case will be ‘trial termination”.  
6. Subject’s death during trial participation.  
7. Other.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 56 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Note: the specific reasons should be recorded in the “specify” field of the eCRF.  
6.9 Criteria for premature discontinuation of trial vaccine application   
Early (premature) study termination of a subject will by default prevent the subject from continued 
Trial Vaccine administration, as the subject will no longer be participating in the study.  
In addition to early termination (see Section 6.8) criteria, other situations may apply in which 
subjects may continue participating in the trial (eg, contributing safety data according to protocol) 
but Trial Vaccine application is discontinued selectively. Regardless of the reasons for 
discontinuation of Trial Vaccine application, this must be documented as protocol deviation. Even 
if the subject is deemed ineligible to continue to receive Trial Vaccine, all efforts should be made 
to continue the collection of safety data according to protocol. In addition, the one primary reason 
for early discontinuation of Trial Vaccine application should be recorded in the eCRF, “end of Trial 
Vaccine application” page using the following categories.  
1. Adverse events: the subject has experienced an AE (irrespective of being related to the Trial 
Vaccine or trial-related procedures) for which subsequent Trial Vaccine applications impose an 
unacceptable risk to the subject’s health, but the subject will continue trial participation or 
other study procedures for safety.   
2. Lost to follow up: the subject did not return to the clinical and several attempts to contact the 
subject were unsuccessful. Attempts to contact the subject must be documented  
3. Withdrawal of consent: the subject wishes to withdraw from the trial. The primary reason for 
early termination will be ‘withdrawal of consent” if the subject withdraws from participation 
due to a non-medical reason (ie, reason other than AE). The reason for withdrawal, if provided, 
should be recorded in the eCRF.  
4. Premature study termination by Fosun, a regulatory agency, the IEC/IRB, or any other authority.  
If the clinical study is early terminated by the Fosun, the investigator is to promptly inform the 
study subjects and local EC/IRB and should assure appropriate follow up for the subjects. The 
primary reason for early termination in this case will be ‘trial termination”.  
5. Subject’s death during trial participation.  
6. Protocol Deviation: a protocol deviation is any change, divergence, or departure from the study 
design or procedures of a study protocol. The subject may remain in the trial unless 
continuation in the trial jeopardizes the subject’s health, safety, or rights (see Section 7.4).  
7. Pregnancy: any subject who, despite the requirement for adequate contraception, becomes 
pregnant during the trial will not receive further Trial Vaccine applications. Pregnant subjects 
should, however, be asked to continue participating in the trial contributing data to the safety 
follow-up according to protocol. In addition, the site should maintain contact with the pregnant 
subject and complete a “Clinical Trial Pregnancy Form” as soon as possible. The subject should 
be followed-up until the birth of the child, or spontaneous or voluntary termination; when 
pregnancy outcome information becomes available, the information should be captured using 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 57 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
the same form. Data obtained from the “Clinical Trial Pregnancy Form” will be captured in the 
safety database.  
8. Other.  
Note: the specific reasons should be recorded in the “specify” field of the eCRF.

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 58 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
6.10. Premature termination or suspension of the trial  
6.10.1 Criteria for premature termination or suspension of the trial  
The trial will be completed as planned unless one or more of the following criteria are satisfied 
that require temporary suspension or early termination of the trial.  
• 
New information or other evaluation regarding the safety or efficacy of the investigational 
vaccine that indicates a change in the known risk/benefit profile, such that the risk/benefit is 
no longer acceptable for subjects participating in the trial.  
• 
SRC/IDMC recommends that the trial should be suspended or terminated.  
• 
It deviates from Good Clinical Practice (GCP) significantly, so that the primary objective of 
the trial cannot be achieved or the safety of subjects may be compromised.  
6.10.2 Procedures for premature termination or suspension of the trial  
If the Fosun, an institutional review board (IRB)/independent ethics committee (IEC) or 
regulatory authority elects to terminate or suspend the trial or the participation of an 
investigational site, a trial-specific procedure for early termination or suspension will be provided 
by the Fosun.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 59 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
7.0 Inclusion and exclusion criteria   
All entry criteria, including test results, need to be confirmed prior to randomization.  
7.1 Inclusion and exclusion criteria for adults  
Inclusion criteria:  
1. Male or female subjects of ≥18 years old and ≤55 years old with body mass index (BMI) ≥18 
and ≤30 at the Screening Visit.   
2. Individuals who are in good health condition at the time of entry into the trial as determined 
by medical history, physical examination (including vital signs, ECG) and eligibility screening 
test (hematology, blood chemistry and urine analysis) and clinical judgment of the investigator 
at Screening Visit.   
3. The subject can provide with imformed consent and signs and dates a written informed consent 
form (ICF) prior to the initiation of any trial procedures. 
4. They must be able to understand and follow trial-related instructions.  
5. They must be willing and able to comply with planned visits, treatment schedule, laboratory 
tests and other requirements of the trial.  
6. Negative in antibodies screening of SARS-CoV-2 (fingerstick). 
7. Normal in chest CT scans (no imaging features of COVID-19). 
8. Axillary temperature≤37.0ºC. 
9. Negative SARS-CoV-2 test in throat swabs by RT-PCR. 
10. Women of childbearing potential (WOCBP) must have a negative serum β-hCG at Screening 
Visit. Women that are postmenopausal (Menopause ≥12 consecutive months) or permanently 
sterilized will be considered as not having reproductive potential.  
11. WOCBP must have used effective contraception 14 days prior to screening and agree to use 
effective contraception continuously during the trial period, from 14 days prior to Screening 
Visit to 60 days after the last immunization.  
12. WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction 
during trial, starting from Screening Visit and continuously until 60 days after be given the 
last immunization.  
13. Men who are sexually active with a WOCBP and have not had a vasectomy must agree to 
practice a effective form of contraception with their female partner of childbearing potential 
during the trial, starting from Screening Visit and continuously until 60 days after be given the 
last immunization.  
14. Men must be willing to refrain from sperm donation, starting from Screening Visit and 
continuously until 60 days after receiving the last immunization.  
Exclusion criteria:    

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 60 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
1. Have had any acute illness, as determined by the investigator, with or without fever, within 72 
h prior to the prime vaccination. 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.  
2. Are breastfeeding on the day of Screening Visit or who plan to breastfeed during the trial, 
starting from Screening Visit and continuously until at least 90 days after the last immunization. 
Women or partners who plan to become pregnant within 1 year post the screening visit. 
3. Have a known allergy, hypersensitivity, or intolerance to the planned vaccine for trial 
including any excipients.  
4. Used to have a history of hypersensitivity or serious reactions to vaccinations. 
5. Received any vaccination within 4 weeks prior to Visit 1.  
6. Don't agree to not be vaccinated during the trial, starting from Screening Visit and 
continuously until 28 days after receiving the last immunization, except emergency 
vaccination (e.g. rabies vaccine, tetanus vaccine). 
7. Had any medical condition (e.g., autoimmune disease) 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.  
8. Have any surgery planned during the trial, starting from Screening Visit and continuously until 
at least 90 days after the last immunization.  
9. Had any chronic use (more than 14 continuous days) of any systemic medications, including 
immunosuppressant or other immune-modifying drugs, within 6 months prior to Screening 
Visit unless in the opinion of the investigator, the medication would not prevent, limit, or 
confound the protocol-specified assessments or could compromise safety of subjects.  
10. Had administration of any immunoglobulins and/or any blood products within the 3 months 
prior to Screening Visit.  
11. Had administration of another investigational product including vaccines within 60 days or 5 
half-lives (whichever is longer), prior to Screening Visit.  
12. With known history of AIDS or HIV test positive.  
13. Have active HBV or HCV infection, through medical inquiry.  
14. History of SARS, SARS-CoV-2 or MERS infection. Suspected SARS patients should be 
screened for SARS antibodies. 
15. Previously participated in a clinical trial involving lipid nanoparticles.  
16. Are subject to exclusion periods of other clinical trials or simultaneous participation in another 
clinical trial.  
17. Have any affiliation with the study site (e.g., are close relative of the investigator or dependent 
person, such as an employee or student of the study site).  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 61 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
18. Have a history of drug abuse or known medical, psychological or social conditions within the 
past 5 years. In the opinion of the investigator, could comprise their well-being if they 
participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-
specified assessments.  
19. Have a history of narcolepsy.  
20. Have history of alcohol abuse or drug addiction within 1 year prior to Screening Visit.  
21. Have a history of or suspected immunosuppressive condition, acquired or congenital, as 
determined by medical history and/or physical examination at Screening Visit.  
22. Have any abnormality or permanent body art (e.g., tattoo), in the opinion of the investigator, 
would obstruct the ability to observe local reactions at the vaccination site.  
23. Have had any blood loss >400 mL, e.g., due to donation of blood or blood products or injury, 
within the 28 days prior to Screening Visit or plan to donate blood or plasma during the trial, 
starting from Screening Visit and continuously until at least 28 days after be given the last 
immunization.  
24. Travel or live in any country or region with a high SARS-CoV-2 infection risk (as defined at 
Screening Visit) within the 14 days prior to Screening Visit.  
25. They plan to visit any country or region with a high SARS-CoV-2 infection risk (as defined at 
Screening Visit), from Screening Visit until 14 days after be given the last immunization.  
26. Symptoms of COVID-19, e.g., respiratory symptoms, fever, cough, shortness of breath and 
breathing difficulties.  
27. Have had contact with confirmed COVID-19 patients or persons tested positive for SARS-
CoV-2 within the 30 days prior to Screening Visit.  
28. Are vulnerable persons, e.g., soldiers, subjects in detention, CRO or Fosun staffs or their 
family members. 
7.2 Inclusion and exclusion criteria for the elderly  
Inclusion criteria: 
1. Male or female subjects ≥65 years old and ≤85 years old at Screening Visit.   
2. Individuals who are in a health condition that can receive the investigational vaccine, at the 
time of entry into the trial as determined by medical history, physical examination (including 
vital signs, ECG) and eligibility screening tests (hematology, biochemistry and urinalysis) and 
clinical judgment of the investigator at Screening Visit.   
3. The subject can provide with informed consent and signs and dates a written informed consent 
form (ICF) prior to the initiation of any trial procedures. 
4. They must be able to understand and follow trial-related instructions.  
5. They must be willing and able to comply with planned visits, treatment schedule, laboratory 
tests and other requirements of the trial.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 62 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
6. Negative in antibodies screening of SARS-CoV-2 (blood sample from fingertip). 
7. No imaging features of COVID-19 in chest CT scan. 
8. Axillary temperature≤37.0ºC. 
9. Negative SARS-CoV-2 test in throat swabs by RT-PCR. Women of childbearing potential 
(WOCBP) must have a negative serum β-hCG at Screening Visit. Women that are 
postmenopausal (Menopause≥12 consecutive months) or permanently sterilized will be 
considered as not having reproductive potential.  
10. Women of childbearing potential (WOCBP) must have a negative serum β-hCG at Screening 
Visit. Women that are postmenopausal (Menopause ≥12 consecutive months) or permanently 
sterilized will be considered as not having reproductive potential.  
11. WOCBP must have used effective contraception 14 days prior to screening and agree to use 
effective contraception continuously during the trial period, from 14 days prior to Screening 
Visit to 60 days after the last immunization.  
12. WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction 
during trial, starting from Screening Visit and continuously until 60 days after be given the last 
immunization.  
13. Men who are sexually active with a WOCBP and have not had a vasectomy must agree to 
practice a effective form of contraception with their female partner of childbearing potential 
during the trial, starting from Screening Visit and continuously until 60 days after be given the 
last immunization.  
14. Men must be willing to refrain from sperm donation, starting from Screening Visit and 
continuously until 60 days after receiving the last immunization. 
Exclusion criteria:    
1. Physical examination and qualifying screening during screening visits, finding baseline 
laboratory abnormalities ≥grade 3 (for hematology abnormalities with Grade ≥2, according to 
grading criteria in Appendix B). 
2. Have had any acute illness, as determined by the investigator, with or without fever, within 72 
h prior to the prime vaccination. 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 not prevent, limit, or confound the protocol-specified assessments.  
3. Have a known allergy, hypersensitivity, or intolerance to the planned vaccine for trial 
including any excipients.  
4. Used to have a history of hypersensitivity or serious reactions to vaccinations. 
5. Received any vaccination within 4 weeks prior to Visit 1. 
6. The subject doesn't agree to avoid vaccination during the trial, starting from Screening Visit 
and continuously until 28 days after receiving the last immunization, except emergency 
vaccination (e.g. rabies vaccine, tetanus vaccine). 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 63 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
7. Had administration of any immunoglobulins and/or any blood products within the 3 months 
prior to Screening Visit. 
8. Had any serious or life-threatening medical condition (e.g., autoimmune disease, 
cardiovascular disease) 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. 
9. Have any surgery planned during the trial, starting from Screening Visit and continuously until 
at least 90 days after the last immunization.  
10. Had any chronic use (more than 14 continuous days) of any systemic medications, including 
immunosuppressant or other immune-modifying drugs, within 6 months prior to Screening 
Visit unless in the opinion of the investigator, the medication would not prevent, limit, or 
confound the protocol-specified assessments or could compromise safety of subjects.  
11. Had administration of another investigational product including vaccines within 60 days or 5 
half-lives (whichever is longer), prior to Screening Visit.  
12. With known history of AIDS or HIV test positive.  
13. Have infection history of HBV or HCV.  
14. History of SARS, SARS-CoV-2 or MERS infection. Suspected SARS patients should be 
screened for SARS antibodies. 
15. Previously participated in a clinical trial involving lipid nanoparticles.  
16. Are subject to exclusion periods of other clinical trials or simultaneous participation in another 
clinical trial.  
17. Have any affiliation with the study site (e.g., are close relative of the investigator or dependent 
person, such as an employee or student of the study site).  
18. Have a history of drug abuse or known medical, psychological or social conditions within the 
past 5 years. In the opinion of the investigator, could comprise their well-being if they 
participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-
specified assessments.  
19. Have a history of narcolepsy.  
20. Have history of alcohol abuse or drug addiction within 1 year prior to Screening Visit. 
21. Have a history of or suspected immunosuppressive condition, acquired or congenital, as 
determined by medical history and/or physical examination at Screening Visit.  
22. Have any abnormality or permanent body art (e.g., tattoo), in the opinion of the investigator, 
would obstruct the ability to observe local reactions at the vaccination site.  
23. Have had any blood loss >400 mL, e.g., due to donation of blood or blood products or injury, 
within the 28 days prior to Screening Visit or plan to donate blood or plasma during the trial, 
starting from Screening Visit and continuously until at least 28 days after be given the last 
immunization. 
24. Travel or live in any country or region with a high SARS-CoV-2 infection risk (as defined at 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 64 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Screening Visit) within the 14 days prior to Screening Visit.  
25. They plan to visit any country or region with a high SARS-CoV-2 infection risk (as defined at 
Screening Visit), from Screening Visit until 14 days after be given the last immunization.  
26. Symptoms of COVID-19, e.g., respiratory symptoms, fever, cough, shortness of breath and 
breathing difficulties.  
27. Have had contact with confirmed COVID-19 patients or persons tested positive for SARS-
CoV-2 nucleic acids or antibodies within the 30 days prior to Screening Visit. 
28. Are vulnerable persons, e.g., soldiers, subjects in detention, CRO or Fosun staffs or their 
family members. 
 
8.0 VACCINATION AND MANAGEMENT OF VACCINE  
This section contains the information of the investigational drug needed for the protocol, including 
vaccination and management of vaccine.  
8.1 Vaccination 
8.1.1 Investigational vaccine/ placebo  
Investigational vaccine:  
The drug product is a preservative-free, sterile dispersion of RNA formulated in lipid nanoparticles 
(LNP) in aqueous cryoprotectant buffer for intramuscular administration. The RNA drug substance 
is the only active ingredient in the drug product. For dispensing and operation protocol, see 
Pharmacy Manual. 
Frequency of 
vaccination:  
Two injections (21 days apart).  
Route of vaccination:  
Intramuscular (IM); upper arm, musculus deltoideus; the P/B regimens. 
The same arm may be used for both immunizations. The non-dominant 
arm is preferred.  
Placebo:  
NaCl 0.9% solution is being used as placebo. It is a sterile, clear, colorless liquid solution of sodium 
chloride without preservative designed for parenteral use only. The placebo is commercially 
available packaged and stored according to the labelling. The placebo is vaccinated by IM at 21-
day intervals. 
8.1.2 Preparation/handling/storage/accountability  
The preparation of solution for injection will be carried out by the pharmaceutical professionals 
or other trained personnel at the trial site according to the sterile operation procedures. 
For instructions on preparation, handling and storage of investigational drugs (IMP BNT162b1 
vaccine), see the Pharmacy Manual. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 65 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all IMP received and any discrepancies are reported and resolved 
before use of IMP. 
Only subjects enrolled in the trial may receive IMP and only authorized site unblinded personnel 
may administer IMP. All IMP (and any components thereof) must be stored in a safe, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized study site 
personnel. 
The investigator, study site, or the head of the site (where applicable) is responsible for storage, 
checking, and record maintenance (i.e., receipt, check and final disposition records) of IMP (and 
any components thereof). 
Further guidance and information for the final disposition of unused IMP (and any components 
thereof) is provided in the Pharmacy Manual. 
8.1.3 Dose and regimen  
Each randomized subject will receive BNT162b1 (low-dose and high-dose) or placebo 
intramuscularly (IM) for two times – one injection at Visit 1 (on Day 1) and one injection at Visit 
5 (on Day 22) IM into the one third of the deltoid muscle, preferably in the non-dominant arm.The 
additional doses may be explored, and the details will be provided in the pharmacy manual  
Planned cohorts:  
• 
Cohort 1: BNT162b1 low-dose (10 µg); 
• 
Cohort 2: BNT162b1 high-dose (30 µg); 
• 
Cohort 3: placebo. 
8.2 Allocation, preparation and injection procedures of investigational vaccine/placebo  
According to the instructions of the Pharmacy Manual, the designated qualified non-blind 
personnel shall regulate, prepare and inject investigational vaccine/ placebo. All investigational 
vaccine/placebo preparation will be documented.  
The investigator or designee will be responsible for overseeing the administration of 
investigational vaccine/placebo to subjects enrolled in the trial according to the procedures 
stipulated in this trial protocol.  
Standard immunization practices are to be observed and care should be taken to administer the 
injection intramuscularly. Before administering the vaccine, the vaccination site is to be 
disinfected with a skin disinfectant (eg, 70% alcohol). And allow the skin to dry.  
As with all injectable vaccines, trained medical personnel and appropriate medical treatment 
should be readily available in case of anaphylactic reactions following vaccination.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 66 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
8.3 Randomization code creation and storage  
The method of block randomization will be used, and the random table of subjects will be 
generated by an independent randomized professional through SAS9.4 or above, and will be 
imported to the interactive response technology (IRT) system, which could only be accessed by 
authorized personnel. Subjects, researchers and sponsor study management will remain blinded 
throughout the trial. The authorized unblinded staff of the research center can obtain the subject 
allocation information through the IRT system and allocate the experimental vaccine or placebo of 
the corresponding group according to the allocation information. 
All selected subjects will be assigned a screening number. For the selected subjects, the IRT system 
was used for randomization and a random number was obtained (the random number was used as 
the unique subject ID number). The random parameters and Settings are described in detail in the 
randomization specification. 
8.4 Maintain of blinding  
The trial is a blinding study for subjects and observers. The subjects, data collectors (eg, 
investigator), and data evaluators (eg, trial statisticians) are blinded. The investigational product 
assignment will be maintained by the unblinded site staff designee. It is no need of blinding for 
investigational products. 
All care must be taken to ensure that the unblinded reports and documents are shared only with 
unblinded personnel and properly stored in a secured area, accessible only by authorized personnel. 
All non-blinded personnel, including dispensers and vaccination nurses, are required to sign 
confidentiality agreements. 
8.5 Unblinding procedures  
The investigational vaccine/placebo blind shall not be broken by the investigator unless 
information concerning the investigational vaccine/placebo is necessary for the medical treatment 
of the subject. In the event of a medical emergency, if possible, the medical monitor should be 
contacted before the investigational vaccine/placebo blind is broken to discuss the need for urgent 
unblinding.  
The Fosun’s Pharmacovigilance Department must be notified as soon as possible if the 
investigational vaccine/placebo blinding is broken by the investigator; and if the unblinding was 
for medical reasons (SAE), the completed SAE form must be sent within 24 hours (ie, follow the 
standard process for reporting of SAEs). The date, time, and reason the blind is broken must be 
recorded in the source document and the same information (except the time) must be recorded on 
the eCRF.  
 Unblinding will be occurred at the initial analysis of safety and immunogenicity 28 days after 
boost vaccination, but the subjects will be kept blinded. 
  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 67 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
9.0 TRIAL PLAN  
9.1 Trial procedures  
The following sections describe the trial procedures and data to be collected. For each procedure, 
subjects are to be assessed by the same investigator or site personnel whenever possible. The 
Schedule of Trial Procedures is located in Table 2.  
9.1.1 Informed consent  
Informed consent must be obtained at Screening Visit, prior to the subject entering into the trial 
and before any protocol-directed procedures are performed.  
A screening number will be assigned at Screening Visit to each subject after informed consent is 
obtained. If all eligibility criteria are fulfilled, a randomization number (the unique subject ID 
number) will be assigned, and this subject ID number will be used throughout the trial. Subject 
screening numbers assigned to subjects who fail screening should not be reused (Section 9.1.10).  
9.1.2 Demographics, medical history, travel history, prior/concomitant 
medications/vaccinations, and blood donation  
Demographic information, to be obtained at Screening Visit, will include age (date of birth), sex, 
race, and ethnicity as provided by the subject. See Section 6.1 for more details about the enrollment.  
Medical history will also be collected at Screening Visit and at Visit 1 (Day 1) pre-vaccination and 
will include any medical history that may be relevant to subject eligibility for trial participation 
such as prior vaccinations, concomitant medications, and previous and ongoing illnesses or 
injuries. Relevant medical history can also include any medical history that contributes to the 
understanding of an AE that occurs during trial participation, if it represents an exacerbation of an 
underlying disease/preexisting problem.  
Medical occurrences before administration of the first dose of investigational vaccine/placebo are 
considered medical history.  
Travel history to SARS-CoV-2 endemic countries and SARS-CoV-2 endemic regions of China 
within 2 weeks prior to screening will be collected at Screening Visit. Travel history to SARS-
CoV-2 endemic countries and SARS-CoV-2 endemic regions of China will be collected at each 
visit.  
Ask the subject’s medical history, record the following medication of the subject: 4 weeks within 
the vaccincation, long-term use of systemic medication affecting the immune function within 6 
months, immunoglobulin and/or blood products within 3 months, take another kind of study drug 
(including vaccine) within 60 days or five half-life (will be subject to a long time). And all 
medications, vaccines and blood products taken or received by the subjects within 1 monthprior 
to the start of the trial are to be recorded on the source document (patient record) and entered on 
the Prior and Concomitant Medications eCRF. The use of antipyretics and/or analgesic 
medications within 24 hours prior to vaccination must be identified and the reason for their use 
(prophylaxis versus treatment) must be described in the source documents and the eCRF.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 68 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Contradicted medication/treatment (See Section 7.0)  
• 
Had any chronic use (more than 14 continuous days) of systemic medications affecting 
immune function, including immunosuppressant or other immune-modifying drugs, within 6 
months prior to Screening Visit unless in the opinion of the investigator, the medication would 
not prevent, limit, or confound the protocol-specified assessments or could compromise safety 
of subjects. 
• 
Received any vaccine within 4 weeks prior to Visit 1.  
• 
Had administration of any immunoglobulins and/or any blood products within the 3 months 
prior to Screening Visit.  
• 
Had administration of another investigational product including vaccines within 60 days or 5 
half-lives (whichever is longer), prior to Screening Visit.  
Subjects should not donate blood during the main study period (starting after screening visit and 
continuously until at least 28 days after receiving the last immunization).   
Medical history (including corresponding medication) to be obtained will include any significant 
conditions or diseases that have disappeared or resolved at or prior to signing of informed consent.  
9.1.3 SARS-CoV-2 testing  
All subjects will be tested for SARS-CoV-2 at Screening Visit, including oropharyngeal swabs 
through RT-PCR and fingertip blood will be collected for SARS-CoV-2 antibodies screening.  
The anti-SARS-CoV-2 antibody testing will be performed with a commercially available antibody 
test. It will be used to test subjects who may have experienced enhanced respiratory disease or 
progression of flu-like symptomatology, such as non-resolution of the symptoms after 7 d, 
symptom kinetics that are inconsistent with a relationship to RNA immunization, as might be 
expected with a COVID-19 disease (See Section 10.5). 
9.1.4 Physical examination  
The physical examination must be carried out by qualified health professionals in accordance with 
the relevant regulations and the licensing requirements designated with the “Site Authorization 
Form”. Complete physical examination, including height, will be performed at Screening Visit 
according to the investigator’s standard practice. Measurement of height is only required at 
Screening Visit. BMI will be calculated using standard BMI calculator.  
Additional symptom-directed physical examinations may be performed at following visits if 
deemed necessary or indicated by review of the subject’s medical history, and should assess 
clinically significant changes from the baseline examination.  
The following should be documented in the subject’s source document and transcribed into the 
eCRF:  
• 
The findings of complete physical examinations;  
• 
the findings of symptom-directed physical examinations;  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 69 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
• 
if symptom-directed physical examinations were not required.  
9.1.5 Vital signs, 12-lead ECG and chest CT scan  
Vital signs include systolic/diastolic blood pressure, pulse rate, respiratory rate, and body 
temperature. Measurement of body weight is only required at Screening Visit. Follow standard of 
care for trial population and operational feasibility.   
Vital signs must be within normal limits (ie, below Grade 1 as specified in the NMPA Toxicity 
Grading Scale for Healthy Adult Volunteers, see Appendix B).   
12-lead ECG and Chest CT scan will be performed at Screening Visit. Chest CT images must have 
no imaging features of COVID-19. 
In the event of abnormal ECG, heart rate or blood pressure due to physiological variation or activity, 
the subject may rest for 10 minutes in a quiet room, and then ECG, blood pressure and/or heart 
rate may be re-measured. Repeated ECG or vital signs may be used to determine eligibility.   
9.1.6 Blood sample and urine sample collection  
Blood samples will be collected at each site visit: ie, at Screening Visit for eligibility screening 
tests (clinical laboratory testing, see Section 9.1.6.3), at Visits 2, 3 and 6 for routine safety 
laboratory testing (see Section 9.1.6.4 for Visits 2, 6 coagulation function test, Visits 2, 6, 11 
thyroid function test). Blood samples for immunogenicity (anti-S1/ anti-RBD IgG and SARS-CoV-
2 neutralizing antibody) will be collected at Visits 1, 5, 6, 8, 10, 11 and 12 for adults and at Visits 
1, 5, 6, 8, 11 and 12 for the elderly (see Section 9.1.6.5). 
 
 
 
 Should a blood sampling be 
performed during a vaccination visit, this sampling must occur before the injection of the 
investigational vaccine or placebo. Serum sample will be collected for women of childbearing 
potential at Screening Visit and Visit 5 before each investigational vaccine/placebo injection for 
pregnancy testing (see Section 9.1.9). Figertip blood samples will be collected at Screening Visit 
for SARS-CoV-2 serostatus determination (see Section 9.1.6.1) and HIV serostatus determination 
(see Section 9.1.6.2). 
Urine samples will be collected for all subjects at Screening Visit for eligibility screening (see 
Section 9.1.6.3), and at Visits 2, 3 and 6 for routine safety laboratory testing (see Section 9.1.6.4).  
All samples will be collected in accordance with acceptable laboratory procedures. Samples of 
immunogenicity and CMI testing will be processed and stored at the study site as described in the 
provided Laboratory Manual.  
9.1.6.1 SARS-CoV-2 antibody test  
All subjects who sign the ICF will be tested for SARS-CoV-2 antibody test (fingertip blood) at 
Screening Visit.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 70 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
9.1.6.2 HIV test  
All subjects who sign the ICF will be tested for HIV antibody at Screening Visit. For screening, 
the subject’s fingertip blood will be collected for anti-HIV antibodies.  
9.1.6.3 Screening laboratory testing  
Screening laboratory testing that will be performed on blood and urine samples at Screening Visit 
are outlined in Table 4.   
Subjects of adults must have laborat ory values within normal limits or not be above Grade 1 as 
defined in Appendix B within 7 days before enrollment, and Grade 2 for the elderly. If the results 
of laboratory screening testing are out of acceptable range, repeat of screening tests is permitted 
once, provided there is an alternative explanation for the out of normal range value.  
Should the respective repeated test results be available within the screening period, no new subject 
screening numbers will be required; the repeated screening tests will be recorded in the appropriate 
CRF (unscheduled lab form). Should the respective repeated test results not be available within 
the screening period, the subject would need to be screen failed and all screening procedures and 
tests would need to be repeated with a new subject screening number.  
Blood samples for screening laboratory testing will be approximately 15 mL.   
Table 3  Clinical laboratory assessments  
Sample  
Test  
Blood  
Hematology  
hemoglobin, hematocrit, red blood cell count, white blood cell count and 
differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), 
platelet count 
Blood chemistry  alkaline phosphatase, creatinine, ferritin, C-reactive protein, albumin, 
alanine aminotransferase, amylase, aspartate aminotransferase, gamma 
glutamyl transpeptidase, total bilirubin, blood urea, fasting blood sugar, 
lipase, sodium, potassium, calcium 
Thyroid function triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone. 
Coagulation 
function 
prothrombin time (PT), activated partial thromboplastin time (APTT), 
thrombin time (TT)), fibrinogen (FIB). 
Pregnancy test  
β-hCG test  
Urine  
Urinalysis  
glucose, bilirubin, ketone, specific gravity, occult blood, pH, protein, 
urobilinogen, nitrite, and leukocytes. Microscopic urinalysis if warranted by 
dipstick results, urine sediment will be microscopically examined for the 
presence of red blood cells, white blood cells, casts, crystals, epithelial cells, 
and bacteria. 
9.1.6.4 Safety laboratory testing   
Routine safety laboratory testing includes hematology, blood chemistry and urine routines, thyroid 
function and coagulation function and laboratory testing is outlined in Table 3. Each blood sample was 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 71 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
approximately: blood routine 2 ml, blood chemistry 4 ml, ferritin 4 ml, thyroid function 3 ml, 
coagulation function 2ml.  
9.1.6.5 Immunogenicity assessment  
Serum immunogenicity (humoral immunity / antibody) is detected by ELISA and neutralizing 
antibody test. Each blood sample for ELISA assessments will be approximately 7.5 mL, and for 
neutralizing antibody test will be approximately 7.5 mL. 
Should a blood sampling be performed during a vaccination visit, this sampling must occur before 
the vaccination of the investigational vaccine or placebo.  
9.1.6.6 CMI assessments  
 
 
 
 
9.1.7 Safety assessments  
During the trial, safety assessments will include collection and recording of local (vaccination site) 
and systemic reactions (including fever), unsolicited AEs (serious and non-serious). Refer to 
Section 10.1 for safety definitions. Details on collection and reporting of reactions and AEs are in 
Section 10.2. Refer to Section 9.3.4 for details about the diary cards distribution, review and 
collection processes.  
9.1.8 Contraception guidance  
Subjects will be provided with guidelines on acceptable methods of contraception.  
Female subject of childbearing potential and sexually active will have to use an “acceptable 
contraceptive method” from 2 weeks before screening through 2 months after the last dose of trial 
vaccine, and will be advised not to donate ova during this period.  
Male subjects must be advised not to donate sperm during this period.  
9.1.9 Pregnancy  
For WOCBP, pregnancy testing will be performed at Screening Visit, and blood pregnancy testing 
will be performed before the boost vaccination of investigational vaccine/placebo.   
Subjects must have a negative serum β-hCG pregnancy test at screening and before boost 
vaccination.  
For the sake of the safety of a subject, if a female subject or female partner of a male subject is 
pregnant during the study vaccination, it must be reported to the Fosun with a pregnancy reporting 
form A within 24 hours after learning the event. At the same time, the pregnant patient must be 
followed up to determine the pregnancy outcome (provided that the female partner of a male 
subject agrees to have the data collected), including spontaneous or induced abortion, details of 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 72 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
childbirth, congenital malformations, or maternal or neonatal comorbidities, etc., and a pregnancy 
reporting form B will be filled for reporting. 
Normal deliveries should be followed up at least one year after birth; other pregnancy results must 
be reported as serious adverse events (SAE), and the SAE form must be completed and reported, 
in addition to the pregnancy report form. Selective abortion without complications is not 
considered as an adverse event. If other SAEs occur during pregnancy, the SAE form must also 
be completed and reported. 
If the subject becomes pregnant during the trial, she will not receive any further doses of any 
investigational vaccine/placebo. Should the pregnancy occur after administration of investigational 
vaccine/placebo in a blinded condition, the investigator must inform the subject of their right to 
receive information on the investigational vaccine/placebo injected. If the subject chooses to know 
unblinded information, the individual blind should be broken by the investigator and procedures 
must be followed, as described in Section 8.5.  
9.1.10 Documentation of trial entrance/randomization  
Only subjects who have signed an ICF at Screening Visit, meet all of the inclusion criteria and 
none of the exclusion criteria, are eligible for allocation/randomization into the vaccination phase.  
One single subject screening number will be assigned to each subject at Screening Visit. In the 
study, subjects will be randomized at 1:1:1 with each cohort of 24 subjects to inject BNT162b1 or 
placebo.  
9.1.11 Documentation of subjects who are not enrolled/randomized  
If a subject who signs the ICF is found to be not eligible within the screening period, the 
investigator should complete the eCRF and explain the reasons. 
The primary reason for un-enrollment/non-randomization is recorded in the eCRF using the 
following categories:  
• 
Screen failure: does not meet one or more inclusion criteria; does meet one or more exclusion 
criteria;  
• 
Withdrawal by subject;  
• 
Trial terminated by Fosun Phar.  
A subject may be a temporary screen failure under the following circumstances: due to temporary 
conditions such as receipt of immunosuppressive or immunomodulatory therapies, blood products, 
immunoglobulins, or vaccines, in the respective prohibited periods (see exclusion criteria), or in 
the event that a subject has an indeterminate pregnancy test result. Subjects screen failed for the 
above-mentioned reasons may be rescreened once they cease to meet the respective exclusion 
criteria. Should the respective repeated test results be available within the prime screening period, 
no new subject screening numbers will be required; the repeated screening tests will be recorded 
in the appropriate CRF (unscheduled visit form). Should the respective repeated test results not 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 73 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
be available within the prime screening period, the subject would need to be screen failed and all 
screening procedures and tests would need to be repeated with a new subject screening number.  
Subject screening numbers assigned to subjects who fail screening should not be reused.  
9.2 Subject treatment compliance  
The investigator records all injections of investigational vaccine/placebo given to the subject in 
the eCRF.  
9.3 Schedule of observations and procedures  
The schedule for all trial-related procedures for all evaluations is shown in Table 2. Assessments 
should be completed at the designated visit(s)/time point(s).  
9.3.1 Screening procedures (Screening Visit)  
See Section 6.1 for more details about the enrollment.  
The following screening procedures will be performed at Screening Visit:  
1. Confirm informed consent, and complete and collect ICF (see Section 9.1.1). Before 
performing any other trial procedure, the signed ICF needs to be obtained. Only applicable for 
newly screened subjects.  
2. Assign subject ID number (see Section 6.1 for more details about the enrollment).   
3. Assess eligibility criteria (see Sections 7.1 and 7.2).  
4. Collect demographics (see Section 9.1.2).  
5. Collect medical history (including alcohol taken), travel history (to SARS-CoV-2 endemic 
countries and SARS-CoV-2 endemic regions of China), and prior/concomitant 
medications/vaccinations (see Section 9.1.2).  
6. Perform “complete” physical examination (see Section 9.1.4).  
7. Check vital signs (see Section 9.1.5).  
8. Perform 12-lead ECG and chest CT test (see Section 9.1.5). 
9. Collect blood sample for eligibility screening tests (hematology, biochemistry, see Section 
9.1.6). 
10. Collect fingertip blood for SARS-CoV-2 and HIV antibody.  
11. Collect oropharyngeal swabs for SARS-CoV-2 testing. 
12. Collect urine sample for eligibility screening urinalysis.  
13. For WOCBP, serum pregnancy testing will be performed at Screening Visit (see Section 9.1.6 
for pregnancy test), and contraception guidance will be provided (see Section 9.1.8 and 9.1.9).  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 74 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
9.3.2 Pre-vaccination procedures 
The following procedures will be performed at Visit 1 (Day 1) and Visit 5 (Day 22):  
1. Collect medical history, travel history (to SARS-CoV-2 endemic countries and SARS-CoV-2 
endemic regions of China), and concomitant medications/vaccinations (see Section 9.1.2).  
2. Perform symptom-directed physical examination (if deemed necessary, see Section 9.1.4).  
3. Assess eligibility criteria (see Sections 7.1 and 7.2) at Visit 1 (Day 1).  
4. Check vital signs (see Section 9.1.5).  
5. Randomize subject (only at Visit 1 on Day 1), a random number was obtained (the random 
number was used as the unique subject ID number) (see Section 9.1.10).  
6. Collect blood sample for clinical laboratory and immunogenicity assessment (see Section 
9.1.6).  
7. For WOCBP, serum pregnancy testing will be performed before boost vaccination (see Section 
9.1.9). 
9.3.3 Vaccination procedures 
The following procedures will be performed at Visit 1 (Day 1) and Visit 5 (Day 22):  
1. Check contraindications to vaccination and criteria for encountering toxicities of vaccination 
(see Sections 7.2 and 7.3).  
2. Prepare the investigational vaccine/placebo according to the Pharmacy Manual (see Section 
8.2)  
3. Inject the investigational vaccine or placebo (see Section 8.2).   
9.3.4 Post-vaccination procedures 
The following post-vaccination procedures will be performed at Visit 1 (Day 1) and Visit 5 (Day 
22):  
1. After vaccination, the subject will be observed for at least 6 hours on site, including 
observation for immediate reactions and body temperature measurement. Vital signs will be 
performed at 1, 3, and 6 h (±15 min) post each immunization. Information should be recorded 
in the eCRF as immediate reactions. The investigator or delegate will take the opportunity to 
remind the subject how to measure solicited reactions and body temperature as part of this 
observation period. All safety data will be collected in the subject’s source documents.  
2. Provide the subject with a diary card, and train the subject on how to use it.  
Careful training of the subject on how to record concomitant medications, how to measure 
solicited reactions and body temperature, how to complete the diary card and how often to 
complete the diary card. Training should be directed at the individual(s) who will perform the 
measurements of solicited reactions and those who will enter the information into the diary 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 75 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
card. This individual may or may not be the subject, but if a person other than the subject enters 
information into the diary card, this person’s identity must be documented in the trial file and 
this person must receive training on the diary card. Training of the subject on how to measure 
a vaccination site AE should be performed while the subject is under observation after 
vaccination.  
Diary card instructions must include the following: the subject must understand that timely 
completion of the diary card on a daily basis is a critical component of trial participation. The 
subject should also be instructed to write clearly and to complete the diary card with sign pen. 
Any corrections to the diary card that are performed by the person completing the diary card 
should include a single strikethrough line with a brief explanation for any change and be 
primeed and dated.  
Please note:  
Diary cards will be the only source document allowed for remote collection of solicited local 
and systemic reactions (including body temperature measurements). The following additional 
rules apply to the documentation of safety information collected by diary card:  
o Diary cards should be reviewed with the subject.  
o No corrections or additions to the diary card will be allowed after it is reviewed with 
the investigator/designee.  
o Any data that are identified as implausible or incorrect, and confirmed by the subject 
to be a recording error should be corrected by the subject on the diary card (the 
correction should include a single strikethrough line and should be primeed and dated 
by the subject).  
o Any blank or illegible fields on the diary card not otherwise corrected as above will be 
missing in the eCRF.  
o The study site should enter all readable entries on the diary card into the eCRF.  
o Any newly described solicited safety information should be added to the diary card by 
the subject and primeed and dated. Any new unsolicited safety information would be 
recorded in the subject source document as a verbally reported event and therefore 
captured as an AE and recorded in the AE eCRF.  
o Starting on the day of vaccine/placebo administration, the subject will check for 
specific types of events at the vaccination site (solicited local reactions), any specific 
generalized symptoms (solicited systemic reactions), body temperature (axillary), any 
other symptoms or change in the subject’s health status, and any medications taken. 
These solicited reactions and body temperature will be recorded in the diary. 
Assessments should preferably take place in the evening at day’s end using the same 
method of measurement every day.  
o Temperature measurement is to be performed using the thermometer provided by the 
study site. If the subject feels unusually hot or cold during the day, the subject should 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 76 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
check his/her temperature. The highest body temperature measured that day should be 
recorded on the diary card.  
o The measurement of solicited local reactions (pain/tenderness, erythema/redness, and 
induration/swelling) is to be performed using the ruler provided by the study site. If 
multiple measurements are taken during the day, the highest measured value should be 
recorded on the diary card.  
o The collection on the diary card of body temperature, solicited local reactions, and 
solicited systemic reactions will continue for a total of 14 days following each 
vaccine/placebo administration. The collection on the diary card of unsolicited AEs 
and medications will continue for 21 days following prime vaccination and 28 days 
following boost vaccination.  
o The healthcare professional reviewing the data on the diary cards will discuss the AEs 
(if any) reported by the subject and will determine if any additional diagnoses and/or 
AEs are present and/or concomitant medications have been used.  
3. At Visit 5 (Day 22), review the previous diary card with the subject and collect it.  
4. Provide contraception guidance (see Section 9.1.8).  
5. Provide the subject with a written reminder of the next planned trial activity. The subject will 
be reminded to complete the diary card daily and to contact the study site if there are any 
questions and to contact the site immediately (or as soon as the subject is medically stable) if 
the subject has a medical condition that leads to a hospitalization or an emergency room visit 
or is otherwise perceived as serious. Available contact details will be provided to the subjects.   
6. Schedule the next site visit with the subjects.  
9.3.5 Main visits post vaccination 
The following main visits post vaccination will be performed:  
1. Collect travel history (to SARS-CoV-2 endemic countries and SARS-CoV-2 endemic regions 
of China) and concomitant medications/vaccinations (see Section 9.1.2).  
2. Perform symptom-directed physical examination (if deemed necessary, see Section 9.1.4).  
3. Check vital signs (see Section 9.1.5).  
4. Collect blood samples for routine safety laboratory testing, immunogenicity assessment and 
CMI testing (see Section 9.1.6).  
5. Collect urine sample for routine safety laboratory testing (urinalysis; see Section 9.1.6).  
6. Review the previous diary card with the subject and collect it (see Section 9.3.4).  
7. Provide the subject with a new diary card, and remind the subject on how to use it (see Section 
9.3.4).  
8. Provide contraception guidance (see Section 9.1.8).  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 77 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
9. Provide the subject with a written reminder of the next planned trial activity. The subject will 
be reminded to complete the diary card daily. The subject will be reminded to contact the site 
if there are any questions and to contact the site immediately (or as soon as the subject is 
medically stable) if the subject has a medical condition that leads to a hospitalization or an 
emergency room visit or is otherwise perceived as serious. All contact details will be provided 
to the subject.  
10. Schedule the next site visit with the subjects.  
9.3.6 Follow-up extension 
The extension visits will be performed at Visit 10 (Month 3), Visit 11 (Month 6), and at Month 12 
(Visit 12). If a subject terminates earlier, a final Visit procedure should be performed, if possible.  
The following procedures will be performed:  
1. Collect travel history (to SARS-CoV-2 endemic countries and SARS-CoV-2 endemic regions 
of China) and concomitant medications/vaccinations (see Section 9.1.2).  
2. Perform symptom-directed physical examination (if deemed necessary, see Section 9.1.4).  
3. Check vital signs (see Section 9.1.5).  
4. Collect blood sample for immunogenicity assessment (see Section 9.1.6.5).  
9.4 Biological sample retention and destruction  
In this trial, specimens for testing will be collected as described in Section 9.1.6. After blood draw 
and serum processing, the serum samples will be preserved and retained as required by applicable 
laws. The Fosun Phar. has put into place a system to protect the subjects’ personal information to 
ensure optimal confidentiality and defined standard processes for sample and data collection, 
storage, analysis, and destruction.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 78 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
10.0 ADVERSE EVENTS  
10.1 Definitions  
10.1.1 Adverse events (AEs)  
Adverse Event (AE): refers to any adverse medical event that occurs in patients or subjects in drug 
clinical study. It does not necessarily have a causal relationship with drug treatment. An adverse 
event can be an unfavorable sign, symptom or disease that is not related to the purpose of the 
medication (including abnormal laboratory tests, etc.), in spite of the causal relationship with the 
drug. 
It includes any new occurrence or deterioration in severity or frequency compared to baseline 
conditions, including abnormal results of laboratory tests (with clinical manifestations). 
AE excludes: 
• 
Medical or surgical procedures, such as operation, endoscopy, tooth extraction, infusion (the 
operation should not be collected as AE, but the diseases leading to these operations should 
be reported as AE); 
• 
Existing diseases or conditions that exist or have been detected but have not worsened prior 
to the start of using the study drug, including abnormal results of laboratory tests. 
• 
Transitory effects on laboratory tests due to the known mechanism of action of the drug, where 
there is no manifest clinical risk or evidence of potential lasting harm, judged by the 
investigator. 
Treatment-emergent AE (TEAE) is defined as any AE with an onset date on or after the first 
administration of IMP (if the AE was absent before the first vaccination of IMP) or worsened after 
the first vaccination of IMP (if the AE was present before the first administration of IMP). AEs 
with an onset date more than 28 d after the last vaccination of IMP will be considered as treatment 
emergent only if assessed as related to IMP by the investigator. 
10.1.2 Solicited reactions  
The occurrence of selected indicators of safety will be measured/collected for 14 days after each 
vaccination (including the days of vaccine vaccination), see details in followingTable 5.  
Table 4  Solicited local and systemic reactions 
Local reactions (vaccination site):  
Pain/tenderness 
Erythema/redness 
Induration/swelling  
Systemic reactions:  
Fever (a)  
Nausea 
Vomiting 
Diarrhea 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 79 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Headache 
Fatigue 
Myalgia 
Arthralgia 
Chills 
Loss of appetite 
Malaise 
(a) Based on recorded body temperature, fever is defined as axillary temperature ≥37.3°C.  
The intensity of solicited safety parameters will be assessed respectively as described in grading 
scale of Appendix B and C. 
Solicitation adverse reactions: there is at least a reasonable possibility of a causal relationship 
between vaccines and adverse events, that is, causality cannot be ruled out. 
10.1.3 Serious adverse events (SAEs)  
Serious Adverse Event (SAE): Serious adverse event is defined as any untoward medical 
occurrence that (at any dose): 
 
Results in death 
 
Is life-threatening 
(It refers to an event in which the patient is at risk of death at the time of the event; it does not refer 
to an event which hypothetically may have caused death if it is more severe.) 
 
Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization is defined that the patient stays in the hospital or emergency ward 
for observation (usually stays for one night at least) and/or receives the treatment which is not 
suitable to be given in doctor’s office or outpatient department. Complications that occur during 
hospitalization are also considered as AE. If a complication prolongs hospitalization or meets any 
other criteria of serious event, the event is serious. When it is uncertain whether it is hospitalization 
or whether hospitalization is needed, the event should also be considered serious. Hospitalization 
required by selective treatment or due to original disease which does not get worse since baseline 
does not belong to AE. 
 
Results in persistent or significant disability/incapacity 
Note: Disability is defined that the person’s ability to do activity of normal life is significantly 
influenced. It does not include events with little clinical significance, such as simple headache, 
nausea, vomiting, diarrhea, flu or accidental trauma (such as ankle sprain). These events may 
influence daily life function, but they will not result in obvious loss of function. 
 
Caused a congenital anomaly/birth defect of offspring 
 
Other significant medical events 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 80 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Other significant medical events: In some cases, medical and scientific judgment should be made 
to decide whether expedited report is needed. If the significant events do not immediately threaten 
life, cause death or require hospitalization, but medical measures are needed to prevent the above 
situation, then these event are also considered serious. 
Note: The following hospitalization treatments are not considered as serious adverse events, since 
there are no adverse events related to hospitalization (i.e, there are no adverse medical events).  
 
Temporary care and hospitalization 
 
Hospitalization due to social reason, for example, hospital admission for convenient care. 
 
Scheduled hospitalization according to the study protocol, for example, hospitalization 
for administration of the study vacccine or insertion of study vacccine or laboratory test 
required by protocol. 
 
Scheduled hospitalization, selective operation or examination which the patient plans to 
undertake for pre-existing disease prior to the informed consent (in this case, the disease 
that requires hospitalization does not get worse or develop into a new disease after the 
administration of study vacccine, which should be also proved by the original document). 
 
Hospitalization for daily maintenance of equipment which have been in place before study 
(such as battery replacement). 
Any confirmed cases of COVID-19 disease that occur during observation should be reported as 
SAE, where the intensity of the corresponding AE is rated as "moderate" or "severe" (according to 
the criteria provided in appendix B and appendix C), and necessary isolation or hospitalization 
should be performed in accordance with the Diagnosis and Treatment Protocol for Novel 
Coronavirus Pneumonia (Trial Version 7). If no other SAE definition is deemed appropriate, then 
"other significant medical events" should be used as the SAE criterion.SAE forms should be 
completed, including follow-up information, as detailed in section 10.2.3, for the preparation and 
distribution of SAE reports and notes. 
10.1.4 Adverse events of special interest 
Enhanced respiratory disease or flu-like symptomatology not-resolved after 7 d or with symptom 
kinetics that are inconsistent with a relationship to RNA immunization, judged by the investigtors, 
will be considered adverse events of special interest (AESI). 
All AESI, whether or not serious adverse events, whether or not have causal relationship with the 
investigational product, need to inform Beijing Fosun medicine science and technology 
development co., LTD. (the Fosun) within 24 hours, and fill out the form of serious adverse events 
and send to the pharmacovigilance department. If the adverse events of special interest meet the 
SAE standard, it needs to be handled and reported according to the SAE. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 81 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
10.1.5 AE associated with an overdose or error in vacccine administration 
If the subject presents with symptoms due to overdose or error in vacccine administration, the 
vacccine administration of overdose and error and all related symptoms should be recorded on AE 
page of eCRF and should be reported to the Fosun according to the SAE procedure. The overdose 
which does not cause any symptoms should also be immediately reported within 24 hours. If there 
are serious consequences or the subject presents with symptoms which meet the assessment criteria 
of SAE after overdose, this overdose should be reported as SAE. 
10.2 Collection and record of safety events  
10.2.1 Collection and reporting of solicited reactions  
The occurrence of selected symptoms indicative of safety will be collected on diary cards by 
the subjects for 14 days following each investigational vaccine/placebo administration (i.e, the day 
of vaccination +13 subsequent days) and will be recorded on the “Local and Systemic reactions” 
eCRF (if applicable). These will be summarized in the final report under the category “solicited 
reactions” to differentiate them from unsolicited AE. Any solicited local or systemic reaction 
observed beyond 14 days after vaccination will be recorded as unsolicited AE on the Adverse Event 
eCRF. Any solicited continuing local (vaccination site) or systemic reactions observed beyond 14 
days following each trial vaccination will be additionally recorded on the Adverse Event eCRF for 
follow-up. For these persistent/prolonged solicited reactions, the end date will be captured on the 
Adverse Event eCRF to permit a separate analysis from the unsolicited AE. 
10.2.2 Collection and reporting of unsolicited AEs  
Unsolicited AE occurring within 21 days after the prime vaccination and within 28 days after boost 
vaccination of vaccine/placebo will be collected on diary card (ie, day 22 to day 50 of the trial). 
AEs leading to withdrawal or discontinuation will be collected throughout the trial. Investigators 
should report collections of signs and symptoms as diagnosis AEs e.g. ‘flu-like symptoms’ or 
‘injection site reaction’. 
Related AE/SAE occurring after 28 days after boost vaccination should also be collected and 
reported. 
The following information will be documented for each event:  
• 
Reported term for the Adverse Event,  
• 
Start and end date,  
• 
Serious (Y/N),  
• 
Severity should be judged clincially by the investigator according to the grading standard in 
10.3.1. For reference to the specific events listed in Appendix B and Appendix C, refer to the 
grading standards of the corresponding guidelines. 
• 
Investigator’s opinion on the causality (relationship) between the event and administration of 
trial vaccine(s),  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 82 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
• 
Investigator’s opinion of the causality (relationship) to trial procedure(s), including the details 
of the suspected procedure,  
• 
Actions taken,  
• 
Outcome of event.  
10.2.3 Collection and reporting of SAEs  
For any SAE during the trial, the investigator should actively take appropriate action to ensure the 
safety of subject, no matter whether the SAE is related to study vacccine. The investigator should 
report to Fosun whthin 24 hours of being informed of the SAE.  
For reports of deaths, the investigator shall provide the Fosun and the ethics committee with other 
information as required, such as an autopsy report and a final medical report. 
The investigator shall sign and read the clinical trial safety information provided by the sponsor in 
a timely manner, and shall consider the treatment of the subject, whether to adjust accordingly, 
communicate with the subject as soon as necessary, and report to the ethics committee the 
suspicious and unexpected serious adverse reactions (SUSAR) provided by the sponsor. 
The investigator shall follow up the SAE according to the protocol requirements, and provide a 
detailed, written follow-up report within 24 hours after receiving the follow-up information, in the 
same manner as above. 
The sponsor or its representative shall evaluate and report the SAE (including SUSAR) in the 
clinical trial in accordance with the latest applicable regulatory requirements for the clinical trial 
of the investigational product. 
Contacts of serious adverse event reports: 
Table 5 Contact information for serious adverse events reporting 
Unit 
Phone 
Reporting way 
Pharmacovigilance Department of 
Beijing Fosun 
 
Email: FSADEDESK@fosunpharma.com 
Jiangsu Center for Disease Control 
and Prevention 
 
 
10.3 Assessment of safety parameters 
10.3.1 Assessment of intensity 
Reaction signs and symptoms involved in the grading scale will be graded respectively by the 
investigator according to the Guidelines for Adverse Event Classification Standards for Clinical 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 83 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Trials of Preventive Vaccines of NMPA (Appendix B) and FDA (Appendix C). AEs uninvolved in 
the grading scale will be graded clinically by the investigator according to following criteria. 
Grading and seriousness need to be assessed independently for each AE recorded on the CRF. 
Mild  
Grade 1  
Lasting for a short time (<48h) or slight discomfort, which do not 
influence activity and no treatment is needed. 
Moderate  
Grade 2  
Mild or moderate limitation of activity, which may require hospital 
visit, does not require or only requires mild treatment. 
Severe  
Grade 3  
Obvious limitation of activity, which requires hospital visit and 
treatment, possibly requires hospitalization. 
Critical 
Grade 4 
Possibly life-threatening; serious limitation of activity, which 
requires intensive care 
Death 
Grade 5 
 
10.3.2 Relationship to investigational drug 
Relatedness (causality) to vaccine will also be assessed by the investigator. The relationship 
between each AE, including solicited systemic AEs (solicited local AEs are considered as related) 
to trial vaccine(s) will be assessed using the following categories:  
• 
Definitely related: There is reasonable time relationship between drug administration and the 
occurrence of adverse event; after drug withdrawal, the adverse reaction disappears or is 
rapidly relieved and improved (ie, dechallenge positive); when the drug is administrated again, 
the adverse event appears again (ie, rechallenge positive) and may get worse obviously; 
meanwhile, there is evidence from investigator brochure or literature data; besides, influence 
from original disease and other confounding factors are excluded. 
• 
Probably related: There is no history of repeated drug administration. The rest are the same as 
those for “definitely related”, or even if there is drug combination, the possibility of adverse 
reaction resulted from drug combination is generally excluded. 
• 
Possibly related: There is close relationship between drug administration and adverse event, 
which can also be proved by literature data. However, there may be more than one drug which 
causes adverse event or the original disease progression cannot be excluded. 
• 
Possibly unrelated: The relationship between adverse event and medication time is not close. 
The clinical manifestation is not consistent with the known adverse events of the drug. If the 
original disease develops, it may have the similar clinical manifestation. 
• 
Unrelated: No drug is administrated, or there is no association between drug administration 
and the occurrence time of adverse event or there is other definite reason which results in 
adverse event.  
Related, probably related and possibly related are listed as related to the investigational vaccine.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 84 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
10.3.3 Relationship to trial procedures  
Relationship (causality) to trial procedures should be determined for all AEs.  
The relationship should be assessed as “Yes” if the investigator considers that there is reasonable 
possibility that an event is due to a trial procedure. Otherwise, the relationship should be assessed 
as “No”.  
10.3.4 Expectation assessment of adverse events 
An unexpected adverse reaction refers to an adverse reaction with the nature, severity, consequence, 
or frequency different from the expected risks described in the current relevant data of the 
investigational vacccine (such as investigator brochure or another document). Investigator 
brochure is used as the main document to provide safety reference information to judge whether 
an adverse reaction is expected or unexpected. 
Suspected unexpected serious adverse reaction (SUSAR): refers to a suspected and unintended 
serious adverse reaction with the nature and severity of clinical manifestations beyond the existing 
data and information in investigator brochure of investigational vacccine, package inserts of drugs 
on market or summary of product characteristics, etc. 
10.4 Follow-up of adverse events 
The investigator should follow up each adverse event. The laboratory test of clinical indicators 
shall be retested in time if there are ≥ Grade 1 or clinically significant abnormal items judged by 
the investigator. For all SAEs and AEs with relevance which still exist until the end of AE/SAE 
collection and record, the investigator should follow up to: 
• 
The event is solved or resumes to the status of baseline or is stable; 
• 
The investigator can confirm that there will be no further improvement; 
• 
No more information can be obtained (the subject refuses to provide more information, or 
there is evidence which proves that the subject is lost to follow-up even if the investigator 
has tried his/her best). 
During the study, the recovery time (with date) of adverse event should be recorded in AE eCRF 
and the patient’s medical record to verify the original data. 
For serious adverse events, adverse events of special interest and pregnancy events, the Fosun or 
other designated personnel can obtain more case information through telephone, fax, e-mail and/or 
supervising to perform independent medical assessment for these cases. 
The AE original data records updated after the lock of database are available for backup. SAE 
information needs to be filled in the Serious Adverse Event Report Form as detailed as possible, 
which is reported to PV department. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 85 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
10.5 Treatment of reactions and adverse events  
Treatment of any reaction or AE is at the sole discretion of the Investigator and according to local 
standard of care. 
Mitigation plans for specific reactions 
Based on experience with other BioNTech RNA-based vaccines, it is anticipated that subjects may 
experience TEAEs of flu-like symptomatology and/or injection site reactions following the 
administration of RNA vaccines due to the mechanism of action of RNA-vaccines. This may 
include fever, chills, rigors, tachycardia, arthralgia, myalgia, headache, nausea. Treatment of these 
events is dependent on the discretion of the investigators; however, the following management 
suggestions are provided: 
• 
Treat fever with acetaminophen or nonsteroidal anti-inflammatory drug (NSAIDs) with a dose 
recommended by the investigational site. 
• 
After the first occurrence of flu-like symptomatology, subjects can be treated with standard 
therapeutic dose of acetaminophen, or NSAIDs, starting at least 2 h after the immunization. 
• 
Corticosteroids should be avoided as either prophylaxis or treatment as it counteracts the 
effects of immunization. 
• 
Local injection site reactions can be treated with simple measures such as cooling, antipyretics, 
analgesics.  
Ensure adequate hydration of trial subjects on the day of immunization. Consider administering 
fluids (e.g., water for drinking, 0.5 - 1.0 L) within approximately 2 h following the immunization 
according to the standard of investigational site. 
If subjects experience enhanced respiratory disease or progression of flu-like symptomatology, 
such as non-resolution of the symptoms after 7 d, symptom changes that are inconsistent with a 
relationship to RNA immunization, additional diagnostic measures should be considered and the 
medical supervisor should be informed. 
10.6 Outcome of adverse events  
The investigator should determine the outcome of adverse events according to its prognosis. The 
outcome of adverse events is as follows:  
• 
Recovered/resolved: The subject is fully recovered from AE, without any residual influence 
or damage. 
• 
Recovering/resolving: The signs and symptoms related to the event are relieved but have not 
disappeared completely. 
• 
Recovered/resolved with sequelae: The subject is recovered, still with residual influence or 
damage. The residual influence may be temporary, but still exists at the time of report. If 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 86 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
these sequelae are not considered permanent, new information should be provided at follow-
up when there is change of the event. 
• 
Unchanged: The signs and symptoms related to the event are not relieved. The condition of 
the subject remains unchanged. 
• 
Aggravated: The signs and symptoms related to the event are not relieved. The condition of 
the subject is aggravated. 
• 
Fatal: Only when the death is resulted from SAEs, the fatal can be chosen as an outcome. All 
other AEs/SAEs which exist at death should be reported. 
• 
Unknown: It refers to a situation when the subject is lost to follow-up and the investigator 
cannot confirm the outcome.

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 87 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
11.0 Monitoring Committee 
11.1 Safety Review Committee (SRC) 
Safety Review Committee (SRC) will be established comprising investigators, Fosun medical 
representatives, and medical monitor, etc. 
Key roles of the SRC are as follows: 
• 
Before progression to the next age group (elderly group), assess the safety and 
tolerability data of the subjects in the adult group completed safety visits up to 14 days 
after prime vaccination, and decide whether to approve initiation of the dose cohort of 
elderly group. Data collected include vital signs, TEAEs, local reactions, blood/clinical 
laboratory data, and brief physical examination outcome.  
• 
Before each dose cohort begins boost vaccination, for each dose cohort, assess the safety 
and tolerability data of the prime vaccination of subjects (including data collected at least 
up to 14 days post-vaccination) and, decide whether to approve initiation of boost 
vaccination of this dose cohort. Data collected include vital signs, TEAEs, local 
reactions, blood/clinical laboratory data, and brief physical examination outcome. 
• 
Throughout the trial, assess whether to replace trial subjects permanently discontinued 
due to safety issues. 
• 
Throughout the trial, the SRC may specific additional dose levels to be tested and an 
appropriate regime for enrollment and safety oversight. 
See SRC charter for more information. The SRC will act according to written procedures described 
in SRC charter.  
11.2 Independent Data Monitoring Committee (IDMC)  
The study will be overseen by an Independent Data Monitoring Committee (IDMC). IDMC will 
consist of 3 or 5 independent members (including epidemiologist, clinical experts, and statistical 
expert) and 1 independent non-voting statistician. 
The IDMC is required to review the unblinded data when a significant event or risk that could 
cause the study to be suspended occurs. Based on the results of the safety data review, IDMC can 
request the suspension of investigation in a certain dose group/age group, or suspension of boost 
vaccination, and can also provide recommendations for subsequent development based on the 
periodical study data. This study will proceed in accordance with the protocol-specified procedures 
if no IDMC recommendation for suspension or modification is received.  
The IDMC meetings will consist of open and closed face-to-face meetings or teleconference calls. 
The type and frequency of scheduled meetings will depend on the subject enrollment and safety 
event rates. Unscheduled ad hoc meetings will occur if a stopping rule occurs, or at any time 
consultation is requested by the Pharmacovigilance Study Team.   

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 88 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
The IDMC will review safety data on an ongoing basis, except at regular review time points. When 
the reported AEs meet with the dose-limiting toxicity (DLT) criteria, the IDMC will review all 
relevant safety data and consider a possible pause of the study, if it deems necessary:  
See IDMC charter for more information. The IDMC will act according to written procedures 
described in IDMC charter.   

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 89 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
12.0 DATA MANAGEMENT  
Data management ofthis project is implemented based on the requirement from Technical 
Guideline for Data Management of Clinical Trial, Guiding Principle for Planning and Reporting 
of Data Management and Statistical Analysis for Drug Clinical Trial, Technical Guiding Principle 
for Electronic Data Collection of Clinical trial, issued in 2016 by NMPA. 
12.1 Data collection and management  
Data collection and management is conducted with the electronic data collection (EDC) system in 
this study. The data of subjects will be recorded in the designated eCRF. The eCRF will be 
preserved by the Fosun and its copy will be sent to the investigator as a research copy. 
The investigator or authorized staff is responsible to fill out the eCRF. They should carefully record 
the items of eCRF in detail. Blank or missing of an item is not permitted (for the blank without 
record, UK/NA/ND should be filled in according to the fact); all data in eCRF should be verified 
with the data of original material to guarantee the accuracy. 
The investigator must preserve all original laboratory test reports or the copies; in terms of 
abnormal laboratory or examination data, the investigator should verify these data and explain 
whether they have clinical significance or not; the investigator should fill in eCRFs strictly 
following the eCRF instructions. 
12.2 Database lock 
When the following conditions are met, data can be locked. 
• 
All data are entered into the database. 
• 
All issues are solved. 
• 
Statistical analysis set has been confirmed and judgment is made. 
The locked data and document cannot be changed without the Fosun’s authorization. 
The detailed process of data management will be described in DMP. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 90 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
13.0 STATISTICAL METHODS  
13.1 Statistical and analytical plans  
The statistical analysis plan (SAP) will be finalized prior to unblinding of subject’s treatment 
assignment. SAP will provide further details regarding the definition of analysis variables and 
analysis methodology to address all trial objectives.  
A review of data under blind state will be conducted prior to unblinding of subject’s vaccination 
assignment. This review will assess the accuracy and completeness of the trial database, subject 
evaluability, and appropriateness of the planned statistical methods.  
13.1.1 Analysis sets  
• 
Safety Set: Safety Set will consist of all randomized subjects who receive at least one dose of 
the investigational vaccine/placebo and at least one safety evaluation.   
• 
Total Vaccinated Cohort (TVC): According to intention-to-treat analysis set principle, the TCV will 
include all randomized subjects who have received at least one dose of the investigational 
vaccine/placebo and can provide with effective baseline.  
• 
Per protocol set (PPS): The PPS will include all subjects in the TVC who have no major 
protocol violations and complete boost vaccination. The protocol violation criteria will be 
defined as part of the blinded data review. The categories of major protocol violations include:   
1 
not meeting inclusion criteria, or meeting exclusion criteria,   
2 
receiving a wrong investigational vaccine/placebo,   
3 
receiving prohibited therapies,  
4 
other major protocol violations that be identified during blinded data reviews.  
All summaries and analyses of safety data will be based on subjects in the Safety Set.   
The primary immunogenicity endpoint analyses will be based on the PPS and TVC, and secondary 
immunogenicity endpoint analyses will be based on the TVC.  
13.1.2 General principles 
Data is usually summarized by groups, and groups can be merged as appropriate. 
The following descriptive statistics will be used: number of subjects (n), mean, standard deviation, 
median, minimum, and maximum will summarize the continuous variables by groups. 
The categorical variables are summarized by groups, listing the absolute value and relative 
frequency (n and %) of the subjects in each category. 
Baseline was defined as the last available value before the first administration. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 91 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
13.1.3 Analysis of demographics and other baseline characteristics  
Summaries of age, gender, race, and other baseline characteristics will be presented by groups of 
BNT162b1 and placebo.  
13.1.4 Primary endpoints 
All AEs will be coded using the most recent version of Medical Dictionary for Regulatory 
Activities (MedDRA version 23.0) coding system to get a system organ class (SOC) and preferred 
term (PT) for each AE. 
AEs and solicited reactions will be summarized using the Safety Set. In general, safety parameters 
will be analyzed by grouping and for each immunization, i.e., for: 
• Day 1-21 (pre-boost) 
• Day 21(post-boost) - 28 
Additionally, AEs and reactions will be summarized for all dose levels combined for each type. 
For each analysis, the number and percentage of subjects reporting at least one AE will be 
summarized by PT nested within SOC for each of the following AE types using the Safety Set: 
• Any AE 
• Related AE 
• ≥Grade 3 AE 
• Related AE ≥Grade 3  
• AE leading to withdrawal 
• Any SAE 
• Related SAE 
Moreover, the number and percentage of subjects with any AE will be summarized by worst grade 
by PT nested within SOC. 
During 14 days post vaccination (including the day of BNT162b1/placebo vaccination), evaluate 
reactogenicity by daily solicited reactions, including local reactions (vaccination site: 
pain/tenderness, erythema/redness, induration/swelling) and systemic reactions (nausea, vomiting, 
diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever), as well 
as non solicited AE. In addition, body temperature (axillary) was collected as the indicator of 
reactogenicity (fever was defined as axillary temperature ≥37.3℃ or oral temperature ≥38℃). 
For each solicited reaction (including fever), the percentage of subjects will be aggregated 
according to the severity of the events and the total number of subjects within 14 days of each 
vaccination/placebo. 
Local and systemic responses were recruited within 14 days after each vaccination, non-solicited 
TEAE within 21 days after the prime vaccination and 28 days after boost vaccination, and IMP-

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 92 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
related AE were studied after 28 days. Adverse reaction classification criteria given in appendix B 
and appendix C were used for classification. During the study period, AEs uninvolved in the 
appendix grading scales will be graded clinically by the investigator according to the criteria in 
Section 10.3.1. 
For each immunization, the number and percentage of subjects reporting at least one local reaction 
or systemic reaction will be summarized for each of the following types using the Safety Set: 
• Any local reactions or systemic reactions 
• Related local reactions or systemic reactions 
• Grade ≥3 local reactions or systemic reactions 
• Related grade ≥3 local reactions or systemic reactions 
Moreover, the number and percentage of subjects reporting at least one local reaction will be 
summarized by worst grade using the Safety Set. 
13.1.5 Immunogenicity analysis  
Descriptive statistics for the primary and secondary immunogenicity endpoints, including 
estimates and 95% confidence intervals (95% CI) for GMT and SCR, will be provided by time 
point and by different age groups, different dose cohort of BNT162b1 and placebo group). 
Different BNT162b1 dose cohorts will be compared in pairs, and the GMT ratio of each two dose 
cohorts as well as the point estimate value of SCR difference and 95% CI will be calculated. 
Generally, immunogenicity will be summarized and analyzed based on age groups and dose 
cohorts. 
• 
Seronegative subjects: Subjects with no detectable serum antibodies (test results are lower than 
the lower limit of detection) as measured by ELISA/neutralization assay.   
• 
Seroconverted subjects: The serum antibody titer after vaccination of subject is at least 4 times 
higher than baseline by ELISA/neutralization assay. 
13.1.6 Safety analysis  
Clinical laboratory parameters 
Clinical laboratory parameters at each timepoint and change from baseline to each post-baseline 
time point will be summarized using descriptive summary statistics for each parameter by group. 
Shift tables from baseline to worst intensity grade will be provided for each laboratory parameter 
by group. Make a list and descriptive summary from normal baseline to post-vaccination 
abnormality, or from abnormal baseline to post-vaccination enhancement of severity. 
Additionally, the occurrence of clinically significant abnormal laboratory results within a trial 
subject will be analyzed using descriptive summary statistics for each parameter and visit by group. 
Laboratory parameter results will be listed along with the normal ranges. Values that are below or 
above the normal ranges will be flagged. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 93 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Vital signs 
Vital sign parameters at each time point and change from baseline to each post-baseline time point 
will be summarized using descriptive summary statistics for each parameter by group. 
ECG 
ECGs will be judged by the investigator as clinically significant (yes/no). The number and 
percentage of trial subjects with clinically significant ECG findings will be summarized by group 
for each visit. 
A safety summary will be given by age groups and dose cohorts/placebo group. 
13.2 Periodical Analysis   
Initial analysis: all available safety and immunogenicity data will be included when all subjects in 
each age group complete Visit 9 (Day 50, 28 days after boost vaccination) to perform initial 
analysis. All available safety and immunogenicity data will be included when all subjects in each 
age group complete Visit 11 (visit at Month 6 after prime vaccination), Visit 12 (visit at Month 12 
after prime vaccination), will update the statistical analysis.  
Unblinding will be occurred after the completion of the initial analysis of immunogenicity and 
safety observation 28 days after boost vaccination, but the subjects will be kept blinded. More 
details regarding the analyses will be provided in the Statistical Analysis Plan (SAP).  
The phase analysis report will be prepared after each time of analysis and the overall study report 
will be prepared at the end of study.   
13.3 Determination of sample size  
This study is a phase Ⅰ exploratory clinical trial.  
In the study, approximately 24 subjects will be included in each BNT162b1 dose cohort of each 
age group, with another 24 subjects vaccinated with placebo. If the occurrence of TEAE is 8%, 
the probability of observation of at least one TEAE in 24 subjects in each dose group is 86.5%, 
which is sufficient to perform safety evaluation for investigational vaccine at each dose level.

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 94 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
14.0 STUDY MANAGEMENT  
14.1 Ethical considerations 
This study will be conducted in accordance with the ethical requirements of the Declaration of 
Helsinki (Fortaleza 2013 edition), the International Conference on Harmonization (ICH) E6 Good 
Clinical Practice, national laws and regulations related to clinical study, and this study protocol. 
The study protocol, informed consents, case report forms and other materials must be submitted to 
the ethics committee for approval before the study begins. The ethics committee will strictly follow 
the requirements of relevant laws and regulations to review and approve these materials. Only after 
receiving the approval of the ethics committee can the study be started. 
During the study process, any changes to the protocol must be reviewed and approved by the ethics 
committee before they can be implemented. 
In addition, the ethics committee will approve all clinical trial protocol amendments (except for 
Fosun approved administrative changes), informed consents and updates, subject recruitment 
procedures, written information to be provided to the subjects, available safety information, 
information about payment and compensation available to subjects, the Investigator’s curriculum 
vitae and/or other evidence of qualifications, and any other documents requested by the ethics 
committee and regulatory authority as applicable. 
14.2 Informed consent 
The investigator or his/her designated representative will be responsible for explaining the study 
background, the pharmacological characteristics of the investigational medicinal product, the 
study protocol, and the benefits and risks of participating in the study to each subject, the legal 
representative of the subject or independent witness, and must give the subjects enough time and 
opportunity to ask about the details of the trial, allow them to obtain satisfactory answers for their 
questions and decide whether to participate in the study. Before a subject enter the study (before 
the screening test), the written informed consent signed by the subject or his/her legal 
representative and the investigator or his/her representative physician should be obtained. 
The final text of the informed consent should include the following: study background, study 
objectives, study process, matters about subject cooperation, risk and discomfort of study 
participation, possible damage caused by trial-related operations, storage and handling of 
biological samples, benefits of study participation, alternative treatment, and related costs of study 
participation; treatment and appropriate insurance compensation a subject will receive in the event 
of damage related to the study; access to the study data and the confidentiality of subject 
information, etc. This informed consent should be written in non-technical language and approved 
by the institutional review board/independent ethics committee. 
The subject or his/her legal representative, investigator who performs the informed consent process, 
or his/her representative is required to sign and date the informed consent. The informed consent 
should be kept by the investigator and the subject. If important new data related to the 
investigational drug or new information that will affect the subject’s willingness to continue 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 95 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
participating in the study is found, the subject or his/her legal representative shall be notified in 
time to obtain the subject’s informed consent again. 
14.3 Protocol amendments 
Any important modification to this protocol requires written amendments approved by the sponsor 
and Fosun and the investigator before implementation and reported to the ethics committee for 
approval and sent to the regulatory agency for filing. 
Any changes to the protocol require written protocol amendments, and administrative changes 
must be approved by the sponsor and Fosun before implementation. If the change has a special 
impact on the safety of subjects, the scope of the study or the scientific quality of the study, an 
application needs to be submitted to the regulatory agency and the approval of the appropriate 
ethics committee of each study institution should be obtained. The above requirements shall not 
prevent the investigator or Fosun from taking immediate actions to protect the safety interests of 
all subjects. If the investigator believes that, for safety reasons, the protocol needs to be changed 
or deviated immediately to eliminate the harm to subjects, the medical monitor and the ethics 
committee of the study site should be notified immediately. The Fosun must notify the regulatory 
agency in accordance with local regulations. 
For protocol amendments that only involve study management or administrative aspects, there is 
no need to apply to the regulatory agency or ethics committee, but the regulatory agency or ethics 
committee should be notified in accordance with local regulations. 
14.4 Protocol deviations 
If no formal clinical trial protocol amendment is determined and approved by the appropriate ethics 
committee, the investigator must not deviate from the study protocol unless it is to eliminate direct 
harm to the subject or when the change only involves the management or administrative aspects 
of the study and is approved by the medical monitor and/or the Fosun. 
All requirements specified in the study protocol must be strictly implemented. Any intentional or 
unintentional deviation or violation of the trial protocol and GCP principles can be classified as 
deviation from the protocol or violation of the protocol. The investigator or personnel designated 
by the investigator should record and explain the details and reasons of the deviation/violation of 
the protocol, and inform the regulatory agency or ethics committee according to local regulations. 
For the specific protocol deviation or protocol violation, see the medical monitoring plan. 
14.5 Subject confidentiality and privacy 
The subjects' personal information and privacy will be kept strictly confidential. During the study 
period, the subject's name and other personal data will be replaced by code or number. The 
collection and processing of personal data from subjects enrolled in this study will be limited to 
data that are essential to investigate the efficacy, safety, tolerability, quality and utility of the 
investigational drug. These data must be collected and processed with adequate precautions to 
ensure confidentiality and compliance with applicable data privacy protection laws and regulations. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 96 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
The monitor, other authorized representatives of the Fosun, ethics committee, and representatives 
of the regulatory agency can consult these subject records. The results of the study may be 
published in a journal, but no personal information of subjects will be disclosed. 
14.6 Monitoring 
The investigator should allow the clinical research associate to inspect outpatient, laboratory, and 
pharmacy facilities, and review case report forms, informed consents, and all original data, thereby 
ensuring that the study complies with the Good Clinical Practice and local regulations. 
According to the monitoring plan, the designated clinical research associate will conduct 
monitoring visits to each study site. Before the study begins, a site visit will be conducted. During 
the study, regular visits are required. Contact by telephone, fax or email can be used as needed as 
a supplement to the site visits. 
Before the start of this study, the investigator will be notified of the expected frequency of 
monitoring visits. In addition, during the study, the investigator will be notified in advance before 
each monitoring visit. The purpose of visits is to ensure that the implementation of clinical study 
strictly adheres to the study protocol; and ensure the completeness and accuracy of the case report 
forms, which can be confirmed from the original documents. 
The clinical research associate verifies that all case report forms are correctly and completely filled 
out and are consistent with the original data; all errors or omissions have been corrected or noted, 
signed and dated by the investigator. At each visit, in order to review and verify the case report 
forms, drug supply and inventory records, drug release and recovery records, and any additional 
records arranged, close cooperation between the investigator and clinical research associate is 
needed. 
14.7 Quality assurance and quality control 
The Fosun, investigator and contract research organization should perform their respective duties 
in accordance with the requirements of the GCP, strictly follow the trial protocol, and adopt the 
corresponding standard operating procedures to ensure the implementation of quality control and 
quality assurance systems for clinical tests, sample testing, data statistical calculations and other 
processes. 
To ensure the quality of the study, all investigators must be trained for the trial protocol before the 
start of the trial. The SOPs must be strictly implemented during trial. The Fosun should send 
qualified monitors to supervise the trial process and verify the trial data. 
The Fosun can entrust an inspector to conduct a systematic inspection of the trial-related activities 
and documents to verify whether the trial is conducted in accordance with the trial protocol, 
standard operating procedures, and relevant regulations and technical guidelines, and whether the 
trial data is recorded and reported in a timely, true, accurate and complete manner. Inspection 
should be performed by personnel independent of the clinical trial. 
Relevant materials and documents (including case records) of study sites and laboratories 
participating in the clinical trial should be inspected and verified by the drug regulatory authority. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 97 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
14.8 Direct access 
The principal investigator will provide direct access to the source data and documents to the ethics 
committee personnel, monitors, and other designated personnel of the Fosun who conduct the 
study-related monitoring and/or review. The purpose of the monitoring or inspection is to 
systematically and independently review all study-related activities and documents, and determine 
whether these activities have been carried out, and record, analyze, and accurately report data 
according to the protocol, GCP, ICH guidelines, and any appropriate regulatory requirements. If 
the regulatory agency contacts the study site and/or the principal investigator for verification, the 
principal investigator will immediately notify the Fosun. 
The investigator must inform the subject that his/her study-related records can be reviewed by the 
above individuals without infringing on the privacy of the subject’s personal health information. 
14.9 Data recording and storage  
To ensure the evaluation and supervision of the regulatory agency and the Fosun, the investigator 
should agree to keep all study data, including confirmation records for all subjects (all recorded 
data, such as case report forms and hospital original records, can be effectively checked), all 
original signed subject informed consents, all case report forms, detailed records of drug 
distribution, etc. The storage period is 5 years after the end of the study or until the time limit 
agreed in the clinical contract and until the notification of destruction by the Fosun is obtained. 
All the materials of this clinical study belong to the Fosun. Investigator shall not provide them to 
third parties in any form without the Fosun’s written consent unless required by the regulatory 
agency. 
14.10 Subject insurance and indemnity 
The sponsor will provide insurance to every subject participating in the study in accordance with 
all applicable laws and regulations. 
If a subject does suffer from an injury that has a causal relationship with the study due to 
participation in the study, the Fosun will bear the cost of treatment and corresponding economic 
compensation, except for those caused by medical accidents. 
14.11 Storage and use of biological specimens  
The biological samples of this study will be stored at the designated location for the use of this 
clinical study only. The blood samples will be destroyed after the test is completed, and the backup 
blood samples will be kept according to the requirements of national laws and regulations until a 
specified time after the investigational drug is approved for marketing. 
14.12 Study interruption and early termination 
The sponsor and Fosun reserve the right to stop the study at any time due to medical reasons or 
any other reasons. If the study is terminated or interrupted early, the Fosun should immediately 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 98 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
notify the investigator that the study has been terminated or interrupted, and explain the reason for 
the termination or interruption of the study. In accordance with the requirements of relevant 
regulations, the Fosun or investigator should also immediately notify the ethics committee that the 
study has been terminated or interrupted, and explain the reason. 
The investigator reserves the right to decide whether the study should be stopped or not. If the 
investigator terminates or interrupts the study without the prior consent of the Fosun, the 
investigator should immediately notify the Fosun and the ethics committee and provide the Fosun 
and the ethics committee with detailed written explanations regarding the termination or 
interruption of the study. Study records must be kept. 
14.13 Study summary report 
After the end of the study, the investigator and the Fosun should objectively summarize the study 
results, statistically analyze the study data using appropriate statistical methods, make an objective 
evaluation of the drug safety based on the results, and prepare a written summary report of this 
clinical study after review and approval by the sponsor and Fosun. 
14.14 Information disclosure and data publishing policy 
The investigator should keep the information and data related to this study confidential and do not 
cite or publish relevant study results or data without the sponsor and Fosun’s consent. 
The sponsor and Fosun have the right to publish information or data related to this study, or report 
it to the regulatory authority. If the sponsor and Fosun need to display the name of the investigator 
in the publication or advertising content, it should obtain the investigator's consent. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 99 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Appendix A WHO and CDC Website  
• 
World Map indicating Areas with Risk of COVID-19: 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019 
• 
COVID-19 Map of China: http://2019ncov.chinacdc.cn/2019-nCoV/ 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 100 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Appendix B NMPA Guidance for Adverse Events Grading Scale for Preventive Vaccine 
Clinical Trials in China   
Appendix B Table 1 Grading scale for vaccination site (local) adverse events  
Symptoms/signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Pain and tenderness (optional; use tenderness for subjects who cannot express pain autonomously) 
Pain 
Do not affect or 
slightly affect 
physical activity 
Affect physical 
activity 
Affect daily life 
Loss of basic self-care 
ability, or hospitalization 
Tenderness 
Resist or flinch 
after touching 
Cry after touching, 
but can be soothed 
Cry continuously, 
unable to be 
soothed 
Need emergency treatment 
or hospitalization 
Induration*, 
swelling** #  
2.5 ~ <5 cm in 
diameter or 6.25 
~ <25 cm2 in area 
and do not affect 
or slightly affect 
daily life 
5 ~ <10 cm in 
diameter or 25 ~ 
<100 cm2 in area or 
affect daily life 
≥10 cm in 
diameter or ≥100 
cm2 in area or 
ulceration or 
secondary 
infection or 
phlebitis or sterile 
abscess or wound 
drainage or 
seriously affect 
daily life 
Abscess, exfoliative 
dermatitis, dermal or deep 
tissue necrosis 
Rash*, blush ** 
# 
2.5 ~ <5 cm in 
diameter or 6.25 
~ <25 cm2 in area 
and do not affect 
or slightly affect 
daily life 
5 ~ <10 cm in 
diameter or 25 ~ 
<100 cm2 in area or 
affect daily life 
≥10 cm in 
diameter or ≥100 
cm2 in area or 
ulceration or 
secondary 
infection or 
phlebitis or sterile 
abscess or wound 
drainage or 
seriously affect 
daily life 
Abscess, exfoliative 
dermatitis, dermal or deep 
tissue necrosis 
Others 
Pruritus 
Pruritus at the 
vaccination site, 
resolved by itself 
or within 48 
hours after 
treatment 
Pruritus at the 
vaccination site, not 
resolved within 48 
hours after 
treatment  
Affect daily life 
NA 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 101 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Symptoms/signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Cellulitis 
NA 
Need for treatment 
other than injection 
(e.g. oral 
antibacterial, 
antifungal, antiviral 
drugs) 
Need for 
intravenous 
therapy (e.g. 
intravenous 
antibacterial, 
antifungal, 
antiviral drugs) 
Sepsis, or tissue necrosis, 
etc. 
Note: * In addition to directly measuring the diameter for graded evaluation, the progression changes of the 
measurement results should also be recorded. 
** The maximum measured diameter or area should be used. 
#The evaluation and grading of induration and swelling, rash, and blush should be based on the functional level 
and actual measurement results, and select a higher grading index. 
Appendix B. Table 2 
Grading scale for vital signs  
Signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fever* [Axillary 
temperature (ºC)]  
37.3~<38.0 
38.0~<38.5 
38.5~<39.5 
≥39.5 for more than 3 
days 
ECG PR interval 
extension or 
atrioventricular block   
PR interval 0.21 
~ <0.25 seconds 
PR interval 
≥0.25 seconds 
or second-
degree 
atrioventricular 
block type Ⅰ 
Second-degree 
atrioventricular 
block type II 
or ventricular 
interval ≥ 3 
seconds 
Complete atrioventricular 
block 
Signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Heart rate 
Tachycardia (beats/minute) 
101~115 
116~130 
>130 
Arrhythmia requiring 
emergency treatment or 
hospitalization 
Bradycardia 
(beats/minute) 
50~54 
45~49 
<45 
Arrhythmia requiring 
emergency treatment or 
hospitalization 
Blood pressure 
 
 
 
 
Hypertension (mmHg) 
Systolic blood 
pressure: 140 ~ 
<160 or 
diastolic blood 
pressure: 90 ~ 
<100 
Systolic blood 
pressure: ≥160 
~ <180 or 
diastolic blood 
pressure: ≥100 
~ <110 
Systolic blood 
pressure: ≥180 
or diastolic 
blood pressure: 
≥110 
Occurrence of previously 
undiagnosed life-
threatening complications 
(eg malignant 
hypertension) or 
hospitalization 
Hypotension (systolic 
blood pressure) (mmHg) 
85~<89 
80~<85 
<80 
Shock or hospitalization 
Respirator rate 
(times/minute) 
17~20 
21~25 
>25 
Intubation required 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 102 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Note: * Axillary temperature is usually adopted in China, and it can be converted into oral temperature and 
anal temperature if necessary. Generally, oral temperature = axillary temperature + 0.2 ºC; 
Anal temperature = axillary temperature + (0.3 ~ 0.5ºC). When persistent high fever occurs, the cause of high 
fever should be identified as soon as possible.  
Appendix B. Table 3 Grading scale for non-vaccination site (systemic) reactions 
 Organ system 
symptoms/signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Gastrointestinal system 
Diarrhea 
Mild or 
transient, 3 to 
4 times/day, 
abnormal 
fecal 
appearance, 
or mild 
diarrhea 
lasting less 
than 1 week 
Moderate or 
persistent, 5-7 
times/day, abnormal 
fecal appearance, or 
diarrhea> 1 week 
>7 times/day, abnormal 
fecal appearance, or 
hemorrhagic diarrhea, 
orthostatic hypotension, 
electrolyte imbalance, 
needing intravenous 
infusion> 2L 
Hypotension shock, 
needing 
hospitalization 
Constipation* 
Stool softener 
and diet 
adjustment 
needed 
Laxative 
medications needed 
Stubborn constipation 
requiring manual 
defaecation or enema 
Toxic megacolon or 
intestinal 
obstruction 
Dysphagia 
Mild 
discomfort 
when 
swallowing 
Restricted diet 
Diet and conversation are 
very limited; cannot eat 
solid food 
Cannot eat liquid 
food; intravenous 
nutrition needed 
Anorexia 
Loss of 
appetite, food 
intake not 
reduced 
Loss of appetite, 
reduced food intake, 
but no significant 
weight loss 
Loss of appetite and 
significant weight loss 
Intervention needed 
(Such as 
gastrointestinal 
feeding, parenteral 
nutrition) 
Vomiting 
1 ~ 2 times/24 
hours without 
affecting 
activities 
3 ~ 5 times/24 hours 
or limited activity 
> 6 times within 24 hours or 
intravenous fluid therapy 
needed 
Due to hypotensive 
shock, 
hospitalization or 
other means of 
nutrition are 
required 
Nausea 
Transient 
(<24 hours) 
or 
intermittent 
with basically 
normal food 
intake 
Persistent nausea 
leading to reduced 
food intake (24 to 48 
hours) 
Persistent nausea leading to 
almost no food intake (> 48 
hours) or the need for 
intravenous fluid therapy 
Life threatening 
(Such as 
hypotension shock) 
Musculoskeletal and connective tissue 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 103 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
 Organ system 
symptoms/signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Myalgia 
(Non-vaccination 
site) 
Do not affect 
daily 
activities 
Slightly affect daily 
activities 
Severe muscle pain, 
severely affecting daily 
activities 
Emergency 
treatment or 
hospitalization 
Arthritis 
Mild pain, 
accompanied 
by 
inflammation, 
erythema, or 
joint 
swelling; but 
not hindering 
function 
Moderate pain, 
accompanied by 
inflammation, 
erythema, or joint 
swelling; hindering 
function, but not 
affecting daily 
activities 
Severe pain, accompanied 
by inflammation, erythema, 
or joint swelling; affecting 
daily activities 
Permanent and/or 
disabling joint 
damage 
Arthralgia 
Mild pain, not 
hindering 
function 
Moderate pain; 
needing analgesics 
and/or pain 
hindering function, 
but not affecting 
daily activities 
Severe pain; needing 
analgesics and/or pain 
affecting daily activities 
Disabling pain 
Nervous System 
Headache 
Not affecting 
daily 
activities, no 
treatment 
required 
Transient, slightly 
affecting daily 
activities, possibly 
requiring treatment 
or intervention 
Seriously affecting daily 
activities and requiring 
treatment or intervention 
Intractable, 
requiring 
emergency 
treatment or 
hospitalization 
Syncope 
Close to 
syncope, 
without 
losing 
consciousness 
(e.g., pre-
syncope) 
Loss of 
consciousness, but 
no treatment is 
needed 
Loss of consciousness, 
requiring treatment or 
hospitalization 
NA 
New-onset 
convulsions 
NA 
NA 
1 ~ 3 occurrences of 
convulsion 
Prolonged and 
multiple 
occurrences of 
convulsion (e.g., 
convulsion status) 
or difficult to 
control (e.g., 
intractable 
epilepsy) 
Respiratory system 
Cough 
Transient, no 
treatment 
needed 
Continuous cough, 
effective treatment 
Paroxysmal cough, cannot 
be controlled by treatment 
Emergency 
treatment or 
hospitalization 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 104 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
 Organ system 
symptoms/signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Acute 
bronchospasm 
Transient; no 
treatment 
required; 
FEV1% is 
70% to 80% 
Treatment required; 
return to normal 
after bronchodilator 
treatment; FEV1% is 
50% to 70% 
Cannot return to normal 
after bronchodilator 
treatment; FEV1% is 25% to 
50% or continuous 
intercostal depression 
Cyanosis; FEV1% 
<25%; or intubation 
required 
Dyspnea 
Dyspnea 
during 
exercise 
Dyspnea in normal 
activities 
Dyspnea at rest 
Dyspnea, requiring 
oxygen therapy, 
hospitalization or 
assisted breathing 
Organ system 
symptoms/signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Skin and subcutaneous tissue 
Pruritus at the 
non-vaccination 
site 
(No skin damage) 
Slight itching, 
does not 
affect or 
slightly 
affects daily 
life 
Pruritus affecting 
daily life 
Pruritus making daily life 
impossible 
NA 
Abnormal skin 
and mucosa 
Erythema/pru
ritus/color 
change 
Diffuse 
rash/maculopapular 
rash/xerosis/desqua
mation 
Blistering/exudation/desqua
mation/ulceration 
Exfoliative 
dermatitis involving 
mucosa, or 
erythema 
multiforme, or 
suspected Stevens-
Johnsons syndrome 
Mental system 
Insomnia* 
Mild 
difficulty 
falling asleep, 
not affecting 
or slightly 
affecting 
daily life 
Moderate difficulty 
falling asleep, 
affecting daily life 
Severe difficulty falling 
asleep, seriously affecting 
daily life, requiring 
treatment or hospitalization 
NA 
Irritation or 
suppression 
Mild irritation 
or mild 
suppression 
Irritability or 
drowsiness 
Unable to soothe or respond 
poorly 
NA 
Mental disorders 
(Including 
anxiety, 
depression, 
mania, and 
insanity) 
Mild 
symptoms, no 
need to see a 
doctor, or 
behavior does 
not affect or 
slightly 
Have clinical 
symptoms and need 
medical treatment or 
behaviors affect 
daily life 
Need to be hospitalized or 
unable to support daily life 
Have a tendency to 
hurt him/herself or 
others or acute 
mental confusion or 
loss of basic self-
care ability 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 105 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
 Organ system 
symptoms/signs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Detailed 
symptoms should 
be reported 
affects daily 
life 
Immune system 
Acute allergic 
reactions** 
Local 
urticaria 
(blisters), 
requiring no 
treatment 
Local urticaria 
requiring treatment 
or mild angioedema 
requiring no 
treatment 
Extensive urticaria or 
angioedema requiring 
treatment or mild 
bronchospasm 
Allergic shock or 
life-threatening 
bronchospasm or 
laryngeal edema 
Others 
Fatigue, asthenia 
Do not affect 
daily 
activities 
Affect normal daily 
activities 
Seriously affect daily 
activities and cannot work 
Emergency 
treatment or 
hospitalization 
Pain at non-
vaccination site 
(Specify the 
location when 
reporting) 
Mild pain, not 
affecting or 
slightly 
affecting 
daily life 
Pain affecting daily 
life 
Pain making daily life 
impossible 
Disabling pain, loss 
of basic self-care 
ability 
Note: FEV1% refers to forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) 
* For constipation and insomnia, attention should be paid to the changes before and after vaccination. 
** Refers to type I hypersensitivity. 
# Refers to other non-vaccination site pains except muscle pain, arthralgia and headache. 
Appendix B. Table 4 Grading scale for blood biochemistry 
Testing parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Liver function 
(Elevated ALT, AST) 
1.25~<2.5 ×ULN 
2.5~<5.0×ULN 
5.0~<10×ULN 
≥10×ULN 
Elevated total bilirubin 
(mg/dL; µmol/L) 
1.1~<1.6×ULN 
1.6~<2.6×ULN 
2.6~5.0×ULN 
≥5.0×ULN 
Pancreatin (amylase, 
lipase) 
1.1~<1.5×ULN 
1.5~<3.0×ULN 
3.0~<5.0×ULN 
≥5.0×ULN 
Creatine phosphokinase 
(CPK) 
1.25~<1.5×ULN 
1.5~<3.0×ULN 
3.0~<10×ULN 
≥10×ULN 
Hypernatremia (Na, 
mmol/L) 
146~<150 
150~<154 
154~<160 
≥160 
Hyponatremia (Na, 
mmol/L) 
130~<135 
125~<130 
121~<125 
≤120  
Hyperkalemia (K, 
mmol/L) 
5.6~<6.0 
6.0~<6.5 
6.5~<7.0 
≥7.0  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 106 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Testing parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hypokalemia (K, 
mmol/L) 
3.0~<3.4 
2.5~<3.0 
2.0~<2.5  
<2.0  
Hypercalcemia (Ca, 
mmol/L)  
2.65~<2.88 
2.88~<3.13 
3.13~<3.38 
≥3.38 
Hypocalcemia (Ca, 
mmol/L)  
1.95~<2.10 
1.75~<1.95 
1.53~<1.75 
<1.53 
Hyperglycemia (Glu, mmol/L) 
Fasting 
6.11~<6.95 
6.95~<13.89 
13.89~<27.75 
≥27.75 
Non-fasting 
6.44~<8.89 
8.89~<13.89 
13.89~<27.75 
≥27.75 
Hypoglycemia (Glu, 
mmol/L)  
3.05~<3.55 
2.22~<3.05 
1.67~<2.22 
<1.67 
Note: ULN refers to the upper limit of the normal range. 
Appendix B. Table 5 Grading scale for blood routine tests 
Testing 
parameter/Grading 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Increased white blood 
cells (WBC, 109/L) 
11~<13 
13~<15 
15~<30 
≥30 
Decreased white blood 
cells (WBC, 109/L) 
2.000~2.499 
1.500~1.999 
1.000~1.499 
<1.000 
Decreased lymphocytes 
(LY, 109/L) 
0.75~1.00 
0.5~0.749 
0.25~0.49 
<0.25 
Decreased neutrophils 
(ANC, 109/L) 
0.800~1.000 
0.600~0.799 
0.400~0.599 
<0.400 
Eosinophils (Eos, 109/L) 
0.65~1.5 
1.51~5.0 
>5.0 
Hypereosinophilic 
syndrome 
Thrombocytopenia (PLT, 
109/L) 
125~140 
100~124 
25~99 
<25 
Low hemoglobin (g/dL) 
Male 
10.0~10.9 
9.0~<10.0 
7.0~<9.0 
<7.0 
Female 
9.5~10.4 
8.5~<9.5 
6.5~<8.5 
<6.5 
 
 
 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 107 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Appendix B. Table 6 Grading scale for urine routine tests 
Testing parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Urine protein (PRO) 
(Urine test strip testing) 
1+ 
2+ 
3+ or higher 
NA 
Urine glucose 
(Urine test strip testing) 
Trace ~ 1+ 
or ≤250mg 
2+ 
or >250~≤500mg 
>2+ 
or >500mg 
NA 
Red blood cells 
(microscopic 
examination) 
[The number of red 
blood cells (rbc/hpf) 
per high-power field of 
view (excluding female 
menstrual periods)] 
6~<10 
≥10 
Gross hematuria with or 
without blood clots; or 
barrel-type urinary 
erythrocyte; or in need of 
treatment 
Emergency 
treatment or 
hospitalization 
Appendix B. Table 7 General principles for grading of other adverse events 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Mild: Short-term 
(<48h) or slight 
discomfort, which 
does not affect 
activity, and no 
treatment is needed 
Moderate: Mild or 
moderate 
limitation of 
activity, which 
may require 
medical attention, 
does not require or 
only requires mild 
treatment 
Severe: Obviously 
restricted activity, 
requiring medical 
attention and 
treatment, possibly 
requiring 
hospitalization 
Critical: Possibly 
life-threatening; 
serious limitation 
of activity, 
requiring intensive 
care 
Death 
 
Note: refer to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 for 
grading of advrse events thyroid function (T3, T4, thyrotropin) and coagulation function (PT，
APTT，TT，FIB). 
 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 108 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Appendix C FDA Toxicity Grading Scale in Preventive Vaccine Clinical Trials 
These guidelines for toxicity grading scales are primarily intended for healthy adult and adolescent 
volunteers.   
 
Assessment of intensity  
The intensity of AEs or SAEs will be graded by the investigator. For further guidance please refer 
to guideline “US FDA Guidance for Industry. Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials”. Where specific guidance 
for an adverse event term is not provided, the following general approach should be followed:   
• 
Grade 1 - Mild; does not interfere with the subject’s usual function.  
• 
Grade 2 - Moderate; interferes to some extend with the subject’s usual function.  
• 
Grade 3 - Severe; interferes significantly with the subject’s usual function.  
• 
Grade 4 - Potentially Life threatening; life-threatening consequences, urgent intervention 
required.  
Please also refer to the intensity tables given in the guideline for intensity of clinical and laboratory 
abnormalities to be reported as AEs:  
• 
Guideline Section III. A for assessment of clinical abnormalities (local and systemic)  
Local Reactions  
Redness and swelling will be measured and recorded in centimeters and then categorized during 
analysis as absent, mild, moderate, or severe based on the grading scale in Table 1.   
Pain at the injection site will be assessed by the trial subject as absent, mild, moderate, or severe 
according the grading scale in Table 1.   
Appendix C. Table 1 Local reaction grading scale  
  
Mild   
(Grade 1)  
Moderate  
(Grade 2)  
Severe  
(Grade 3)  
Potentially Life Threatening  
(Grade 4)  
Pain at the 
injection site  
Does not interfere 
with activity  
Interferes 
with 
activity  
Prevents 
daily 
activity   
Emergency 
room 
visit 
or 
hospitalization for severe pain  
Redness  
2.5 cm to 5.0 cm   
>5.0 cm to 10.0 cm  >10 cm  
Necrosis 
or 
exfoliative 
dermatitis  
Swelling  
2.5 cm to 5.0 cm   
>5.0 cm to 10.0 cm  >10 cm   
Necrosis  
 Systemic events  
Symptoms of vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain, and new 
or worsened joint pain will be assessed by the participant as absent, mild, moderate, or severe 
according to the grading scale in Table 2.   
Appendix C. Table 2 Systemic event grading scale  
  
Mild   
(Grade 1)  
Moderate 
(Grade 2)  
Severe 
(Grade 3)  
Potentially Life Threatening 
(Grade 4)  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 109 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Vomiting  
1-2 times in 24 h  
>2 times in 24 h  
Requires 
IV 
hydration  
Emergency 
room 
visit 
or 
hospitalization for hypotensive 
shock  
Diarrhea  
2 to 3 loose stools 
in 24 h  
4 to 5 loose stools in  
24 h  
6 or more loose stools 
in 24 h  
Emergency 
room 
visit 
or 
hospitalization 
for 
severe 
diarrhea  
Headache  
Does not interfere 
with activity  
Some 
interference 
with activity  
Prevents daily routine 
activity  
Emergency room visit or  
hospitalization for severe  
headache  
Fatigue/ 
tiredness  
Does not interfere 
with activity  
Some 
interference 
with activity  
Prevents daily routine 
activity  
Emergency 
room 
visit 
or 
hospitalization 
for 
severe 
fatigue  
Chills  
Does not interfere 
with activity  
Some 
interference 
with activity  
Prevents daily routine 
activity  
Emergency 
room 
visit 
or 
hospitalization for severe chills 
New 
or 
worsened 
muscle 
pain  
Does not interfere 
with activity  
Some 
interference 
with activity  
Prevents daily routine 
activity  
Emergency 
room 
visit 
or 
hospitalization for severe new 
or worsened muscle pain  
New 
or 
worsened 
joint pain  
Does not interfere 
with activity  
Some 
interference 
with activity  
Prevents daily routine 
activity  
Emergency 
room 
visit 
or 
hospitalization for severe new 
or worsened joint pain  
  
Fever  
Fever is defined as an oral temperature of ≥38.0°C. Temperature will be measured and recorded 
to 1 decimal place and then categorized during analysis according to the scale shown in Table 3.   
Appendix C. Table 3 Fever grading scale  
  
Mild   
(Grade 1)  
Moderate 
(Grade 2)  
Severe  
(Grade 3)  
Potentially Life Threatening 
(Grade 4)  
Fever  
38.0-38.4°C  
38.5-38.9°C   
39.0-40.0°C  
>40.0°C  
  
Laboratory abnormalities  
Laboratory abnormalities will be graded according to the grading scheme given in Table 4.  
Appendix C Table 4: Laboratory abnormality grading scale  
Hematology   
Mild (Grade 1)   
Moderate  
(Grade 2)   
Severe (Grade 3)   
Potentially Life   
Threatening (Grade 
4)  
Hemoglobin (Female) 
- g/dL   
11.0 – 12.0   
9.5 – 10.9   
8.0 – 9.4   
<8.0   
Hemoglobin (Female) 
change from baseline 
value - g/dL   
Any decrease – 1.5   
1.6 – 2.0   
2.1 – 5.0   
>5.0   

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 110 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Hematology   
Mild (Grade 1)   
Moderate  
(Grade 2)   
Severe (Grade 3)   
Potentially Life   
Threatening (Grade 
4)  
Hemoglobin  
(Male) - g/dL   
12.5 – 13.5   
10.5 – 12.4   
8.5 – 10.4   
<8.5   
Hemoglobin  
(Male)   
change from baseline 
value – g/dL   
Any decrease – 1.5   
1.6 – 2.0   
2.1 – 5.0   
>5.0   
WBC 
increase 
- 
cells/mm3  
10,800 – 15,000   
15,001 – 20,000   
20,001 – 25, 000   
>25,000   
WBC 
decrease 
- 
cells/mm3  
2,500 – 3,500   
1,500 – 2,499   
1,000 – 1,499   
<1,000   
Lymphocytes 
decrease - cells/mm3  
750 – 1,000   
500 – 749   
250 – 499   
<250   
Neutrophils decrease - 
cells/mm3  
1,500 – 2,000   
1,000 – 1,499   
500 – 999   
<500   
Eosinophils 
- 
cells/mm3  
650 – 1500   
1501 - 5000   
>5000   
Hypereosinophilic   
Platelets decreased - 
cells/mm3  
125,000 – 140,000   
100,000 – 124,000  25,000 – 99,000   
<25,000   
Chemistry  
Mild (Grade 1)   
Moderate  
(Grade 2)   
Severe  (Grade 3)   
Potentially Life   
Threatening  
(Grade 4)   
BUN - mg/dL   
23 – 26   
27 – 31   
> 31   
Requires dialysis   
Creatinine – mg/dL   
1.5 – 1.7   
1.8 – 2.0   
2.1 – 2.5   
> 
2.5 
or 
requires 
dialysis   
Alkaline phosphate – 
increase by factor   
1.1 – 2.0 x ULN   
2.1 – 3.0 x ULN   3.1 – 10 x ULN   
>10 x ULN   
Liver function tests 
– 
ALT, 
AST  
increase by factor   
1.1 – 2.5 x ULN   
2.6 – 5.0 x ULN   5.1 – 10 x ULN   
>10 x ULN   
Hematology   
Mild (Grade 1)   
Moderate  
(Grade 2)   
Severe (Grade 3)   
Potentially Life   
Threatening (Grade 
4)  
Bilirubin – when 
accompanied  by 
any increase in 
liver function test 
-  increase by 
factor   
1.1 – 1.25 x ULN   
1.26 – 1.5 x ULN   1.51 – 1.75 x ULN   
>1.75 x ULN   
Bilirubin – when liver 
function test is normal 
- increase by factor   
1.1 – 1.5 x ULN   
1.6 – 2.0 x ULN   2.0 – 3.0 x ULN   
>3.0 x ULN   
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; ULN = upper limit 
of normal; WBC = white blood cell.  

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 111 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Appendix D Collection and Processing of Throat Swab Specimens 
The sampled person gargles with normal saline first, and the sampling person puts the swab in 
sterile normal saline to moisten it (it is forbidden to put the swab in the virus preserving fluid to 
avoid allergy caused by antibiotics). The sampled person slightly raises the head, opens the mouth 
widely and says "ah” to expose the pharyngeal tonsils on both sides. Pass the swab over the root 
of tongue, and wipe the pharyngeal tonsils on both sides of the sampled person with a little bit 
strength for at least 3 times back and forth. Then wipe up and down the posterior pharyngeal wall 
for at least 3 times, immerse the swab head into a tube containing 2 ~ 3 mL of virus preserving 
fluid (isotonic saline solution, tissue culture solution or phosphate buffer solution can also be used), 
discard the tail end, and tighten the cap. 
Specimens are packed in the biosafety cabinet of a Biological Safety Level 2 laboratory after 
collection. All specimens should be placed in a freezing-resistant sample collection tube of 
suitable size with a screw cap and an inner gasket, and tightened. The sample number, type, name 
and sampling date are indicated on the outside of the container. Specimens should be sent to the 
laboratory as soon as possible after collection and tested as soon as possible. Specimens that can 
be tested within 24 hours can be stored at 4 °C; specimens that cannot be tested within 24 hours 
should be stored at -70 °C or below.

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 112 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
Appendix E Protocol amendments 
Main Changes from Version 2.0 to Version 3.0 
In-text location 
(Section) 
Before 
After 
Rationale 
Page header, the first 
page, synopsis 
Version 2.0 
Date: 10 JUL 2020 
Version 3.0 
Date: 5 AUG 2020 
Version change 
Synopsis, Section 
10.1.2, 10.2.1, 
10.2.2 
Solicited adverse event 
Solicited reaction 
Change wording 
Synopsis, Section 
4.2.6, 6.1, 7.2  
Age range for elderly subjects: >55 years 
old 
≥65 years old and ≤85 years old  
Consistent with the 
age range of the 
elderly subjects in 
Germany and US 
trials. 
Synopsis, Section 
9.1.6 
Blood samples for humoral immunity 
(antibody) in adult group will be collected 
at Visit 1 (prior to prime vaccination) and 
Visits 3, 5 (prior to boost vaccination), 6, 
8, 10, 11, 12. 
Blood samples for humoral 
immunity (antibody) in adult group 
will be collected at Visit 1 (prior to 
prime vaccination) and Visits 5 
(prior to boost vaccination), 6, 8, 10, 
11, 12. 
According to the 
preliminary 
immunogenicity data 
of Germany and US 
trials. 
Synopsis, Section 
7.2 
Exclusion criteria for elderly subjects:  
1. Physical examination and qualifying 
screening during screening visits, finding 
baseline laboratory abnormalities ≥grade 
1. Physical examination and 
qualifying screening during 
screening visits, finding baseline 
laboratory abnormalities ≥grade 3 
(for hematology abnormalities 
According to the 
preliminary safety 
data of Germany and 
US trials. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 113 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
3 (according to grading criteria in 
Appendix B). 
with Grade ≥2, according to 
grading criteria in Appendix B). 
Synopsis, Table 2  
Screening period: 7 days. 
Screening period: 14 days. 
Delay for IMP 
import 
Section 6.6  
During the time of enrollment into a given 
cohort, if any of the following events 
occur and are assessed to be vaccine 
related, further vaccination in that cohort 
will be stopped: 
• 
Anaphylaxis reaction considered 
related; 
• 
Generalized urticaria considered 
related; 
• 
1/3 trial subjects in that cohort with 
any severe unsolicited local reaction, 
if considered related and not 
manageable with simple measures 
(e.g. cooling, analgesia, nonsteroidal 
anti-inflammatory drugs [NSAID]; 
• 
Any possibly related AEs within 7 
days of vaccination assessed to be 
potentially life-threatening (Grade 4);  
• 
Any systemic SAE within 7 days of 
vaccination considered related;  
• 
Any fever >40.0°C (>104.0°F) within 
7 days of vaccination considered 
related;  
During the time of enrollment into a 
given cohort, if any of the following 
events occur and are assessed to be 
vaccine related, further vaccination 
in that cohort will be suspended: 
• 
Anaphylaxis reaction 
considered related; 
• 
Generalized urticaria 
considered related; 
• 
1/3 trial subjects in that cohort 
with any severe unsolicited 
local reaction, if considered 
related and not manageable 
with simple measures (e.g. 
cooling, analgesia, nonsteroidal 
anti-inflammatory drugs 
[NSAID]; 
• 
Any possibly related AEs 
within 7 days of vaccination 
assessed to be potentially life-
threatening (Grade 4);  
According to the 
preliminary safety 
data of Germany and 
US trials. 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 114 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
• 
15% trial subjects with the severe 
(Grade 3) AE (including laboratory 
abnormalities with clinical 
manifestations) within 7 days of 
vaccination, considered vaccine 
related. 
• 
Any systemic SAE within 7 
days of vaccination considered 
related;  
• 
Any fever >40.0°C (>104.0°F) 
within 7 days of vaccination 
considered related;  
• 
Occurence of grade ≥3 
adverse events that lasted at 
least 48 h and associated with 
vaccination, and for which 
there is no alternative feasible 
explanation, in more than 
20% of participants (except 
local reactions: 
pain/tenderness, 
erythema/redness, and 
induration/swelling) after 
primary or booster 
inoculation; 
• 
Occurence of grade ≥3 clinical 
laboratory abnormality 
related adverse events with 
clinical manifestations, that 
not recovered for at least 8 
days and associated with 
vaccination, and for which 
there is no alternative feasible 
explanation, in more than 
20% of participants after 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 115 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
primary or booster 
inoculation. 
Section 6.7 
Individuals with a clinically significant 
active infection (as assessed by the 
investigator) or axillary temperature 
≥37.3°C or oral temperature ≥38.0°C, 
within 3 days after intended 
investigational vaccine/placebo 
vaccination. 
Individuals with a clinically 
significant active infection (as 
assessed by the investigator) or 
axillary temperature ≥37.3°C or oral 
temperature ≥38.0°C, within 3 days 
before intended investigational 
vaccine/placebo vaccination. 
Typo 
Synopsis, Section 
5.2.1, 10.1.2 
pain, tenderness 
pain/tenderness 
According to the 
Guidance for 
Adverse Events 
Grading Scale 
Synopsis, Section 
5.1.3, 5.2.3 
Exploratory endpoints: 
 
 
 
Exploratory endpoints: 
 
 
 
 
The lab test item 
change 
 
 

SARS-CoV-2 mRNA Vaccine 
  
Trial No. BNT162-03 
Page 116 of 116   
Protocol Amd 3, Version 3.0  
5 AUG 2020 
  
Confidential  
15.0 
References 
1 
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 
2020. 579(7798): 270-273. 
2 
Qiu J. Covert coronavirus infections could be seeding new outbreaks. Nature. 2020 . 
3 
Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N 
Engl J Med. 2020. 382(13): 1199-1207. 
4 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019. 
5 
Mark J. Mulligan1 KEL, Nicholas Kitchin JA, Alejandra Gurtman SL, et al. Phase 1/2 Study to Describe the Safety and 
Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. 
medRxiv. 2020 . 
6 
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus 
origins and receptor binding. Lancet. 2020. 395(10224): 565-574. 
7 
Rauch S, Jasny E, Schmidt KE, Petsch B. New Vaccine Technologies to Combat Outbreak Situations. Front Immunol. 2018. 
9: 1963. 
8 
Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics--developing a new class of drugs. Nat Rev Drug Discov. 2014. 
13(10): 759-80. 
9 
Vogel AB, Lambert L, Kinnear E, et al. Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to 
mRNA Vaccines but at Much Lower Doses. Mol Ther. 2018. 26(2): 446-455. 
10 
Moyo N, Vogel AB, Buus S, et al. Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines 
Delivered as Self-Amplifying mRNA. Mol Ther Methods Clin Dev. 2019. 12: 32-46. 
11 
 
Pardi N, Hogan MJ, Pelc RS, et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. 
Nature. 2017. 543(7644): 248-251. 
12 
1Feldman RA, Fuhr R, Smolenov I, et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential 
are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine. 2019. 37(25): 3326-
3334