Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-nCoV Vaccine (mRNA-1273) in Healthy Adults
Phase: PHASE1
Conditions: COVID-19, COVID-19 Immunisation
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

DMID Protocol 20-0003 
Version 7.0 
mRNA-1273 
 
30 July 2021 
 
DMID/NIAID/NIH 
CONFIDENTIAL 
Page 1 of 116 
 
Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-nCoV 
Vaccine (mRNA-1273) in Healthy Adults 
 
DMID Protocol Number: 20-0003 
 
IND Sponsor: Division of Microbiology and Infectious Diseases (DMID) 
 
Version Number: 7.0 
 
30 July 2021 
 
 
 

DMID Protocol 20-0003 
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mRNA-1273 
 
30 July 2021 
 
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STATEMENT OF COMPLIANCE 
Each institution engaged in this research will hold a current Federal wide Assurance (FWA) 
issued by the Office of Human Research Protection (OHRP) for federally funded research. The 
Institutional Review Board (IRB)/Independent or Institutional Ethics Committee (IEC) must be 
registered with OHRP as applicable to the research. 
 
The study will be carried out in accordance with the following as applicable: 
• United States (US) Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of 
Human Subjects 
• Food and Drug Administration (FDA) Regulations: 21 CFR Part 50 (Protection of 
Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical Investigators), 21 
CFR Part 56 (IRBs), 21 CFR Part 11, and 21 CFR Part 312 (Investigational New Drug 
Application), and/or 21 CFR 812 (Investigational Device Exemptions) 
• The International Council for Harmonisation (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH) E6(R2) Good Clinical Practice 
(GCP), and the Belmont Report: Ethical Principles and Guidelines for the Protection of 
Human Subjects of Research, Report of the National Commission for the Protection of 
Human Subjects of Biomedical and Behavioral Research 
• The policies and procedures of National Institutes of Health (NIH) Office of Extramural 
Research and Division of Microbiology and Infectious Diseases (DMID) 
• The National Institute of Allergy and Infectious Diseases (NIAID) Terms of Award 
• Any additional Federal, State, and Local Regulations and Guidance 
 
The signature below provides the necessary assurance that this study will be conducted 
according to all stipulations of the protocol, including statements regarding confidentiality, and 
according to local legal and regulatory requirements, US federal regulations, and ICH E6(R2) 
GCP guidelines. 
 
Site Investigator Signature: 
 
 
Signed: 
 
Date: 
 
 
Name, Credentials 
Title 
 
 
 
 
 

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TABLE OF CONTENTS 
1. 
PROTOCOL SUMMARY ........................................................................................................... 8 
1.1 
Synopsis ................................................................................................................................ 8 
1.2 
Schedule of Activities (SOA) ............................................................................................ 16 
2. 
INTRODUCTION ...................................................................................................................... 17 
2.1 
Background and Study Rationale ...................................................................................... 17 
2.1.1 
Public Readiness and Emergency Preparedness Act ............................................... 20 
2.2 
Risk/Benefit Assessment ................................................................................................... 21 
2.2.1 
Known Potential Risks .............................................................................................. 21 
2.2.2 
Known Potential Benefits.......................................................................................... 26 
3. 
OBJECTIVES AND ENDPOINTS .......................................................................................... 26 
4. 
STUDY DESIGN ....................................................................................................................... 28 
4.1 
Overall Design.................................................................................................................... 28 
4.2 
Scientific Rationale for Study Design .............................................................................. 31 
4.3 
Justification for Dose ......................................................................................................... 31 
4.4 
Optional Third mRNA-1273 Vaccination Substudy........................................................ 31 
5. 
STUDY POPULATION ............................................................................................................ 32 
5.1 
Inclusion Criteria ................................................................................................................ 32 
5.1.1 
Leukapheresis Inclusion Criteria .............................................................................. 34 
5.2 
Exclusion Criteria............................................................................................................... 35 
5.2.1 
Exclusion of Specific Populations ............................................................................ 37 
5.3 
Inclusion of Vulnerable Subjects ...................................................................................... 37 
5.4 
Lifestyle Considerations .................................................................................................... 37 
5.5 
Screen Failures ................................................................................................................... 38 
5.6 
Strategies for Recruitment and Retention ......................................................................... 38 
5.6.1 
Recruitment ................................................................................................................ 38 
5.6.2 
Retention .................................................................................................................... 38 
5.6.3 
Compensation Plan for Subjects ............................................................................... 38 
5.6.4 
Costs ........................................................................................................................... 39 
6. 
STUDY PRODUCT ................................................................................................................... 39 
6.1 
Study Product(s) and Administration ............................................................................... 39 
6.1.1 
Study Product Description ........................................................................................ 39 
6.1.2 
Dosing and Administration ....................................................................................... 39 
6.1.3 
Dose Escalation.......................................................................................................... 40 
6.1.4 
Dose Modifications.................................................................................................... 41 
6.2 
Accountability/Handling/Storage/Preparation ................................................................. 41 
6.2.1 
Acquisition and Accountability ................................................................................ 41 
6.2.2 
Formulation, Appearance, Packaging, and Labeling............................................... 42 
6.2.3 
Product Storage and Stability.................................................................................... 43 
6.2.4 
Preparation ................................................................................................................. 43 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................................. 44 

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6.3.1 
Treatment Assignment Procedures ........................................................................... 44 
6.3.2 
Randomization and Blinding .................................................................................... 44 
6.3.3 
Blinding and Masking Procedures ............................................................................ 44 
6.4 
Study Intervention Compliance ......................................................................................... 45 
6.5 
Concomitant Therapy ........................................................................................................ 45 
6.5.1 
Rescue Medicine ........................................................................................................ 45 
6.5.2 
Non-Research Standard of Care ............................................................................... 45 
7. 
STUDY INTERVENTION DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................................... 45 
7.1 
Halting Criteria and Discontinuation of Study Intervention ........................................... 45 
7.1.1 
Halting Criteria .......................................................................................................... 45 
7.1.2 
Sentinel Halting Criteria............................................................................................ 46 
7.1.3 
Criteria for Continuation of Dosing and Redosing .................................................. 46 
7.1.3.1 
Withdrawal Criteria for Second Study Vaccination ............................................ 46 
7.1.3.2 
Delay of Study Vaccination .................................................................................. 47 
7.1.4 
Follow-up for Subjects that Discontinued Study Intervention ............................... 47 
7.2 
Subject Withdrawal from the Study and Replacement .................................................... 48 
7.3 
Lost to Follow-Up .............................................................................................................. 49 
8. 
STUDY ASSESSMENTS AND PROCEDURES ................................................................... 49 
8.1 
Screening and Immunogenicity Assessments .................................................................. 49 
8.1.1 
Screening Procedures ................................................................................................ 49 
8.1.2 
Screening Procedures for Leukapheresis ................................................................. 51 
8.1.3 
Immunogenicity Evaluations .................................................................................... 51 
8.1.4 
Samples for Genetic/Genomic Analysis................................................................... 51 
8.1.4.1 
Genetic/Genomic Analysis ................................................................................... 51 
8.1.4.2 
Genetic Privacy and Confidentiality .................................................................... 51 
8.1.4.3 
Management of Results ......................................................................................... 52 
8.2 
Safety and Other Assessments .......................................................................................... 52 
8.2.1 
Procedures to be Followed in the Event of Abnormal Clinical Laboratory Test 
Values or Abnormal Clinical Findings ..................................................................................... 57 
8.3 
Adverse Events and Serious Adverse Events ................................................................... 57 
8.3.1 
Definition of Adverse Event (AE) ............................................................................ 57 
8.3.1.1 
Solicited Adverse Events ...................................................................................... 57 
8.3.1.2 
Unsolicited Adverse Events .................................................................................. 58 
8.3.1.3 
Possible Adverse Events Associated with Leukapheresis .................................. 58 
8.3.1.4 
Special Reporting of Adverse Events ................................................................... 59 
8.3.2 
Definition of Serious Adverse Event (SAE) ............................................................ 59 
8.3.3 
Suspected Unexpected Serious Adverse Reactions (SUSAR)................................ 59 
8.3.4 
Classification of an Adverse Event .......................................................................... 59 
8.3.4.1 
Severity of Adverse Events ................................................................................... 60 
8.3.4.2 
Relationship to Study Intervention ....................................................................... 60 
8.3.5 
Time Period and Frequency for Event Assessment and Follow-Up ...................... 60 
8.3.6 
Adverse Event Reporting .......................................................................................... 61 
8.3.6.1 
Investigators Reporting of AEs ............................................................................ 61 

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8.3.7 
Serious Adverse Event Reporting ............................................................................. 61 
8.3.7.1 
Investigators Reporting of SAEs .......................................................................... 61 
8.3.7.2 
Regulatory Reporting of SAEs ............................................................................. 61 
8.3.8 
Reporting Events to Subjects .................................................................................... 62 
8.3.9 
Adverse Events of Special Interest (AESIs) ............................................................ 62 
8.3.10 
Reporting of Pregnancy ............................................................................................. 63 
8.4 
Unanticipated Problems ..................................................................................................... 63 
8.4.1 
Definition of Unanticipated Problems (UPs) ........................................................... 63 
8.4.2 
Unanticipated Problem Reporting ............................................................................ 63 
8.4.3 
Reporting Unanticipated Problems to Subjects ....................................................... 63 
9. 
STATISTICAL CONSIDERATIONS ...................................................................................... 64 
9.1 
Statistical Hypotheses ........................................................................................................ 64 
9.2 
Sample Size Determination ............................................................................................... 64 
9.3 
Populations for Analyses ................................................................................................... 65 
9.4 
Statistical Analyses ............................................................................................................ 66 
9.4.1 
General Approach ...................................................................................................... 66 
9.4.2 
Analysis of the Primary Endpoint(s) ........................................................................ 66 
9.4.3 
Analysis of the Secondary Endpoint(s) .................................................................... 66 
9.4.4 
Safety Analyses.......................................................................................................... 66 
9.4.5 
Baseline Descriptive Statistics .................................................................................. 67 
9.4.6 
Planned Interim and Early Analyses ........................................................................ 67 
9.4.6.1 
Interim Safety Analyses ........................................................................................ 67 
9.4.6.2 
Interim Immunogenicity Review .......................................................................... 68 
9.4.6.3 
Interim Immunogenicity and Safety Review ....................................................... 68 
9.4.7 
Sub-Group Analyses .................................................................................................. 68 
9.4.8 
Tabulation of Individual Subject Data ..................................................................... 68 
9.4.9 
Exploratory Analyses ................................................................................................ 69 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .... 69 
10.1 
Regulatory, Ethical, and Study Oversight Considerations .............................................. 69 
10.1.1 
Informed Consent Process......................................................................................... 69 
10.1.1.1 
Requirements for Permission by Parents/Guardians and Assent by Children 
(in case of a minor) ................................................................................................................ 71 
10.1.1.2 
Other Informed Consent Procedures ................................................................ 71 
10.1.2 
Study Termination and Closure ................................................................................ 72 
10.1.3 
Confidentiality and Privacy....................................................................................... 73 
10.1.4 
Secondary Use of Stored Specimens and Data ........................................................ 74 
10.1.4.1 
Samples for Secondary Research ..................................................................... 74 
10.1.4.2 
Data Sharing for Secondary Research ............................................................. 75 
10.1.5 
Key Roles and Study Governance ............................................................................ 75 
10.1.6 
Safety Oversight ........................................................................................................ 75 
10.1.6.1 
Protocol Team Oversight .................................................................................. 75 
10.1.6.2 
Safety Monitoring Committee (SMC) ............................................................. 76 
10.1.7 
Clinical Monitoring ................................................................................................... 76 
10.1.8 
Quality Control (QC) and Quality Assurance (QA) ................................................ 77 

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10.1.9 
Data Handling and Record Keeping ......................................................................... 77 
10.1.9.1 
Data Collection and Management Responsibilities ........................................ 77 
10.1.9.2 
Study Record Retention .................................................................................... 78 
10.1.9.3 
Source Records .................................................................................................. 78 
10.1.10 Protocol Deviations ................................................................................................... 78 
10.1.11 Publication and Data Sharing Policy ........................................................................ 79 
10.1.12 Human Data Sharing Plan ......................................................................................... 79 
10.1.13 Genomic Data Sharing (GDS) Plan .......................................................................... 79 
10.1.14 Publication.................................................................................................................. 79 
10.1.15 Conflict of Interest Policy ......................................................................................... 79 
10.2 
Additional Considerations ................................................................................................. 80 
10.2.1 
Research Related Injuries .......................................................................................... 80 
10.3 
Abbreviations ..................................................................................................................... 80 
10.4 
Protocol Amendment History ............................................................................................ 83 
11. 
REFERENCES ....................................................................................................................... 93 
12. 
APPENDIX A: OPTIONAL THIRD mRNA-1273 VACCINATION SUBSTUDY ........ 98 
12.1 
Overview............................................................................................................................. 98 
12.2 
Background and Scientific Rationale................................................................................ 98 
12.2.1 
Justification for Dose ............................................................................................... 101 
12.3 
Risk/Benefit Assessment ................................................................................................. 101 
12.3.1 
Known Potential Risks ............................................................................................ 101 
12.3.2 
Known Potential Benefits........................................................................................ 102 
12.4 
Objectives and Endpoints ................................................................................................ 102 
12.5 
Study Design .................................................................................................................... 104 
12.6 
Eligibility Criteria ............................................................................................................ 108 
12.6.1 
Inclusion Criteria ..................................................................................................... 108 
12.6.2 
Exclusion Criteria .................................................................................................... 108 
12.7 
Study Product ................................................................................................................... 109 
12.7.1 
Study Product Description ...................................................................................... 109 
12.7.2 
Dose Modifications.................................................................................................. 110 
12.7.3 
Product Storage and Stability.................................................................................. 110 
12.8 
Concomitant Therapy ...................................................................................................... 111 
12.9 
Immunogenicity Evaluations ........................................................................................... 111 
12.10 Adverse Events and Serious Adverse Events ................................................................. 111 
12.10.1 Reporting of Adverse Events .................................................................................. 111 
12.10.2 Reporting of Pregnancy ........................................................................................... 112 
12.10.3 Unanticipated Problem Reporting .......................................................................... 112 
12.11 Statistical Considerations ................................................................................................ 112 
12.11.1 Statistical Hypotheses .............................................................................................. 112 
12.11.2 Sample Size Determination ..................................................................................... 112 
12.11.3 Populations for Analyses ......................................................................................... 113 
12.11.4 Statistical Analyses .................................................................................................. 113 
12.11.5 General Approach .................................................................................................... 113 
12.11.6 Analysis of the Primary Endpoint(s) ...................................................................... 113 
12.11.7 Analysis of the Secondary Endpoint(s) .................................................................. 114 

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12.11.8 Safety Analyses........................................................................................................ 114 
12.11.9 Baseline Descriptive Statistics ................................................................................ 114 
12.11.10 Planned Interim and Early Analyses ...................................................................... 115 
12.11.10.1 Interim Safety Analyses ................................................................................. 115 
12.11.10.2 Interim Immunogenicity Review ................................................................... 115 
12.11.10.3 Interim Immunogenicity and Safety Review ................................................ 115 
12.11.11 Sub-Group Analyses ................................................................................................ 115 
12.11.12 Tabulation of Individual Subject Data ................................................................... 115 
12.11.13 Exploratory Analyses .............................................................................................. 115 
12.12 Regulatory, Ethical, and Study Oversight Considerations ............................................ 116 
 
LIST OF TABLES 
Table 1: Treatment Arms ..................................................................................................................... 8 
Table 2: Objectives and Endpoints (Outcome Measures) ................................................................ 11 
Table 3: Dosing and Administration ................................................................................................. 15 
Table 4: Schedule of Activities for the Main Study ......................................................................... 16 
Table 5: Objectives and Endpoints (Outcome Measures) ................................................................ 26 
Table 6: Treatment Arms ................................................................................................................... 28 
Table 7: Dosing and Administration ................................................................................................. 39 
Table 8: Venipuncture Volumes ........................................................................................................ 55 
Table 9: Probability of Observing an Adverse Event for Various Event Rates ............................. 64 
Table 10: Abbreviations ..................................................................................................................... 80 
Table 11: Protocol Amendment History ........................................................................................... 83 
Table 12: Objectives and Endpoints (Outcome Measures) ............................................................ 102 
Table 13: Treatment Arms and Substudy Dosing........................................................................... 105 
Table 14: Schedule of Activities for the Optional Third mRNA-1273 Vaccination Substudy ... 107 
 
 
LIST OF FIGURES 
Figure 1. The SARS-CoV-2 full-length stabilized spike protein (S-2P) delivered by mRNA is 
expressed on the cell surface .............................................................................................................. 20 
 
 
 

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1. 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Rationale for Proposed Clinical Study 
In December 2019 the Wuhan Municipal Health Committee identified an outbreak of viral 
pneumonia cases of unknown cause. Coronavirus ribonucleic acid (RNA) was quickly identified 
in some of these patients. On January 5, 2020 there were 59 confirmed cases, 278 cases on 
January 20, rising to more than 110,000 confirmed cases and 3996 deaths as of March 9, 2020. 
On March 11, 2020 the World Health Organization (WHO) declared Coronavirus disease 2019 
(COVID-19) a pandemic. SARS-CoV-2 has continued to spread globally with cases being 
reported in at least 216 countries, and as of May 14, 2020, 4,307,287 confirmed cases and 
295,101 deaths had been reported to the WHO. There is currently no vaccine against the 2019-
novel Coronavirus (2019-nCoV; SARS-CoV-2). Therefore, there is an urgent public health need 
for rapid development of novel interventions. 
ModernaTX, Inc. has developed a rapid response, proprietary messenger RNA (mRNA)-based 
vaccine platform. This is based on the principle and observations that antigens can be produced 
in vivo by delivery and uptake of the corresponding mRNA by cells. ModernaTX, Inc. is using 
its mRNA-based technology to develop a novel lipid nanoparticle (LNP)-encapsulated 
messenger RNA (mRNA)-based vaccine against SARS-CoV-2 (mRNA-1273). Prior preclinical 
studies have demonstrated that coronavirus spike (S) proteins are immunogenic and S protein-
based vaccines, including deoxyribonucleic acid (DNA) and mRNA delivery platforms, are 
protective in animals. Prior clinical trials of vaccines targeting related coronaviruses and other 
viruses have demonstrated that DNA and mRNA-based vaccines are safe and immunogenic. It is 
therefore anticipated that mRNA-1273 will generate robust immune responses to the SARS-
CoV-2 S protein. 
Based on currently available information and clinical experience suggesting that older adults 
may be at higher risk for severe illness from COVID-19, it is important to rapidly assess clinical 
safety of novel vaccines in this vulnerable population as early as possible. Thus, this phase I 
clinical trial proposes to evaluate the safety and immunogenicity of different dosages of 
Moderna’s mRNA-1273 in healthy adults across the age spectrum (≥18 years of age). 
Study Design 
This is a phase I, open-label, dose-ranging clinical trial in males and non-pregnant females, ≥18 
years of age, who are in good health and meet all eligibility criteria. This clinical trial is designed 
to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by 
ModernaTX, Inc. mRNA-1273 is a novel LNP-encapsulated mRNA-based vaccine that encodes 
for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at 
up to three domestic clinical research sites. 
Table 1: Treatment Arms 
Cohort 
Sample Size 
Stratum 
(Years of Age) 
First and Second Dose 
1 
15 
18-55 
25 mcg mRNA-1273 

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Cohort 
Sample Size 
Stratum 
(Years of Age) 
First and Second Dose 
2 
15 
18-55 
100 mcg mRNA-1273 
3 
15 
18-55 
250 mcg mRNA-1273 
4 
10 
56-70 
25 mcg mRNA-1273 
5 
10 
56-70 
100 mcg mRNA-1273 
6* 
10 
56-70 
250 mcg mRNA-1273 
7 
10 
≥71 
25 mcg mRNA-1273 
8 
10 
≥71 
100 mcg mRNA-1273 
9* 
10 
≥71 
250 mcg mRNA-1273 
10 
15 
18-55 
50 mcg mRNA-1273 
11 
10 
56-70 
50 mcg mRNA-1273 
12 
10 
≥71 
50 mcg mRNA-1273 
13* 
15 
18-55 
10 mcg mRNA-1273 
*Cohorts 6, 9 and 13 were not enrolled. 
Up to one hundred and fifty-five (155) subjects will be enrolled into one of thirteen cohorts (10 
micrograms [mcg], 25 mcg, 50 mcg, 100 mcg, or 250 mcg). Subjects will receive an 
intramuscular (IM) injection (0.5 milliliters [mL]) of mRNA-1273 on Days 1 and 29 in the 
deltoid muscle and will be followed through 12 months post second vaccination (Day 394). The 
second dose of vaccine (0.5 mL) will be administered preferably in the same arm used for the 
first dose. 
Follow-up visits will occur 1, 2 and 4 weeks post each vaccination (Days 8, 15, 29, 36, 43, and 
57), as well as 3, 6 and 12 months post second vaccination (Days 119, 209 and 394). 
Reactogenicity will be assessed at these visits, as well as blood will be drawn for 
immunogenicity assays. Additional safety and reactogenicity data will be solicited via telephone 
calls to subjects 1 and 2 days post each vaccination (Days 2, 3, 30, and 31). 
To determine early safety signals for this phase I clinical trial, vaccination will proceed in a 
staged fashion. Sentinel subject dosing will begin with 4 subjects in cohort 1 (25 mcg). The 4 
sentinel subjects for cohort 2 (100 mcg) will be enrolled no earlier than one day after enrollment 
of the last of the 4 sentinel subjects in cohort 1. If no halting rules have been met after the 8 
sentinel subjects have completed Day 5, then full enrollment will proceed first with the 
remaining subjects in cohort 1, followed by the remaining subjects in cohort 2 without 

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interruption. If no halting rules have been met after all subjects in cohort 2 have completed Day 
8, then dosing of 4 sentinel subjects will begin in cohort 3. If no halting rules have been met after 
the 4 sentinel subjects in cohort 3 have completed Day 5, then full enrollment of cohort 3 will 
proceed. 
If no halting rules have been met after all subjects in cohorts 1 and 2 have completed Day 8, 
dosing will begin for cohorts 4 (25 mcg; 56-70 years of age) and 5 (100 mcg; 56-70 years of 
age). If no halting rules have been met after all subjects in cohorts 4 and 5 have completed Day 
8, dosing will begin for cohorts 7 (25 mcg; ≥71 years of age) and 8 (100 mcg; ≥71 years of age). 
Based on the interim immunogenicity data available as of May 15, 2020, enrollment into cohorts 
6 and 9 (250 mcg; 56-70 years of age and ≥71 years of age) will be deferred in order to explore 
lower dosages. Therefore, enrollment of cohorts 10-12 (50 mcg; 18-55 years of age, 56-70 years 
of age and ≥71 years of age) will be prioritized. Subjects will be enrolled simultaneously in 
cohorts 10-12; there will be no staging. To further explore dosage sparing, cohort 13 (10 mcg 
dose; 18-55 years of age) may be enrolled. A decision regarding the enrollment of cohorts 6, 9 
and 13 will be made after review of interim immunogenicity data from cohorts 1-5, 7, 8, and 10-
12. 
If no halting rules have been met after all subjects in cohorts 5 and 8 have completed Day 8, 
dosing will begin concurrently for cohorts 10-12. If no halting rules have been met after all 
subjects in cohorts 3, 7 and 8 have completed Day 8, dosing may begin for cohort 6, if enrolled. 
If no halting rules have been met after all subjects in cohort 6 have completed Day 8, dosing may 
begin for cohort 9, if enrolled. 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of each vaccination through 7 days post each vaccination. Unsolicited 
non-serious adverse events (AEs) will be collected from the time of each vaccination through 28 
days post each vaccination. Serious adverse events (SAEs), protocol specified adverse events of 
special interest (AESIs), new-onset chronic medical conditions (NOCMCs), and medically-
attended adverse events (MAAEs) will be collected through 12 months after the second 
vaccination (Day 394). 
Clinical safety laboratory evaluations will be performed at screening, as well as immediately 
prior to and 7 days post each vaccination (Days 1, 8, 29, and 36). 
To support development of diagnostics, therapeutics and vaccines, a subset of subjects enrolled 
in cohorts 2, 3, 5, 10, and 11 may undergo leukapheresis to collect additional samples for 
secondary research. If enrollment in cohort 6 proceeds, a subset of subjects in this cohort may 
also undergo leukapheresis. 
Based on interim immunogenicity and reactogenicity data, Cohorts 6, 9 and 13 were not 
enrolled. 
During the course of this clinical trial, interim efficacy data from a Phase 3 placebo-controlled 
clinical trial of mRNA-1273 (COVE), administered as 2 doses of 100 mcg given 28 days apart, 
demonstrated vaccine efficacy of 94.1% (95% CI: 89.3%, 96.8%) for the prevention of 
symptomatic, confirmed COVID-19. After review of the interim safety and efficacy data from 
that clinical trial, the FDA granted on December 18, 2020 an Emergency Use Authorization 
(EUA) for the mRNA-1273 vaccine in adults 18 years of age and older. 

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To potentially enhance and extend the duration of protection provided by the 2-dose vaccination 
schedule of mRNA-1273 administered in the main study, and to gain an understanding of the 
immune responses to a third dose of mRNA-1273, subjects in the main study may participate in 
an optional third mRNA-1273 vaccination substudy, detailed in Section 12, Appendix A. 
Substudy subjects will receive a third mRNA-1273 vaccination, administered via an IM injection 
at a dosage of 100 mcg/0.5 mL, given six to twelve months after receipt of their second 
vaccination in the main study. Substudy subjects will be followed for safety, reactogenicity, and 
immunogenicity endpoints through 12 months post third vaccination (Substudy Day 366). 
To be eligible to participate in the substudy, subjects must have received both the first and 
second mRNA-1273 vaccinations in the main study. Other eligibility criteria are specified in 
Appendix A. Subjects who received only one mRNA-1273 vaccination in the main study will be 
advised to receive an FDA authorized or approved COVID-19 vaccine, according to the 
recommended schedule, when available to them outside of this trial, unless they have a 
contraindication to COVID-19 vaccines that are available. 
Subjects who elect not to participate in the optional third mRNA-1273 vaccination substudy or 
are not eligible for the substudy will continue to be followed according to the Schedule of 
Activities for the main study (see Table 4) with the Final Study Visit 14 occurring at Day 394 
(±14 days). 
Objectives and Endpoints 
Table 2: Objectives and Endpoints (Outcome Measures) 
OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
Primary 
 
• To evaluate the safety and reactogenicity 
of a 2-dose vaccination schedule of 
mRNA-1273, given 28 days apart, across 
5 dosages in healthy adults. 
• Frequency and grade of each solicited 
local and systemic reactogenicity AE 
during a 7-day follow-up period post each 
vaccination. 
• Frequency and grade of any unsolicited 
AEs during the 28-day follow-up period 
post each vaccination. 
• Frequency of any SAEs, Protocol 
Specified AESIs, NOCMCs, and MAAEs 
from Day 1 to Day 394. 
Secondary 
 
• To evaluate the immunogenicity as 
measured by Immunoglobulin G (IgG) 
enzyme-linked immunosorbent assay 
ELISA to the SARS-CoV-2 S (spike) 
protein following a 2-dose vaccination 
schedule of mRNA-1273 at Day 57. 
• Geometric mean titer (GMT) of antibody 
at Day 57. 
• Percentage of subjects who seroconverted, 
defined as a 4-fold change in antibody 
titer from baseline. 

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OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
• The geometric mean fold rise (GMFR) in 
IgG titer from baseline. 
Exploratory 
 
• To evaluate the immunogenicity as 
measured by IgG ELISA to the SARS-
CoV-2 S (spike) protein following a 2-
dose vaccination schedule of mRNA-1273 
at all timepoints, other than Day 57. 
• GMT of antibody at each timepoint. 
• Percentage of subjects who seroconverted 
at each timepoint. 
• The GMFR in IgG titer from baseline at 
each post-vaccination timepoint. 
• To evaluate the immunogenicity as 
measured by Immunoglobulin M (IgM) 
and Immunoglobulin A (IgA) ELISA to 
the SARS-CoV-2 S (spike) protein 
following a 2-dose vaccination schedule of 
mRNA-1273 given 28 days apart. 
• GMT at each timepoint. 
• Percentage of subjects who seroconverted 
at each timepoint. 
• The GMFR in IgM and IgA titer from 
baseline at each post-vaccination 
timepoint. 
• To evaluate the immunogenicity as 
measured by pseudovirus neutralization 
following a 2-dose vaccination schedule of 
mRNA-1273 given 28 days apart. 
• GMT of neutralizing (Neut) antibody at 
each timepoint. 
• Percentage of subjects who seroconverted, 
defined as a 4-fold change in Neut 
antibody titer from baseline at each 
timepoint. 
• The GMFR Neut antibody titer from 
baseline at each post-vaccination 
timepoint. 
• To evaluate the immunogenicity as 
measured by live wild-type SARS-CoV-2 
neutralization following a 2-dose 
vaccination schedule of mRNA-1273 
given 28 days apart. 
• GMT of Neut antibody at each timepoint. 
• Percentage of subjects who seroconverted, 
defined as a 4-fold change in Neut 
antibody titer from baseline at each 
timepoint. 
• The GMFR in Neut antibody titer from 
baseline at each post-vaccination 
timepoint. 

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OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
• To assess, in at least a subset of samples, 
the SARS-CoV-2 S protein-specific T cell 
responses. 
• Magnitude, phenotype, and percentage of 
cytokine producing S protein-specific T 
cells, as measured by flow cytometry at 
different timepoints post vaccination 
relative to baseline. 
Inclusion Criteria (abbreviated) 
See full inclusion criteria in Section 5.1. 
A subject must meet all the following criteria to be eligible to participate in this study: 
1. Provides written informed consent prior to initiation of any study procedures. 
2. Be able to understand and agrees to comply with planned study procedures and be 
available for all study visits. 
3. Agrees to the collection of venous blood per protocol. 
4. Male or non-pregnant female, ≥18 years of age at time of enrollment. 
5. Body mass index (BMI) 18.0-35.0 kg/m2, inclusive (<56 years of age), at screening; BMI 
18.0-30.0 kg/m2, inclusive (≥56 years of age), at screening. 
6. Women of childbearing potential must agree to use or have practiced true abstinence or 
use at least one acceptable primary form of contraception. 
7. In good health. 
8. Oral temperature is less than 100.0°F (37.8°C). 
9. Pulse no greater than 100 beats per minute. 
10. Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive. 
11. Clinical screening laboratory evaluations (White Blood Cells [WBCs], hemoglobin 
[Hgb], platelets [PLTs], Alanine Transaminase [ALT], Aspartate Transaminase [AST], 
Creatinine [Cr], Alkaline Phosphatase [ALP], Total Bilirubin [T. Bili], Lipase, 
Prothrombin Time [PT], Partial Thromboplastin Time [PTT]) are within acceptable 
normal reference ranges at the clinical laboratory being used. 
12. Must agree to have samples stored for secondary research. 
Exclusion Criteria (abbreviated) 
See full exclusion criteria in Section 5.2. 
A subject who meets any of the following criteria will be excluded from participation in this 
study: 
1. Positive pregnancy test either at screening or just prior to each vaccine administration. 
2. Female subject who is breastfeeding or plans to breastfeed from the time of the first 
vaccination through 60 days after the last vaccination. 

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3. Has any medical disease or condition that, in the opinion of the participating site 
Principal Investigator (PI) or appropriate sub-investigator, precludes study participation. 
4. Presence of self-reported or medically documented significant medical or psychiatric 
condition(s). 
5. Has an acute illness, as determined by the participating site PI or appropriate sub-
investigator, with or without fever [oral temperature ≥38.0°C (100.4°F)] within 72 hours 
prior to each vaccination. 
6. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or 
human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening. 
7. Has participated in another investigational study involving any investigational product 
within 60 days, or 5 half-lives, whichever is longer, before the first vaccine 
administration. 
8. Has previously participated in an investigational study involving LNPs (a component of 
the investigational vaccine assessed in this trial). 
9. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, 
generalized urticaria, angioedema, other significant reaction) to any previous licensed or 
unlicensed vaccines. 
10. History of COVID-19 diagnosis. 
11. Reside in a nursing home or other skilled nursing facility or have a requirement for 
skilled nursing care. 
Study Phase 
• 1 
Study Population 
Up to one hundred and fifty-five (155) males and non-pregnant females, ≥18 years of age, who 
are in good health and meet all eligibility criteria will be enrolled. 
Sites 
Up to three domestic clinical research sites 
Study Intervention: 
• mRNA-1273 is an LNP dispersion containing an mRNA that encodes for the pre fusion 
stabilized spike protein SARS-CoV-2. mRNA-1273 consists of an mRNA Drug 
Substance that is manufactured into LNPs composed of the proprietary ionizable lipid, 
SM-102, and 3 commercially available lipids, cholesterol, 1,2-distearoyl-sn-glycero-3-
phosphocholine (DSPC), and PEG2000 DMG. 
• mRNA-1273 (0.5 milligrams [mg]/mL) will be diluted in 0.9% Sodium Chloride (NaCl) 
for injection, United States Pharmacopeia (USP) to obtain 10, 25, 50, 100, and 250 mcg 
in 0.5 mL dosages. Each dose will be administered via IM injection (0.5 mL) into the 
deltoid muscle on Days 1 and 29. The second dose of vaccine (0.5 mL) will be 
administered preferably in the same arm used for the first dose. The pharmacist will 
prepare a single dose (0.5 mL) for each subject based on cohort assignment. 

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Table 3: Dosing and Administration 
Cohort 
Product 
Name 
Dose 
Route 
Frequency of 
Administration 
1 
mRNA-1273 
25 mcg 
IM 
D1, D29 
2 
mRNA-1273 
100 mcg 
IM 
D1, D29 
3 
mRNA-1273 
250 mcg 
IM 
D1, D29 
4 
mRNA-1273 
25 mcg 
IM 
D1, D29 
5 
mRNA-1273 
100 mcg 
IM 
D1, D29 
6* 
mRNA-1273 
250 mcg 
IM 
D1, D29 
7 
mRNA-1273 
25 mcg 
IM 
D1, D29 
8 
mRNA-1273 
100 mcg 
IM 
D1, D29 
9* 
mRNA-1273 
250 mcg 
IM 
D1, D29 
10 
mRNA-1273 
50 mcg 
IM 
D1, D29 
11 
mRNA-1273 
50 mcg 
IM 
D1, D29 
12 
mRNA-1273 
50 mcg 
IM 
D1, D29 
13* 
mRNA-1273 
10 mcg 
IM 
D1, D29 
*Cohorts 6, 9 and 13 were not enrolled. 
Study Duration 
• The duration of the main study is anticipated to be 20 months (from start of screening to 
last subject last visit in the main study). 
• The duration of the optional third mRNA-1273 vaccination substudy is anticipated to be 
12 months from the last subject vaccinated with the third mRNA-1273 vaccination. 
Subject Duration 
• The duration for each individual subject in the main study is approximately 14 months 
(from first contact to last visit in the main study). 
• The duration for each individual subject in the optional third mRNA-1273 vaccination 
substudy is approximately 26 months (from first contact to last visit). 
Safety 
• The study will use a series of halting rules – for sentinel subjects, for the halting of each 
cohort, and for not vaccinating individual subjects. See Section 7.1 for details. 
• This study will use a Safety Monitoring Committee (SMC) for objective oversight of the 
study. SMC reviews are required for study halting. The SMC does not need to meet for 
dose escalation or for initiation of the optional third mRNA-1273 vaccination substudy. 
 
 

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1.2 
Schedule of Activities (SOA) 
Table 4: Schedule of Activities for the Main Study 
Procedures 
Screening 
Visit 00, Day -42 to -1 
Enrollment/Baseline 
Visit 01, Day 1 
Visit 02, Day 2 
1 day post Dose 1 
Visit 03, Day 3 
2 days post Dose 1 
Visit 04 
Day 8 +/- 1 day 
Visit 05 
Day 15 +/- 2 days 
Visit 06 
Day 29 +/- 2 days 
Visit 07, Day 30 
1 day post Dose 2 
Visit 08, Day 31 
2 days post Dose 2 
Visit 09f 
Day 36 +/- 1 day 
Visit 10f 
Day 43 +/- 2 days 
Visit 11f 
Day 57 +/- 2 days 
Visit 11Af 
Day 71 -7/+ 21 days 
Visit 12f 
Day 119 +/- 7 days 
Visit 13f 
Day 209 +/-7 days 
Final Study Visit 14f,g 
Day 394 +/- 14 days 
Unscheduled Visit 
Early Termination 
Visit 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review Eligibility Criteria 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
Vaccination 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Telephone Contact 
 
 
X 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
Interim History 
 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
Physical Examinationa 
X 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
Height and Weight (for BMI) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematologyb 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Chemistryb 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Serologyb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Testc 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug Screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Memory Aid: Solicited AEs 
 
Days 1-8 
 
Days 29-36 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
Days 1-57 
 
 
 
 
 
 
SAEs, Protocol Specified AESIs, MAAEs, 
and NOCMCs 
 
 
Days 1-394 
 
 
Serum for Serological Immunogenicity 
Assays 
 
X 
 
 
 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
 
X 
Peripheral Blood Mononuclear Cells 
(PBMCs) for Cellular Immunology Assays 
 
X 
 
 
 
X 
X 
 
 
X 
X 
X 
 
X 
X 
 
 
X 
Serum for Secondary Researchd 
 
X 
 
 
 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
 
X 
Serum for Product Assay Development 
 
X 
 
 
 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
 
X 
Leukocytes for Secondary Research 
(subset of subjects) 
 
 
 
 
 
 
 
 
 
 
 
 
Xe 
 
 
 
 
 
 

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a) Full physical examination will be performed at screening and symptom-directed (targeted) 
physical examination at all other timepoints if indicated. 
b) Clinical screening laboratory evaluations will include WBCs, Hgb, PLTs, Cr, ALT, AST, 
ALP, T. Bili, Lipase, PT, PTT, hepatitis B surface antigen, hepatitis C virus antibody, and HIV 
types 1 and 2 antigen/antibody. Clinical safety laboratory evaluations obtained on Days 1, 8, 29, 
and 36 will include WBCs, Hgb, PLTs, Cr, ALT, AST, ALP, T. Bili, and Lipase. 
c) For women of childbearing potential serum pregnancy test at screening, and urine or serum 
pregnancy test on Days 1 and 29 with results confirmed as negative prior to enrollment on Day 1 
and administration of each vaccination. 
d) Depending on the timepoint approximately 8 or 16 mL of each venous blood sample is 
designated for secondary research. 
e) For those subjects consented for leukapheresis, screening procedures, including screening 
laboratory evaluations, will be performed locally prior to the leukapheresis procedure. Refer to 
the protocol-specific MOP for details on the leukapheresis procedure. 
f) Visits 09-14 windows should be based off the actual Visit 06 date. 
g) Subjects who participate in the optional third mRNA-1273 vaccination substudy will exit the 
Schedule of Activities for the main study between Visit 13 and the close of the window for Visit 
14 and will not have Visit 14, instead will have Visit 14A and subsequent substudy visits. See 
Section 12, Appendix A for the Schedule of Activities for the optional third mRNA-1273 
vaccination substudy. 
2. 
INTRODUCTION 
2.1 
Background and Study Rationale 
In December 2019 the Wuhan Municipal Health Committee identified an outbreak of viral 
pneumonia cases of unknown cause. Coronavirus RNA was quickly identified in some of these 
patients. This novel Coronavirus (nCoV) was originally referred to as 2019-nCoV but has now 
been named SARS-CoV-2 (due to its similarity to the Severe Acute Respiratory Syndrome 
[SARS] Coronavirus [CoV; SARS-CoV]). It has 89% nucleotide identity with bat SARS-like-
CoVZXC21 and 82% with that of human SARS-CoV (Chan JF et al., 2020). The disease caused 
by SARS-CoV-2 is called Coronavirus disease 2019 (COVID-19). On January 5, 2020 there 
were 59 confirmed cases, 278 cases on January 20, 2118 cases on January 26, rising to more than 
110,000 confirmed cases and 3996 deaths as of March 9, 2020 according to various international 
health reporting agencies. Outbreak forecasting and modeling suggest that these numbers will 
continue to rise (Wu et al., Lancet, Jan. 31, 2020). On January 30, 2020, the International Health 
Regulations Emergency Committee of the World Health Organization (WHO) declared the 
COVID-19 outbreak a Public Health Emergency of International Concern. On January 31, 2020, 
the US Department of Health and Human Services declared a public health emergency in the 
United States. On March 11, 2020 the WHO declared COVID-19 a pandemic. SARS-CoV-2 has 
continued to spread globally with cases being reported in at least 216 countries, and as of May 
14, 2020, 4,307,287 confirmed cases and 295,101 deaths had been reported to the WHO [WHO, 
2020]. 

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Global efforts to evaluate novel antivirals and therapeutic strategies to treat SARS-CoV-2 severe 
infections have intensified, but no proven therapeutic currently exists. There is currently no 
vaccine against the SARS-CoV-2 virus. Therefore, there is an urgent public health need for rapid 
development of novel interventions. Based on currently available information and clinical 
experience suggesting that older adults may be at higher risk for severe illness from COVID-19, 
it is important to rapidly assess clinical safety of novel vaccines in this vulnerable population as 
early as possible. This phase I clinical trial proposes to evaluate safety and immunogenicity of 
Moderna’s mRNA-1273 in healthy adults across the age spectrum (≥18 years of age). To further 
explore dose-ranging, additional cohorts will be enrolled. 
ModernaTX, Inc. has developed a rapid response, proprietary messenger RNA (mRNA)-based 
vaccine platform. This is based on the principle and observations that antigens can be produced 
in vivo by delivery and uptake of the corresponding mRNA by cells. The mRNA then undergoes 
intracellular ribosomal translation to endogenously express the protein antigen(s) encoded by the 
vaccine mRNA. This mRNA-based vaccine does not enter the cellular nucleus or interact with 
the genome, is nonreplicating, and expression is transient. mRNA vaccines thereby offer a 
mechanism to stimulate endogenous production of structurally intact protein antigens in a way 
that mimics wild-type viral infection and are able to induce good immune responses against 
infectious pathogens such as cytomegalovirus (CMV) (NCT03382405), human 
metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) (NCT03392389) and influenza 
virus (NCT03076385 and NCT03345043). ModernaTX, Inc. is using its mRNA-based 
technology to develop a novel LNP-encapsulated messenger RNA (mRNA)-based vaccine 
against SARS-CoV-2. mRNA-1273 is a novel LNP mRNA-based vaccine that encodes for the 
full-length spike (S) protein of SARS-CoV-2, modified to introduce two proline residues to 
stabilize the S protein into a pre-fusogenic form. 
The coronavirus spike (S) protein mediates attachment and entry of the virus into host cells, 
making it a primary target for neutralizing antibodies that prevent infection (Johnson et al. 2016; 
Wang et al. 2016; Wang et al. 2015; Wang et al. 2018; Chen et al. 2017; Corti et al. 2015; Yu et 
al. 2015; Kim et al. 2019; Widjaja et al. 2019). The Vaccine Research Center (VRC) and 
collaborators have identified 2 proline mutations at the apex of the S2 central helix that stabilize 
the S protein in its prefusion conformation (S-2P) (Pallesen et al. 2017). These mutations have 
been applied to 9 diverse coronaviruses from three coronavirus genera and found to stabilize the 
prefusion conformation and improve protein expression. Since this mutation has consistently 
stabilized other beta-CoV S proteins, this mutation was applied to the SARS-CoV-2 S protein. 
The VRC and collaborators found that the stabilized SARS-CoV-2 S-2P expressed well and is in 
the prefusion conformation based on negative-stain electron microscopy. 
The S proteins of closely related beta-CoVs stabilized by the 2P mutation, including HKU1, 
Middle East Respiratory Syndrome (MERS), SARS, and WIV1, are potent immunogens in mice. 
In collaboration with ModernaTX, Inc, mRNA expressing the MERS S-2P protein sequence was 
produced and compared to mRNA expressing wild-type S protein. mRNA expressing the MERS 
S-2P protein was more immunogenic than mRNA expressing wild-type S protein, and mice 
immunized with a dose as low as 0.016 mcg of MERS S-2P mRNA had neutralizing activity 
above the threshold of protection in dipeptidyl peptidase 4 (hDPP4) mice and protected mice 
from MERS challenge. Based on the robust immunogenicity of the MERS S-2P mRNA vaccine 
in mice, the VRC and ModernaTX, Inc. designed mRNA expressing a membrane-anchored 

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SARS-CoV-2 S protein stabilized with the 2P mutation. HEK293 cells transfected with mRNA 
expressing the SARS-CoV-2 S-2P protein successfully expressed the protein. 
mRNA-1273 is immunogenic in BALB/c mice, demonstrating a dose-dependent antibody 
response as measured in both SARS-CoV-2 S protein binding and virus neutralizing antibody 
assays. A strong correlation was measured between S protein binding antibody and virus 
neutralization. In addition, a single dose of mRNA-1273 elicited robust S protein binding 
antibody titers, but with no virus neutralization titers observed. Mice from this study were 
challenged with mouse-adapted SARS-CoV-2 virus, and preliminary results indicate that 
mRNA-1273-induced immunity is protective after challenge. Mice immunized with a single dose 
of 10 or 1 mcg of mRNA-1273 were protected from viral replication in the lung following 
challenge 7 weeks after vaccination, despite the absence of measurable neutralization titers. Mice 
immunized with 2 doses of either 1 or 0.1 mcg of mRNA-1273 were also protected, dependent 
upon the dosing schedule. 
There is some clinical experience with vaccines targeting coronavirus S proteins. The first 
candidate DNA vaccine expressing SARS S protein was evaluated in 10 healthy adults age 21 to 
49 years in 2004 and 2005 following a rapid vaccine development response to the SARS 
outbreak (Martin et al. 2008). DNA vaccine at a dosage of 4 mg was administered IM by a 
Biojector needle free device at baseline, week 4 and week 8. The vaccine was safe and well 
tolerated. Local and systemic reactogenicity events were mild and transient. There were no SAEs 
and no grade 3 or 4 AEs. The SARS candidate vaccine was immunogenic as assessed by ELISA 
and pseudotyped lentiviral vector reporter neutralization assay following the first injection in 
most subjects with peak response after the 3rd vaccination. Vaccine induced T cell responses as 
assessed by ICS and ELISPOT were detected in all subjects (Martin et al. 2008). 
Additionally, a candidate DNA vaccine expressing MERS S was evaluated in 75 healthy subjects 
ages 19 to 50 years in 2016 (Modjarrad et al. 2019). In a dose escalation trial, DNA vaccine at a 
dosage of 0.67 mg, 2 mg or 6 mg was administered IM followed by electroporation at baseline, 
week 4 and week 12. Overall, the vaccine was safe and well tolerated. Local and systemic 
reactogenicity events were generally mild and transient. There were no SAEs or grade 3 or 4 
laboratory abnormalities attributed to vaccination. The MERS candidate vaccine was 
immunogenic as assessed by seroconversion and vaccine induced T cell responses in most 
vaccine recipients. (Modjarrad et al. 2019). 

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The expression of functional prefusion stabilized S-protein delivered by mRNA was evaluated in 
HEK293 cells (Figure 1).
 
Figure 1. The SARS-CoV-2 full-length stabilized spike protein (S-2P) delivered by mRNA is 
expressed on the cell surface. HEK293T cells were transfected with mRNA encoding for the 
SARS-CoV-2 S-2P protein. After 24hrs, cell flow cytometry was used to measure surface 
expression by staining with (A) mouse polyclonal antibody raised against SARS S-2P protein; 
(B) a flag-tagged ace2 receptor and anti-flag antibody; (C) a SARS S-protein monoclonal 
antibody (mAb-103) that cross-reacts with SARS-CoV-2 S-2P; (D) a SARS S protein-specific 
monoclonal antibody (mAb 16) that does not bind SARS-CoV-2 was used as a negative control. 
The expressed prefusion, stabilized S protein binds to the its proposed receptor, human ACE-2, 
and is recognized by cross reactive antibodies to SARS S protein. It is therefore anticipated that 
mRNA-1273 will generate robust immune responses to the SARS-CoV-2 S protein. 
2.1.1 
Public Readiness and Emergency Preparedness Act 
The study vaccine, mRNA-1273, and the efforts for this clinical trial are covered under the 
Public Readiness and Emergency Preparedness Act (PREP Act) and the Declaration issued by 
the Secretary of the U.S. Department of Health and Human Services under that Act. Under the 
PREP Act and the Declaration, covered persons (such as manufacturers, distributers, program 
planners, and other qualified persons who prescribe, administer or dispense study product) are 
immune from liability from the administration, or use of a covered countermeasure, such as 
mRNA-1273. The PREP Act provides immunity for covered persons from liability, unless the 
injury was caused by willful misconduct. The Declaration invoking the PREP Act for COVID-19 
covered countermeasures was made on March 10, 2020 and is retroactively effective from 
February 4, 2020. 
The PREP Act also established the Countermeasures Injury Compensation Program (CICP) to 
provide compensation for serious injuries or death that occur as the direct result of the 
administration or use of certain countermeasures. Any requests for compensation must be filed 
within one year of the administration or use of the covered countermeasure. Requests for 
Benefits must be made to the Health Resources and Services Administration’s (HRSA) 
Countermeasures Injury Compensation Program (http://www.hrsa.gov/cicp/) by filing a Request 
for Benefits Form and all required medical records and supporting documentation. Additional 
information on filing a Request for Benefits is available on the CICP’s website at 
http://www.hrsa.gov/cicp/. Compensation may then be available for reasonable and necessary 

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medical benefits, lost wages and/or death benefits to eligible individuals for certain injuries in 
accordance with regulations published by the Secretary of HHS (found at 42 CFR part 110). 
If an individual suffers a serious physical injury or death from the administration or use of a 
covered countermeasure in this study, the individual, the individual’s legal or personal 
representative, the administrator/executor of a deceased individual’s estate, or certain survivors 
may request benefits from the CICP. A serious physical injury means an injury that warranted 
hospitalization (whether or not the person was actually hospitalized) or that led to a significant 
loss of function or disability. The CICP is the payer of last resort. This means that it only covers 
expenses or provides benefits that other third-party payers (such as health insurance, the 
Department of Veterans Affairs, or Workers’ Compensation programs) do not have an obligation 
to pay. 
If the Secretary of HHS does not make a final determination on the individual’s request within 
240 days, or if the individual decides not to accept the compensation, the injured individual or 
his representative may pursue a tort claim in the US District Court for the District of Columbia, 
but only if the claim involves willful misconduct and meets the other requirements for suit under 
the PREP Act. Any award is reduced by any public or private insurance or worker’s 
compensation available to the injured individual. Awards for non-economic damages, such as 
pain, suffering, physical impairment, mental anguish, and loss of consortium are also limited. If 
the individual accepts compensation, or if there is no willful misconduct, then the individual does 
not have a tort claim that can be filed in a US Federal or a State court. 
2.2 
Risk/Benefit Assessment 
2.2.1 
Known Potential Risks 
The potential risks of participating in this trial are those associated with having blood drawn, IM 
injection, leukapheresis (only for those subjects consented for leukapheresis), possible reactions 
to mRNA-1273, and breach of confidentiality. 
Drawing blood may cause transient discomfort and fainting. Fainting is usually transient and 
managed by having the subject lie down and elevate his/her legs. Bruising at the blood draw site 
may occur but can be prevented or lessened by applying pressure to the blood draw site for a few 
minutes after the blood is taken. IM injection may also cause transient discomfort and fainting. 
Drawing blood and IM injection may cause infection. The use of aseptic (sterile) technique will 
make infection at the site where blood will be drawn or where the vaccination will be given 
extremely unlikely. 
Risks of Leukapheresis (only for those subjects consented for leukapheresis) 
Leukapheresis may be associated with pain, bruising, and discomfort in the arms at the site of 
needle placement. Vasovagal episodes, characterized by transient hypotension, dizziness, nausea, 
and rarely syncope, are seen in less than 5% of procedures. Additional risks include increased 
pulse, seizures, and blood loss. Anticoagulants added to prevent the blood from clotting may lead 
to a sour taste in the mouth, mild muscle cramps and/or tingling sensation around the mouth, feet 
or hands. These reactions may be seen to a mild degree in 30-50% of leukapheresis procedures 
and can usually be relieved by slowing or temporarily interrupting the procedure or 
administering calcium carbonate tablets. 

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A temporary decrease (1-2 days) in red blood cell count is common. Rarely, machine 
malfunction or if the procedure needs to be stopped before completion may result in the loss of a 
half pint to a pint of blood. Leukapheresis does not affect the blood’s ability to form clots in the 
event of subsequent cuts or injuries. 
There may be additional risks that are unknown at this time. 
Preclinical evaluations will occur in parallel with this phase I clinical trial. However, in support 
of the development of mRNA-1273 for prophylaxis against SARS-CoV-2 infection, nonclinical 
immunogenicity, a Good Laboratory Practice (GLP)-compliant, repeat dose toxicology study, as 
well as biodistribution and genotoxicity studies have been completed with similar mRNA-based 
vaccines formulated in SM-102-containing LNPs. 
Risks of mRNA-1273 
In preclinical models, the aggregate toxicity profile observed across multiple repeat-dose 
toxicology studies at IM doses ranging from 9 to 150 mcg/dose administered once every 2 weeks 
for up to 6 weeks is generally consistent and considered as being representative of mRNA 
vaccines formulated in the same SM-102 LNP formulation, differing only by the encapsulated 
mRNA sequence(s). All doses administered were tolerated and the lowest no-observed-adverse-
effect-level (NOAEL) determined across the aggregate of the completed studies was 89 
mcg/dose. 
In a non-GLP biodistribution study with mRNA-1647, a similar mRNA-based vaccine 
formulated in SM-102-containing LNPs, only a relatively small fraction of the administered 
mRNA-1647 dose distributed to distant tissues, and the mRNA constructs did not persist past 1 
to 3 days in tissues other than the injection site, lymph nodes, and spleen in male Sprague 
Dawley rats. 
In GLP-compliant studies, SM-102, the novel lipid component of the LNP formulation, was not 
genotoxic when tested in a bacterial reverse mutation (Ames) test or an in vitro micronucleus 
test. An in vivo micronucleus study in Sprague Dawley rats showed that a similar mRNA-based 
vaccine formulated in SM-102-containing LNPs (mRNA-1706, which encodes the ZIKV pre-
membrane and envelope polypeptide [different from the sequence encoded in mRNA-1893]), 
induced statistically significant increases in micronucleated immature erythrocytes in male rats at 
both 24 and 48 hours and in female rats at 48 hours only; however, there was no clear dose 
response, and the increases were generally weak and associated with minimal bone marrow 
toxicity. These observations indicate that the risk to humans after IM administration is low due to 
minimal systemic exposure. 
In a non-GLP study in Sprague Dawley rats to characterize the potential toxicity of mRNA-1273 
at clinically relevant doses, mRNA-1273 exhibited clinical signs consisting of transient dose-
dependent injection site edema with or without hindlimb impairment at approximately 24 hours 
post-dose that generally resolved within 7 days after dose administration. mRNA-1273-related 
clinical pathology changes associated with inflammation, including increased neutrophils, 
eosinophils, and/or globulin, were observed as well as other mild mRNA-1273-related changes 
including decreased red cell mass, reticulocytes, and lymphocytes and increased creatinine, 
triglyceride, cholesterol, and/or glucose. There were no mRNA-1273-related effects on body 
weight. In general, these changes are consistent with the results from previous GLP rat toxicity 
studies conducted with other mRNAs formulated in SM-102 LNP. 

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Information on possible risks and adverse reactions associated with IM administration of mRNA-
1273 is derived from animal studies with mRNA-1273, interim safety information from this 
ongoing phase I clinical trial of mRNA-1273 (NCT04283461), interim findings from the Phase 3 
placebo-controlled clinical trial of mRNA-1273 (NCT04470427, the COVE study), and the LNP 
components or animal and human studies of similar mRNA-based vaccines (mRNA-1647 and 
mRNA-1653). 
As of March 2020, there had been 8 non-SARS-CoV-2 clinical studies initiated across 
Moderna’s infectious disease vaccine platform with over 1,000 subjects receiving at least one 
dose of an mRNA vaccine. mRNA vaccines with SM-102-containing lipid formulations are 
currently being evaluated in 3 indications: prophylactic protection against human CMV 
(NCT03382405), hMPV/PIV3 (NCT03392389), and Zika virus (NCT04064905). In three Phase 
1 studies as of January 6, 2020, approximately 365 subjects were dosed with either an SM-102-
containing lipid vaccine or placebo (doses ranging from 10 mcg to 300 mcg). Of the 365 subjects 
dosed 264 subjects experienced at least 1 solicited AE. The most common solicited events were 
pain 28% of total events reported, headache 15%, fatigue 15%, myalgia 13%, arthralgia 9%, 
nausea 7%, chills 6%, fever, 4%, erythema, 2%, and swelling 2%. The majority of the events 
were grade 1-2 with approximately 9% being reported as grade 3; the most common grade 3 
events were pain, myalgia, fatigue, headache, and chills. Grade 3 events were typically recorded 
on Day 1 or Day 2 following injection with most occurring on Day 2 and resolving by Day 6. 
In an hMPV/PIV3 Phase 1 study, which is unblinded, unsolicited related AEs included mild to 
moderate chills, hot flushes, diarrhea, pyrexia, temperature intolerance, elevated WBC count, 
headache and erythematous rash, as well as severe injection site pain, prolonged PT and myalgia. 
All of the severe events occurred at the 300 mcg x 2 dose level. In the blinded Phase 1 CMV 
study, unsolicited related AEs in more than 2 subjects included chills (19 subjects, or 10.5%); 
fatigue (10 subjects, 5.5%);, lymphadenopathy, injection site pain, and pyrexia, (9 subjects each, 
5.0%); arthralgia (8 subjects, 4.4%); myalgia (7 subjects, 3.9%); headache (5 subjects, 2.8%);, 
diarrhea (4 subjects, 2.2%); and injection site bruising ( 3 subjects, 1.7%). Of these AEs, severe 
events were reported in 3 of 19 subjects with chills, 5 of 10 subjects with fatigue, 4 of 9 subjects 
with pyrexia, 4 of 8 subjects with arthralgia, and 4 of 7 subjects with myalgia. There were no 
related SAEs reported in the Phase 1 CMV, hMPV/PIV3 or Zika virus vaccine studies. 
In addition, other AEs that have been generally associated with approved IM administered 
vaccines have included mild hematological and clinical chemistry abnormalities, which are 
usually reversible. 
To date, interim safety data from this phase I clinical trial of mRNA-1273 indicate that solicited 
adverse reactions within 7 days after the first or second vaccination were reported by over 90% 
of the 120 subjects (Jackson, LA, et al. 2020; Anderson, EJ, et al, 2020). Most were mild or 
moderate in severity. Moderate or severe solicited adverse reactions were reported more 
commonly after the second vaccination compared with the first and with higher dosages. Severe 
solicited systemic adverse reactions were reported in 6 (5%) of subjects. Evaluation of safety 
clinical laboratory values of grade 2 or higher and unsolicited adverse events revealed no 
patterns of concern. No deaths or SAEs related to mRNA-1273 have been reported in this trial 
and no prespecified halting rules for vaccination were met. Three study subjects discontinued 
due to an AE. One subject in the 25 mcg vaccination group (age stratum: 18 to 55 years) reported 
mild urticaria (hives on lower extremities) on Day 5 after Dose 1. The event was deemed related 

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to mRNA-1273 by the investigator. One subject in the 250 mcg vaccination group (age stratum: 
18 to 55 years) reported mild oropharyngeal pain (sore throat) on Day 24 after Dose 1 and one 
subject in the 100 mcg vaccination group (age stratum: 56 to 70 years) reported moderate 
maculopapular rash on Day 9 after Dose 1. These two events were deemed not related to mRNA-
1273 by the investigator. 
Participants 18 years of age and older received a 2-dose regimen (0, 28 days) of mRNA-1273 in 
the Phase 3 placebo-controlled clinical trial (COVE) conducted in the United States, and were 
followed for the development of COVID-19 disease. Interim findings indicated that vaccine 
recipients had higher rates of local reactions (e.g., pain, erythema, swelling) and systemic 
reactions (e.g., headache, fatigue, myalgia) than placebo recipients and that most reactions were 
mild to moderate and resolved over 1-3 days (Baden LR, et al. 2020). The severity of the 
solicited systemic events increased after the second dose of mRNA-1273, with an increase in 
events of moderate severity of from 16.5% after the first dose to 38.1% after the second dose, 
and with an increase in events graded as severe of from 2.9% after the first dose to 15.8% after 
the second dose. Both solicited injection-site and systemic adverse events were more common 
among younger subjects (18 to <65 years of age) than among older subjects (≥65 years of age). 
The frequency of severe unsolicited events was similar in the placebo (1.3%) and vaccine (1.5%) 
groups, as were the frequencies of medically attended adverse events (9.7% vs. 9.0%) and 
serious adverse events (0.6% in both groups). Three deaths occurred in the placebo group (one 
from intraabdominal perforation, one from cardiopulmonary arrest, and 1 from severe systemic 
inflammatory syndrome in a subject with chronic lymphocytic leukemia and diffuse bullous 
rash) and 2 in the vaccine group (one from cardiopulmonary arrest and one by suicide). Bell’s 
palsy occurred in the vaccine group (3 subjects [<0.1%]) and the placebo group (1 subject 
[<0.1%]) during the observation period of the trial (more than 28 days after injection). 
Hypersensitivity reactions occurred in 1.5% and 1.1% of subjects in the vaccine and placebo 
groups, respectively. 
Following the issuance of the Emergency Use Authorization (EUA), rare anaphylactic-like 
reactions have occurred among recipients of both mRNA COVID-19 vaccines (Pfizer-BioNTech 
and Moderna). As of January 22, 2021, 10 cases of anaphylaxis, with no associated deaths, have 
been reported in patients who received mRNA-1273 under EUA (CDC COVID-19 Response 
Team; Food and Drug Administration, 2021). Based on the clinical experience to date with 
mRNA-based vaccines, mRNA-1273 should not be administered to individuals with a known 
hypersensitivity to any component of the study product, including polyethylene glycol (PEG). 
Recently, myocarditis and pericarditis have been reported rarely following vaccination with the 
Moderna COVID-19 EUA Vaccine. Although causality has not been established, the majority of 
cases have been in young males (<30 years old), occurring a few days to up to a week after the 
vaccination and seen more commonly after the second dose. However, cases have been reported 
in older males, females, as well as after the first dose of vaccine. Most cases are generally mild, 
and individuals tend to recover within a short time after treatment. However, long term outcomes 
are unknown. Additionally, it is not known whether the risks of myocarditis or pericarditis are 
increased following additional doses of vaccine. 
Subjects will be informed of the potential risk of myocarditis or pericarditis and be advised to 
monitor for symptoms of myocarditis or pericarditis, including chest pain, shortness of breath, 

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tachycardia, or palpitations. Subjects will be encouraged to immediately contact research staff 
and their medical providers if these symptoms occur following a study vaccination. 
Several animal studies with experimental whole-virus inactivated and subunit vaccines of other 
coronaviruses have shown enhanced immunopathology in a greater number of vaccinated 
animals compared to controls upon subsequent virus infection. These experimental vaccines 
often exhibited Th2-biased immune responses or elicited antibodies that had poor neutralizing 
activity against the virus. In mice vaccinated with two doses of mRNA-1273, a balanced 
antibody response resulting in high titers of both IgG1 and IgG2a was observed. A predominant 
Th2-focused immune response with only IgG1 responses was not observed. Data from mice and 
non-human primates have not identified risk with mRNA-1273 (Corbett KS et al, N Engl J Med 
2020; Corbett KS et al, Nature 2020). 
Most people during their lifetimes have likely been infected with one or more of the 4 endemic 
strains of human coronaviruses (hCoV 229E, NL63, OC43, and HKU1) that circulate globally 
and are responsible for 10-30% of mild to moderate upper respiratory tract infections. Despite 
the likelihood of cross-reactive antibody responses with poor functional activity, no evidence of 
enhanced CoV disease in humans has ever been reported. 
Interim immunogenicity data from this phase I clinical trial of mRNA-1273 have indicated that 
vaccination induced type 1 helper T cell (Th1)–biased CD4+ T cell responses and low or 
undetectable Th2 or CD8+ T cell responses (Jackson LA et al, 2020; Anderson EJ et al, 2020). 
Additionally, no enhancement of respiratory disease has occurred in recipients of mRNA 
vaccines that had breakthrough SARS-CoV-2 infections (Baden LR et al, 2020; Polack FP et al, 
2020). Importantly, of the 30 protocol-defined severe cases of COVID-19 that occurred in the 
Phase 3 placebo-controlled clinical trial of mRNA-1273 (COVE), all 30 occurred in the placebo 
group (Baden LR et al, 2020). Thus, to date, enhanced SARS-CoV-2 respiratory disease has not 
been observed after mRNA-1273 administration. 
Risks to Privacy 
Subjects will be asked to provide personal health information (PHI). All attempts will be made to 
keep this PHI confidential within the limits of the law. However, there is a chance that 
unauthorized persons will see the subject’s PHI. All study records will be kept in a locked file 
cabinet or maintained in a locked room at the participating site. Electronic files will be password 
protected. Only people who are involved in the conduct, oversight, monitoring, or auditing of 
this trial will be allowed access to the PHI that is collected. Any publications from this trial will 
not use information that will identify subjects by name. Organizations that may inspect and/or 
copy research records maintained at the participating site for quality assurance (QA) and data 
analysis include groups such as the IRB, NIAID and the FDA. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by US Law. This web site will not include information that can identify subjects. 
There may be other risks, discomforts or side effects that are unknown at this time. 
Risks of Genetic Testing 
Any genetic data generated will be kept private. There may be a risk that information resulting 
from research genetic testing could be misused for discriminatory purposes. However, state and 

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federal laws provide protections against genetic discrimination. Researchers will need to 
maintain confidentiality in order to be granted access to genetic information. 
2.2.2 
Known Potential Benefits 
There is no direct benefit to the subjects. There is potential benefit to society resulting from 
insights gained from participation in this study due to the emerging threat of the SARS-CoV-2 
outbreak. Vaccination using mRNA-1273 may or may not provide protection against infection 
by SARS-CoV-2. The duration of any such protection is currently unknown. 
As outlined in Section 12.2, data from the Phase 3 placebo-controlled clinical trial of mRNA-
1273 (COVE) suggests 94.1% efficacy of the vaccine when administered at 100 mcg versus 
placebo against SARS-CoV-2 infection when assessed on November 25, 2020 (Baden LR et al, 
2020). The efficacy of other doses of mRNA-1273 (e.g., 25, 50, or 250 mcg) is not known. 
Although declines in binding and neutralizing antibodies are observed over time, 100 mcg of 
mRNA-1273 has the potential to provide durable humoral immunity (Widge AT et al, 2020). 
3. 
OBJECTIVES AND ENDPOINTS 
Table 5: Objectives and Endpoints (Outcome Measures) 
OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
Primary 
 
• 
To evaluate the safety and reactogenicity 
of a 2-dose vaccination schedule of 
mRNA-1273, given 28 days apart, across 
5 dosages in healthy adults. 
• 
Frequency and grade of each solicited 
local and systemic reactogenicity AE 
during a 7-day follow-up period post each 
vaccination. 
• 
Frequency and grade of any unsolicited 
AEs during the 28-day follow-up period 
post each vaccination. 
• 
Frequency of any SAEs, Protocol 
Specified AESIs, NOCMCs, and MAAEs 
from Day 1 to Day 394. 
Secondary 
 
• 
To evaluate the immunogenicity as 
measured by IgG ELISA to the SARS-
CoV-2 S (spike) protein following a 2-
dose vaccination schedule of mRNA-1273 
at Day 57. 
• 
GMT of antibody at Day 57. 
• 
Percentage of subjects who seroconverted, 
defined as a 4-fold change in antibody 
titer from baseline. 
• 
The GMFR in IgG titer from baseline. 
Exploratory 
 

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OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
• 
To evaluate the immunogenicity as 
measured by IgG ELISA to the SARS-
CoV-2 S (spike) protein following a 2-
dose vaccination schedule of mRNA-1273 
at all timepoints, other than Day 57. 
• 
GMT of antibody at each timepoint. 
• 
Percentage of subjects who seroconverted 
at each timepoint. 
• 
The GMFR in IgG titer from baseline at 
each post-vaccination timepoint. 
• 
To evaluate the immunogenicity as 
measured by IgM and IgA ELISA to the 
SARS-CoV-2 S (spike) protein following 
a 2-dose vaccination schedule of mRNA-
1273 given 28 days apart. 
• 
GMT at each timepoint. 
• 
Percentage of subjects who seroconverted 
at each timepoint. 
• 
The GMFR in IgM and IgA titer from 
baseline at each post-vaccination 
timepoint. 
• 
To evaluate the immunogenicity as 
measured by pseudovirus neutralization 
following a 2-dose vaccination schedule 
of mRNA-1273 given 28 days apart. 
• 
GMT of Neut antibody at each timepoint. 
• 
Percentage of subjects who seroconverted, 
defined as a 4-fold change in Neut 
antibody titer from baseline at each 
timepoint. 
• 
The GMFR Neut antibody titer from 
baseline at each post-vaccination 
timepoint. 
• 
To evaluate the immunogenicity as 
measured by live wild-type SARS-CoV-2 
neutralization following a 2-dose 
vaccination schedule of mRNA-1273 
given 28 days apart. 
• 
GMT of Neut antibody at each timepoint. 
• 
Percentage of subjects who seroconverted, 
defined as a 4-fold change in Neut 
antibody titer from baseline at each 
timepoint. 
• 
The GMFR in Neut antibody titer from 
baseline at each post-vaccination 
timepoint. 
• 
To assess, in at least a subset of samples, 
the SARS-CoV-2 S protein-specific T cell 
responses. 
• 
Magnitude, phenotype, and percentage of 
cytokine producing S protein-specific T 
cells, as measured by flow cytometry at 
different timepoints post vaccination 
relative to baseline. 

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4. 
STUDY DESIGN 
4.1 
Overall Design 
This is a phase I, open-label, dose-ranging clinical trial in males and non-pregnant females, ≥18 
years of age, who are in good health and meet all eligibility criteria. This clinical trial is designed 
to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by 
ModernaTX, Inc. mRNA-1273 is a novel LNP-encapsulated mRNA-based vaccine that encodes 
for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at 
up to three domestic clinical research sites. 
Table 6: Treatment Arms 
Cohort 
Sample Size 
Stratum 
(Years of Age) 
First and Second Dose 
1 
15 
18-55 
25 mcg mRNA-1273 
2 
15 
18-55 
100 mcg mRNA-1273 
3 
15 
18-55 
250 mcg mRNA-1273 
4 
10 
56-70 
25 mcg mRNA-1273 
5 
10 
56-70 
100 mcg mRNA-1273 
6* 
10 
56-70 
250 mcg mRNA-1273 
7 
10 
≥71 
25 mcg mRNA-1273 
8 
10 
≥71 
100 mcg mRNA-1273 
9* 
10 
≥71 
250 mcg mRNA-1273 
10 
15 
18-55 
50 mcg mRNA-1273 
11 
10 
56-70 
50 mcg mRNA-1273 
12 
10 
≥71 
50 mcg mRNA-1273 
13* 
15 
18-55 
10 mcg mRNA-1273 
*Cohorts 6, 9 and 13 were not enrolled. 
Up to one hundred and fifty-five (155) subjects will be enrolled into one of thirteen cohorts (10 
mcg, 25 mcg, 50 mcg, 100 mcg, or 250 mcg). Subjects will receive an IM injection (0.5 mL) of 
mRNA-1273 on Days 1 and 29 in the deltoid muscle and will be followed through 12 months 
post second vaccination (Day 394). The second dose of vaccine (0.5 mL) will be administered 
preferably in the same arm used for the first dose. 

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Follow-up visits will occur 1, 2 and 4 weeks post each vaccination (Days 8, 15, 29, 36, 43, and 
57), as well as 3, 6 and 12 months post second vaccination (Days 119, 209 and 394). 
Reactogenicity will be assessed at these visits, as well as blood will be drawn for 
immunogenicity assays. Additional safety and reactogenicity data will be solicited via telephone 
calls to subjects 1 and 2 days post each vaccination (Days 2, 3, 30, and 31). 
To determine early safety signals for this phase I clinical trial, vaccination will proceed in a 
staged fashion. Sentinel subject dosing will begin with 4 subjects in cohort 1 (25 mcg). The 4 
sentinel subjects for cohort 2 (100 mcg) will be enrolled no earlier than one day after enrollment 
of the last of the 4 sentinel subjects in cohort 1. If no halting rules have been met after the 8 
sentinel subjects have completed Day 5, then full enrollment will proceed first with the 
remaining subjects in cohort 1, followed by the remaining subjects in cohort 2 without 
interruption. If no halting rules have been met after all subjects in cohort 2 have completed Day 
8, then dosing of 4 sentinel subjects will begin in cohort 3. If no halting rules have been met after 
the 4 sentinel subjects in cohort 3 have completed Day 5, then full enrollment of cohort 3 will 
proceed. 
If no halting rules have been met after all subjects in cohorts 1 and 2 have completed Day 8, 
dosing will begin for cohorts 4 (25 mcg; 56-70 years of age) and 5 (100 mcg; 56-70 years of 
age). If no halting rules have been met after all subjects in cohorts 4 and 5 have completed Day 
8, dosing will begin for cohorts 7 (25 mcg; ≥71 years of age) and 8 (100 mcg; ≥71 years of age). 
Based on the interim immunogenicity data available as of May 15, 2020, enrollment into cohorts 
6 and 9 (250 mcg; 56-70 years of age and ≥71 years of age) will be deferred in order to explore 
lower dosages. Therefore, enrollment of cohorts 10-12 (50 mcg; 18-55 years of age, 56-70 years 
of age and ≥71 years of age) will be prioritized. Subjects will be enrolled simultaneously in 
cohorts 10-12; there will be no staging. To further explore dosage sparing, cohort 13 (10 mcg 
dose; 18-55 years of age) may be enrolled. A decision regarding the enrollment of cohorts 6, 9 
and 13 will be made after review of interim immunogenicity data from cohorts 1-5, 7, 8, and 10-
12. 
If no halting rules have been met after all subjects in cohorts 5 and 8 have completed Day 8, 
dosing will begin concurrently for cohorts 10-12. If no halting rules have been met after all 
subjects in cohorts 3, 7 and 8 have completed Day 8, dosing may begin for cohort 6, if enrolled. 
If no halting rules have been met after all subjects in cohort 6 have completed Day 8, dosing may 
begin for cohort 9, if enrolled. 
For public health reasons the following early data reviews by the study team are anticipated: 
• Sentinel subjects in cohorts 1 and 2, ELISA IgG data through Day 29; 
• All subjects in cohorts 1 and 2, ELISA IgG data through Day 29; 
• Sentinel subjects in cohort 3, ELISA IgG data through Day 29; 
• All subjects in cohort 3, ELISA IgG data through Day 29; 
• All subjects in cohorts 4, 5, 7 and 8, ELISA IgG data through Day 29; 
• All subjects in cohorts 10-12, ELISA IgG data through Day 29; 
• All subjects in cohort 13, ELISA IgG data through Day 29 (if cohort is enrolled); 

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• All subjects in cohorts 6 and 9, ELISA IgG data through Day 29 (if cohorts are enrolled); 
• Sentinel subjects in cohorts 1 and 2, ELISA IgG data through Day 57; 
• All subjects in cohorts 1 and 2, ELISA IgG data through Day 57; 
• Sentinel subjects in cohort 3, ELISA IgG data through Day 57; 
• All subjects in cohort 3, ELISA IgG data through Day 57; 
• All subjects in cohorts 4, 5, 7 and 8, ELISA IgG data through Day 57; 
• All subjects in cohorts 10-12, ELISA IgG data through Day 57; 
• All subjects in cohort 13, ELISA IgG data through Day 57 (if cohort is enrolled) 
• All subjects in cohorts 6 and 9, ELISA IgG data through Day 57 (if cohorts are enrolled). 
• Additional data review of immunogenicity may be performed to inform public health 
decisions. 
• AEs and SAEs by cohort can be reviewed as necessary. 
• After Day 57 of the last subject in cohort 3, all available data can be reviewed when 
applicable. 
• After Day 57 of the last subject in cohort 8, all available data can be reviewed when 
applicable. 
• After Day 57 of the last subject in cohort 12, all available data can be reviewed when 
applicable. 
• After Day 57 of the last subject in cohorts 6 and 9 (if cohorts are enrolled), all available 
data can be reviewed when applicable. 
• After Day 57 of the last subject in cohort 13 (if cohort is enrolled), all available data can 
be reviewed when applicable. 
Data may be disseminated to public health officials and partners as needed and included in 
publications and presentations to inform the global scientific community. 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of each vaccination through 7 days post each vaccination. Unsolicited 
non-serious AEs will be collected from the time of each vaccination through 28 days post each 
vaccination. SAEs, Protocol Specified AESIs, NOCMCs, and MAAEs, will be collected through 
12 months after the second vaccination (Day 394). 
Clinical safety laboratory evaluations will be performed at screening, as well as immediately 
prior to and 7 days post each vaccination (Days 1, 8, 29, and 36). 
Evaluation of immunogenicity will include quantitation of antibodies to the SARS-CoV-2 S 
protein at multiple timepoints post vaccination as measured by ELISA, pseudovirus and live 
wild-type virus neutralization assays. In addition, exploratory studies to characterize T cell 
responses are planned. Venous blood will also be collected at multiple timepoints post 
vaccination for the secondary research use of serum, plasma and PBMCs. 

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To support development of diagnostics, therapeutics and vaccines, a subset of subjects enrolled 
in cohorts 2, 3, 5, 10, and 11 may undergo leukapheresis to collect additional samples for 
secondary research. If enrollment in cohort 6 proceeds, a subset of subjects in this cohort may 
also undergo leukapheresis. 
Based on interim immunogenicity and reactogenicity data, Cohorts 6, 9 and 13 were not 
enrolled. 
After the IND is in effect, IRB review and approval, and site activation, the participating site will 
begin recruitment outreach efforts, which can include fliers, letters, telephone calls, etc. 
Information regarding this trial may be provided to potential subjects who have previously 
participated in other vaccine trials conducted at the participating site. Other forms and/or 
mechanisms of recruitment may also be used. The IRB will approve the recruitment process and 
all materials prior to use. Screening can occur up to 42 days prior to the first dose. 
Schedule of assessments are found in Section 1.2, Schedule of Activities for the Main Study. 
Dose escalation or dose-ranging details are found in Section 6.1.2, Dosing and Administration. 
Full details of the interim analysis are found in Section 9.4.6, Planned Interim and Early 
Analyses. 
4.2 
Scientific Rationale for Study Design 
This phase I clinical trial is designed as an open-label study, without a placebo arm. Given the 
small sample size, the use of a placebo group is unlikely to improve understanding of AEs. 
Additionally, having the study unblinded will facilitate the need for rapid review and 
dissemination of study data for public health reasons. 
4.3 
Justification for Dose 
No human trials of mRNA-1273 have been conducted to date. Preclinical evaluations will occur 
in parallel with this phase I clinical trial. In several ongoing Phase 1 dose-ranging studies 
(mRNA-1653, a combination vaccine against human metapneumovirus, hMPV and human 
parainfluenza type 3; mRNA-1647 and mRNA-1443, both CMV vaccines; mRNA-1893 against 
Zika virus) dosage levels of mRNA between 10 and 300 mcg were administered IM as one-, 
two- or three-dose vaccination schedules. Immunogenicity and reactogenicity increased in a 
dose-dependent manner. The dosage levels proposed for this trial (10 mcg, 25 mcg, 50 mcg, 100 
mcg, and 250 mcg) are within the range of previous trials. However, in support of development 
of mRNA-1273 for prophylaxis against SARS-CoV-2 infection, nonclinical immunogenicity, 
biodistribution, and safety studies have been completed with similar mRNA-based vaccines 
formulated in SM-102-containing LNPs. 
4.4 
Optional Third mRNA-1273 Vaccination Substudy 
All subjects in this clinical trial were scheduled to receive two mRNA-1273 vaccinations, 28 
days apart, at dosages of 25, 50, 100, or 250 mcg (seeTable 1), with the last scheduled follow-up 
visit occurring at 365 days after the second vaccination (see Table 4). During the course of the 
main study, interim efficacy data from a Phase 3 placebo-controlled clinical trial of mRNA-1273 
(COVE), administered as 2 doses of 100 mcg given 28 days apart, demonstrated vaccine efficacy 
of 94.1% (95% CI: 89.3%, 96.8%) for the prevention of symptomatic, confirmed COVID-19 

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(Baden, LR, et al. 2020). After review of the interim safety and efficacy data from that clinical 
trial, the FDA granted on December 18, 2020 an Emergency Use Authorization (EUA) for the 
mRNA-1273 vaccine in adults 18 years of age and older. 
To potentially enhance and extend the duration of protection provided by the 2-dose vaccination 
schedule of mRNA-1273 administered in the main study, and to gain an understanding of the 
immune responses to a third dose of mRNA-1273, subjects in the main study may participate in 
an optional third mRNA-1273 vaccination substudy, detailed in Section 12, Appendix A. 
Substudy subjects will receive a third mRNA-1273 vaccination, administered via an IM injection 
at a dosage of 100 mcg/0.5 mL, given six to twelve months after receipt of their second 
vaccination in the main study. Substudy subjects will be followed for safety, reactogenicity, and 
immunogenicity endpoints through 12 months post third vaccination (Substudy Day 366). 
To be eligible to participate in the substudy, subjects must have received both the first and 
second mRNA-1273 vaccinations in the main study. Other eligibility criteria are specified in 
Appendix A. Subjects who received only one mRNA-1273 vaccination in the main study will be 
advised to receive an FDA authorized or approved COVID-19 vaccine, according to the 
recommended schedule, when available to them outside of this trial, unless they have a 
contraindication to COVID-19 vaccines that are available. 
Subjects who elect not to participate in the optional third mRNA-1273 vaccination substudy or 
are not eligible for the substudy will continue to be followed according to the Schedule of 
Activities for the main study (see Table 4) with the Final Study Visit 14 occurring at Day 394 
(±14 days). 
Dosing for the optional third mRNA-1273 vaccination substudy is found in Table 13. 
Schedule of assessments for the optional third mRNA-1273 vaccination substudy is found in 
Table 14. 
Statistical Considerations for the optional third mRNA-1273 vaccination substudy are found in 
Section 12.11. 
5. 
STUDY POPULATION 
Up to one hundred and fifty-five (155) males and non-pregnant females, ≥18 years of age, who 
are in good health and meet all eligibility criteria will be enrolled. The target population should 
reflect the community at large. The estimated time from initiation of enrollment to complete 
enrollment in this clinical trial is approximately 16 weeks. Information regarding this trial may 
be provided to potential subjects who have previously participated in other vaccine trials 
conducted at the participating site. Other forms and/or mechanisms of recruitment may also be 
used. The IRB will approve the recruitment process and all materials prior to use. Screening can 
occur up to 42 days prior to the first dose. 
Subject Inclusion and Exclusion Criteria must be confirmed by a study clinician, licensed to 
make medical diagnoses and listed on the Form FDA 1572 as the participating site PI or 
appropriate sub-investigator. No exemptions are granted on Subject Inclusion or Exclusion 
Criteria in DMID-sponsored studies. 
5.1 
Inclusion Criteria 

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A subject must meet all of the following criteria to be eligible to participate in this study: 
1. Provides written informed consent prior to initiation of any study procedures. 
2. Be able to understand and agrees to comply with planned study procedures and be 
available for all study visits. 
3. Agrees to the collection of venous blood per protocol. 
4. Male or non-pregnant female, ≥18 years of age at time of enrollment. 
5. BMI 18.0-35.0 kg/m2, inclusive (<56 years of age), at screening; BMI 18.0-30.0 kg/m2, 
inclusive (≥56 years of age), at screening. 
6. Women of childbearing potential1 must agree to use or have practiced true abstinence2 or 
use at least one acceptable primary form of contraception.3,4 
Note: These criteria are applicable to females in a heterosexual relationship and child-
bearing potential (i.e., the criteria do not apply to subjects in a same sex relationship). 
1Not of childbearing potential – post-menopausal females (defined as having a history of 
amenorrhea for at least one year) or a documented status as being surgically sterile 
(hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure® 
placement). 
2True abstinence is 100% of time no sexual intercourse (male’s penis enters the female’s 
vagina). (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation 
methods] and withdrawal are not acceptable methods of contraception). 
3Acceptable forms of primary contraception include monogamous relationship with a 
vasectomized partner who has been vasectomized for 180 days or more prior to the 
subject’s first vaccination, intrauterine devices, birth control pills, and 
injectable/implantable/insertable hormonal birth control products. 
4Must use at least one acceptable primary form of contraception for at least 30 days 
prior to the first vaccination and at least one acceptable primary form of contraception 
for 60 days after the last vaccination. 
7. Women of childbearing potential must have a negative urine or serum pregnancy test 
within 24 hours prior to each vaccination. 
8. Male subjects of childbearing potential5: use of condoms to ensure effective 
contraception with a female partner of childbearing potential from first vaccination until 
60 days after the last vaccination. 
5Biological males who are post-pubertal and considered fertile until permanently sterile 
by bilateral orchiectomy or vasectomy. 
9. Male subjects agree to refrain from sperm donation from the time of first vaccination 
until 60 days after the last vaccination. 
10. In good health.6 
6As determined by medical history and physical examination to evaluate acute or ongoing 
chronic medical diagnoses/conditions that have been present for at least 90 days, which 
would affect the assessment of safety of subjects. Chronic medical diagnoses/conditions 

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should be stable for the last 60 days (no hospitalizations, ER, or urgent care for 
condition or need for supplemental oxygen). This includes no change in chronic 
prescription medication, dose, or frequency as a result of deterioration of the chronic 
medical diagnosis/condition in the 60 days before enrollment. Any prescription change 
that is due to change of health care provider, insurance company, etc., or done for 
financial reasons, and in the same class of medication, will not be considered a deviation 
of this inclusion criterion. Any change in prescription medication due to improvement of 
a disease outcome, as determined by the participating site PI or appropriate sub-
investigator, will not be considered a deviation of this inclusion criterion. Subjects may 
be on chronic or as needed (prn) medications if, in the opinion of the participating site PI 
or appropriate sub-investigator, they pose no additional risk to subject safety or 
assessment of reactogenicity and immunogenicity, and do not indicate a worsening of 
medical diagnosis/condition. Similarly, medication changes subsequent to enrollment and 
study vaccination are acceptable provided the change was not precipitated by 
deterioration in the chronic medical condition, and there is no anticipated additional risk 
to the subject or interference with the evaluation of responses to study vaccination. 
11. Oral temperature is less than 100.0°F (37.8°C). 
12. Pulse no greater than 100 beats per minute. 
13. Systolic BP is 85 to 150 mm Hg, inclusive. 
14. Clinical screening laboratory evaluations (WBC, Hgb, PLTs, ALT, AST, Cr, ALP, T. 
Bili, Lipase, PT, and PTT) are within acceptable normal reference ranges at the clinical 
laboratory being used. 
15. Must agree to have samples stored for secondary research. 
16. Agrees to adhere to Lifestyle Considerations (defined in Section 5.4) throughout study 
duration. 
17. Must agree to refrain from donating blood or plasma during the study (outside of this 
study). 
5.1.1 
Leukapheresis Inclusion Criteria 
A subject must meet all of the following criteria to be eligible for leukapheresis: 
1. Written informed consent for leukapheresis is provided. 
2. Weight ≥110 pounds. 
3. Screening laboratory evaluations are within acceptable ranges at the site where the 
leukapheresis procedure will be performed. 
4. Negative urine or serum pregnancy test within 48 hours of the leukapheresis procedure 
for women of childbearing potential. 
5. Adequate bilateral antecubital venous access. 
6. No use of blood thinners, aspirin or NSAIDs at least 5 days before the leukapheresis 
procedure. 

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7. Enrolled in cohorts 2, 3, 5, 10, or 11, and possibly cohort 6, if enrolled, and completed 
the two-dose vaccination series. 
5.2 
Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from participation in this 
study: 
1. Positive pregnancy test either at screening or just prior to each vaccine administration. 
2. Female subject who is breastfeeding or plans to breastfeed from the time of the first 
vaccination through 60 days after the last vaccination. 
3. Has any medical disease or condition that, in the opinion of the participating site PI or 
appropriate sub-investigator, precludes study participation.7 
7Including acute, subacute, intermittent or chronic medical disease or condition that 
would place the subject at an unacceptable risk of injury, render the subject unable to 
meet the requirements of the protocol, or may interfere with the evaluation of responses 
or the subject’s successful completion of this trial. 
4. Presence of self-reported or medically documented significant medical or psychiatric 
condition(s).8 
8Significant medical or psychiatric conditions include but are not limited to: 
Respiratory disease (e.g., chronic obstructive pulmonary disease [COPD], asthma) 
requiring daily medications currently or any treatment of respiratory disease 
exacerbations (e.g., asthma exacerbation) in the last 5 years. Asthma medications: 
inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short 
acting beta agonists, theophylline, ipratropium, biologics. 
Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, 
ischemic heart disease), history of myocarditis or pericarditis as an adult, myocardial 
infarction (MI) within past 6 months, coronary artery bypass surgery or stent placement, 
or uncontrolled cardiac arrhythmia. 
Neurological or neurodevelopmental conditions (e.g., history of migraines in the past 5 
years, epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic 
deficits, Guillain-Barré syndrome, encephalomyelitis, transverse myelitis, stroke or 
transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral 
sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease). 
Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding 
basal cell and squamous cell carcinoma of the skin, which are allowed. 
An autoimmune disease, including hypothyroidism without a defined non-autoimmune 
cause, localized or history of psoriasis. 
An immunodeficiency of any cause. 
Chronic kidney disease, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2. 

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5. Has an acute illness9, as determined by the participating site PI or appropriate sub-
investigator, with or without fever [oral temperature ≥38.0°C (100.4°F)] within 72 hours 
prior to each vaccination. 
9An acute illness which is nearly resolved with only minor residual symptoms remaining 
is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, 
the residual symptoms will not interfere with the ability to assess safety parameters as 
required by the protocol. 
6. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or 
HIV types 1 or 2 antibodies at screening. 
7. Has participated in another investigational study involving any investigational product10 
within 60 days, or 5 half-lives, whichever is longer, before the first vaccine 
administration. 
10study drug, biologic or device 
8. Currently enrolled in or plans to participate in another clinical trial with an 
investigational agent11 that will be received during the study-reporting period.12 
11Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or 
medication. 
1213 months after the first vaccination. 
9. Has previously participated in an investigational study involving LNPs (a component of 
the investigational vaccine assessed in this trial). 
10. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, 
generalized urticaria, angioedema, other significant reaction) to any previous licensed or 
unlicensed vaccines. 
11. Chronic use (more than 14 continuous days) of any medications that may be associated 
with impaired immune responsiveness.13 
13Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of 
prednisone equivalent, allergy injections, immunoglobulin, interferon, 
immunomodulators, cytotoxic drugs, or other similar or toxic drugs during the preceding 
6-month period prior to vaccine administration (Day 1). The use of low dose topical, 
ophthalmic, inhaled and intranasal steroid preparations will be permitted. 
12. Anticipating the need for immunosuppressive treatment within the next 6 months. 
13. Received immunoglobulins and/or any blood or blood products within the 4 months 
before the first vaccine administration or at any time during the study. 
14. Has any blood dyscrasias or significant disorder of coagulation. 
15. Has any chronic liver disease, including fatty liver. 
16. Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 
6 months before the first vaccine administration. 
17. Has a positive test result for drugs of abuse at screening or before the first vaccine 
administration. If cannabis is the only detected drug, inclusion is permitted. 

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18. Has any abnormality or permanent body art (e.g., tattoo) that would interfere with the 
ability to observe local reactions at the injection site (deltoid region). 
19. Received or plans to receive a licensed, live vaccine within 4 weeks before or after each 
vaccination. 
20. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or 
after each vaccination. 
21. Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any time 
prior to or during the study. 
22. Close contact of anyone known to have SARS-CoV-2 infection within 30 days prior to 
vaccine administration. 
23. History of COVID-19 diagnosis. 
24. On current treatment with investigational agents for prophylaxis of COVID-19. 
25. Current use of any prescription or over-the-counter medications within 7 days prior to 
vaccination, unless approved by the investigator or necessary to manage a chronic 
condition. 
26. Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment 
through 28 days after the last vaccination. 
27. Reside in a nursing home or other skilled nursing facility or have a requirement for 
skilled nursing care. 
28. Non-ambulatory. 
29. For subjects ≥56 years of age, history of chronic smoking within the prior year. 
30. For subjects ≥56 years of age, current smoking or vaping. 
31. For subjects ≥56 years of age, individuals currently working with high risk of exposure to 
SARS-CoV-2 (e.g., active health care workers with direct patient contact, emergency 
response personnel). 
5.2.1 
Exclusion of Specific Populations 
This is a first-in-human trial in healthy subjects, ≥18 years of age. Because the effects on the 
fetus are not known, pregnant women will not be eligible for the trial. Women of childbearing 
potential must utilize a highly effective method of contraception and will be required to have a 
negative urine or serum pregnancy test within 24 hours prior to each vaccination. Children will 
not be included in this trial as presently there are no safety or efficacy data in adults. Should the 
outcome of this trial be deemed acceptable, additional trials may be initiated, including those in 
other populations. 
5.3 
Inclusion of Vulnerable Subjects 
Not Applicable 
5.4 
Lifestyle Considerations 

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During this study subjects are asked to: 
• Refrain from consuming food or drink containing poppy seeds within 72 hours of the 
screening visit as this could cause a false positive urine drug screen result. 
• Follow public health guidance on preventing SARS-CoV-2 infection. 
• Subjects must not eat or drink anything hot or cold within 10 minutes prior to taking oral 
temperature. 
5.5 
Screen Failures 
After the screening assessments have been completed, the participating site PI or qualified 
designee is to review the inclusion and exclusion criteria and determine the subject’s eligibility 
for the study. 
Only the following information will be collected on screen failures: demographics (age, screen 
number, sex, ethnicity, and race) and reason for ineligibility. Subjects who are found to be 
ineligible will be told the reason for ineligibility. 
Individuals who do not meet the criteria for participation in this study (screen failure) because of 
an abnormal clinical laboratory finding may be rescreened once. 
5.6 
Strategies for Recruitment and Retention 
5.6.1 
Recruitment 
Potential subjects will learn about the study via IRB-approved recruitment strategies, including 
direct mailing, recruitment from an IRB-approved trial registry and local advertisements/flyers. 
Screening will begin with a brief IRB-approved telephone call from study staff. Information 
about the study will be presented to potential subjects and questions about their health and ability 
to comply with the study visit schedule will be asked of potential subjects to presumptively 
determine eligibility. Appointments will be made at the research clinic for potential subjects who 
are interested in the study for further screening procedures and additional protocol-specific 
information. 
5.6.2 
Retention 
Study retention strategies will include education and explanation of the study schedule and 
procedures during screening and enrollment visits and restriction of enrollment to persons who 
can attend all study visits. Participating subjects will be reminded of subsequent visits during 
each visit, and study staff will contact subjects prior to appointments. Study staff will contact 
subjects who miss appointments to encourage them to return for completion of safety 
evaluations. 
5.6.3 
Compensation Plan for Subjects 
Subjects may be compensated for their participation in this trial. Compensation will be in 
accordance with local IRB requirements, and subject to local IRB approval. Reimbursements 
will be disbursed at specific timepoints during the study with the amount contingent on 
completing study procedures. 

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5.6.4 
Costs 
There is no cost to subjects for the research tests, procedures/evaluations or study product while 
taking part in this trial. Procedures and treatment for clinical care may be billed to the subject, 
subject’s insurance or third party. 
6. 
STUDY PRODUCT 
6.1 
Study Product(s) and Administration 
6.1.1 
Study Product Description 
Product: mRNA-1273 
mRNA-1273 is an LNP dispersion containing an mRNA that encodes for the pre fusion 
stabilized spike protein SARS-CoV-2. mRNA-1273 consists of an mRNA Drug Substance that is 
manufactured into LNPs composed of the proprietary ionizable lipid, SM-102, and 3 
commercially available lipids, cholesterol, DSPC, and PEG2000 DMG. mRNA-1273 has a total 
lipid content of 9.7 mg/mL and is formulated at a concentration of 0.5 mg/mL in 20 mM 
trometamol (Tris) buffer containing 87 mg/mL sucrose and 10.7 mM sodium acetate, at pH 7.5. 
Diluent: 0.9% NaCl for injection, USP 
The USP grade 0.9% NaCl or normal saline for injection is a sterile, nonpyrogenic, isotonic 
solution; each mL contains NaCl 9 mg. It contains no bacteriostatic agent, antimicrobial agent, 
preservatives, or added buffer and is supplied only in single-dose containers. The solution may 
contain hydrochloric acid and/or sodium hydroxide for pH adjustment (pH 5.3, range 4.5-7.0). 
This product should be used to dilute the vaccine to the desired concentration. 
6.1.2 
Dosing and Administration 
mRNA-1273 (0.5 mg/mL) will be diluted in 0.9% NaCl for injection, USP to obtain 10, 25, 50, 
100, and 250 mcg in 0.5 mL dosages. Each dose will be administered via IM injection (0.5 mL) 
into the deltoid muscle on Days 1 and 29. The second dose of vaccine (0.5 mL) will be 
administered preferably in the same arm used for the first dose. The pharmacist will prepare a 
single dose (0.5 mL) for each subject based on cohort assignment. 
Table 7: Dosing and Administration 
Cohort 
Product 
Name 
Dose 
Route 
Frequency of 
Administration 
1 
mRNA-1273 
25 mcg 
IM 
D1, D29 
2 
mRNA-1273 
100 mcg 
IM 
D1, D29 
3 
mRNA-1273 
250 mcg 
IM 
D1, D29 
4 
mRNA-1273 
25 mcg 
IM 
D1, D29 
5 
mRNA-1273 
100 mcg 
IM 
D1, D29 
6* 
mRNA-1273 
250 mcg 
IM 
D1, D29 
7 
mRNA-1273 
25 mcg 
IM 
D1, D29 
8 
mRNA-1273 
100 mcg 
IM 
D1, D29 
9* 
mRNA-1273 
250 mcg 
IM 
D1, D29 
10 
mRNA-1273 
50 mcg 
IM 
D1, D29 

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Cohort 
Product 
Name 
Dose 
Route 
Frequency of 
Administration 
11 
mRNA-1273 
50 mcg 
IM 
D1, D29 
12 
mRNA-1273 
50 mcg 
IM 
D1, D29 
13* 
mRNA-1273 
10 mcg 
IM 
D1, D29 
*Cohorts 6, 9 and 13 were not enrolled. 
See the protocol-specific Manual of Procedures (MOP) for detailed information on the 
preparation, labeling, storage, and administration of vaccine for each cohort. Vaccine preparation 
will be performed by the participating site’s research pharmacist on the same day of vaccine 
administration to the subject. 
Visually inspect the mRNA-1273 upon receipt and prior to use. If the study product(s) appear(s) 
to have been damaged, contaminated or discolored, contain(s) visible particulate matter, or if 
there are any concerns regarding the integrity, do NOT use the affected study product(s). The 
affected study product(s) must be quarantined at appropriate storage temperature and labeled as 
‘Do Not Use’ (until further notice). The participating site PI or responsible person should 
immediately contact the DMID Product Support Team at 
DMIDProductSupportTeam@niaid.nih.gov and DMID Clinical Project Manager for further 
instructions before any additional vaccinations are administered. Based on the information 
collected, DMID and/or the manufacturer will determine whether the affected study product(s) 
can be used. If the affected study product(s) cannot be used, the participating site will receive 
specific instructions on how to return the affected study product(s) to the DMID Clinical 
Material Services (CMS) or destroy the affected study product(s) on-site. If the mRNA-1273 is 
unusable, study staff will use another vial from the study supply. Replacement vials may be 
requested by contacting DMID. Additional instructions for quarantine and DMID contact 
information are provided in the protocol-specific MOP. 
The injection dose volume (0.5 mL each) of vaccine should be withdrawn from the final mixed 
vial(s) or compounding vial(s) containing the prepared dosing solution. The number of 
individual dosing syringes that may be filled from one mixing vial varies depending on the 
dosage. Doses for multiple subjects may be drawn into individual dosing syringes (0.5 mL each) 
from the same mixing vial within 30 minutes of completion of dosing solution preparation (10, 
25, 50, and 100 mcg doses only). Gently invert the final mixed vial(s) or the compounding 
vial(s) 20 times until components are mixed prior to withdrawing. Do not mix vigorously or 
sonicate or vortex. 
Aseptic technique will be used for the withdrawal and administration of each dose of vaccine 
using a disposable, sterile needle appropriate in length for each subject and a 1-mL disposable, 
sterile syringe. 
The expiration time of the dosing syringe containing the prepared mRNA-1273 solution is 4 
hours at room temperature for the 10 mcg dosage after the solution is drawn into the dosing 
syringe and 8 hours at room temperature for the 25, 50, 100, and 250 mcg dosages after the 
solution is drawn into the dosing syringe. 
6.1.3 
Dose Escalation 
Section 4.1. 

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6.1.4 
Dose Modifications 
No dose modifications. 
6.2 
Accountability/Handling/Storage/Preparation 
6.2.1 
Acquisition and Accountability 
Product: mRNA-1273 
Will be provided by ModernaTX, Inc. via the DMID CMS. 
Upon request by DMID, mRNA-1273 will be transferred to the following address: 
DMID Clinical Materials Services Contract 
Fisher BioServices 
20439 Seneca Meadows Parkway 
Germantown, MD 20876 
Phone: 240-477-1350 
Fax: 240-477-1360 
Email: DMID.CMS@thermofisher.com 
Diluent: 0.9% NaCl for injection, USP 
Will be provided by DMID via the DMID CMS. 
All study products will be shipped to the clinical research site upon request and approval from 
DMID. 
Accountability 
The participating site PI is responsible for study product distribution and disposition and has 
ultimate responsibility for study product accountability. The participating site PI may delegate to 
the participating site’s research pharmacist responsibility for study product accountability. The 
participating site’s research pharmacist will be responsible for maintaining complete records and 
documentation of study product receipt, accountability, dispensation, storage conditions, and 
final disposition of the study product(s). Study product accountability records and dispensing 
logs should include, but are not limited to the following: DMID protocol number; name, dosage 
form, strength of the study product; capture vial numbers assigned sequentially by the 
pharmacists as vials/syringes are used (number uniquely, do not start over at 1 or repeat 
numbers), manufacturer or other source; control, lot number or other identification number; 
expiration or retest date; date of receipt of the study product; quantity received from supplier; 
subject identification number; quantity dispensed as amount or dose per subject; balance of study 
product currently available; disposition of study product if not dispensed to a study subject (e.g., 
disposed/destroyed or retuned to supplier as per protocol or protocol-specific MOP or as directed 
by DMID); date of vaccine preparation/administration, time of vaccine preparation, expiration of 
vaccine preparation; and amount of vaccine withdrawn for administration. Time of vaccine 
administration to the subject will be recorded on the appropriate data collection form (DCF). All 
study product(s), including the amount of mRNA-1273, diluent (0.9% NaCl for injection, USP), 
and vial admixtures, whether administered or not, must be documented on the appropriate study 
product accountability record or dispensing log. The sponsor’s monitoring staff will verify the 

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participating site’s study product accountability records and dispensing logs per the DMID-
approved clinical monitoring plan (CMP). 
Once all subject dosing is complete, the pharmacy staff should retain or dispose of used study 
products and complete study product accountability procedures in accordance with site-specific 
standard operating procedures (SOPs). This applies to: 
• used and unused mRNA-1273 vials 
• used mixing vials 
• mRNA-1273 cartons 
All used supplies noted above may either be sequestered from the unused supplies and retained 
until study conclusion or until study product accountability has occurred by the monitor and 
written notification stating retention is no longer required is received, or may be destroyed in 
accordance with site-specific SOPs with a second pharmacy staff member’s observation and 
verification as documented in the pharmacy log. Refer to the protocol-specific MOP for details 
on storing used mRNA-1273 vials, used 0.9% NaCl Injection vials and used mixing vials. 
Destruction 
After the study treatment period has ended or as appropriate over the course of the study after 
study product accountability has been performed, disposition of unused and used mRNA-1273 
vials should occur as noted: 
• Unused and Used mRNA-1273 vials: 
o Should be destroyed on-site following applicable site procedures or by the site’s 
selected destruction vendor. Following the site’s procedure for the destruction of 
hazardous material or study product destruction policy/SOP when destroying used 
and unused items. 
o A certificate of destruction or documentation of destruction should be provided to 
the sponsor and retained in the Pharmacy Binder once completed. 
Used syringes may be destroyed in accordance with site-specific SOPs. 
6.2.2 
Formulation, Appearance, Packaging, and Labeling 
Product: mRNA-1273 
mRNA-1273 is provided as a sterile liquid for injection, white to off white dispersion in 
appearance, at a concentration of 0.5 mg/mL in 20 mM Tris buffer containing 87 mg/mL sucrose 
and 10.7 mM sodium acetate, at pH 7.5. 
Diluent: 0.9% NaCl for injection, USP 
The USP grade 0.9% NaCl or normal saline for injection is a sterile, nonpyrogenic, isotonic 
solution; each mL contains NaCl 9 mg. It contains no bacteriostatic agent, antimicrobial agent, 
preservatives, or added buffer and is supplied only in single-dose containers. It is clear in 
appearance, and available in 10 mL vials. 
Each of the study products will be labeled according to manufacturer specifications and include 
the statement “Caution: New Drug Limited by Federal Law to Investigational Use.” 

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Sterile empty vials (2-mL or 10-mL) will be provided with latex-free stoppers. 
6.2.3 
Product Storage and Stability 
Product: mRNA-1273 
mRNA-1273 is stored at -70°C (-60°C to -90°C). 
Stability protocols for mRNA-1273 will include at least 24-months duration at the intended 
storage temperature (-60°C to -90°C). 
Stability and compatibility with the apparatus intended for administration for up to 8 hours after 
preparation were assessed. The prepared doses were stable for clinical in-use for up to 8 hours at 
room temperature (Note: up to 4 hours at room temperature for 10 mcg doses). 
Diluent: 0.9% NaCl for injection, USP 
0.9% NaCl for injection, USP is stored at 20 to 25°C (68 to 77°F) [See USP Controlled Room 
Temperature.] 
The temperature of the storage unit must be manually recorded daily (excluding non-business 
days and holidays, as applicable) and continuously monitored and recorded during the course of 
this trial per site-specific SOPs, and documentation will be maintained. If the temperature 
fluctuates outside of the required range, the affected study product(s) must be quarantined at the 
correct storage temperature and labeled as ‘Do Not Use’ (until further notice). The participating 
site’s research pharmacist must alert the participating site PI and study coordinator, if the 
temperature fluctuates outside of the required range. In the event the temperature fluctuates 
outside of the required range, including accidental deep-freezing or disruption of the cold chain, 
the affected study product(s) must not be administered. The participating site PI or responsible 
person should immediately contact the DMID Product Support Team at 
DMIDProductSupportTeam@niaid.nih.gov for further instructions before any additional 
vaccinations are administered. Based on the information collected, DMID and/or the 
manufacturer will determine whether the affected study product(s) can be used. If it cannot be 
used, the participating site will receive specific instructions on how to return the affected study 
product(s) to the DMID CMS or destroy it on-site. Additional instructions for quarantine and 
DMID contact information are provided in the protocol-specific MOP. 
mRNA-1273 must be stored in a secure area with limited access (pharmacy staff only), and must 
be stored frozen at -60°C to -90°C. The freezer should have an automated temperature recording 
and alert system. There must be an available back-up freezer. The freezers must be connected to 
a back-up generator; or alternate plan in the event of a power failure. The pharmacy must have in 
place a 24-hour alert system that allows for rapid response in case of freezer malfunctioning. In 
addition, vaccine accountability study staff (e.g., pharmacy staff) are required to keep a 
temperature log to establish a record of compliance with these storage conditions. Only vaccine 
accountability study staff (e.g., pharmacy staff) should have access to the product used in this 
study. The participating site is responsible for reporting any mRNA-1273 that was not 
temperature controlled during shipment or during storage to the pharmacy staff. Such mRNA-
1273 will be retained for inspection by the pharmacy staff and disposed of according to approved 
methods. 
6.2.4 
Preparation 

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Refer to the protocol-specific MOP for details about preparation. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Treatment Assignment Procedures 
Per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) guideline E6: GCP, screening records will be kept at the participating site to 
document the reason why an individual was screened, but failed trial entry criteria. The reasons 
why individuals failed screening will be recorded in the Statistical and Data Coordinating 
Center’s (SDCC) Advantage eClinicalSM (Electronic Data Capture System). 
Once consented and upon entry of demographic data and confirmation of eligibility for this trial, 
the subjects will be enrolled. Enrollment will proceed in a staged fashion. Sentinel subject dosing 
will begin with 4 subjects in cohort 1 (25 mcg). The 4 sentinel subjects for cohort 2 (100 mcg) 
will be enrolled no earlier than one day after enrollment of the last of the 4 sentinel subjects in 
cohort 1. If no halting rules have been met after the 8 sentinel subjects have completed Day 5, 
then full enrollment will proceed first with the remaining subjects in cohort 1, followed by the 
remaining subjects in cohort 2 without interruption. If no halting rules have been met after all 
subjects in cohort 2 have completed Day 8, then dosing of 4 sentinel subjects will begin in cohort 
3. If no halting rules have been met after the 4 sentinel subjects in cohort 3 have completed Day 
5, then full enrollment of cohort 3 will proceed. 
If no halting rules have been met after all subjects in cohorts 1 and 2 have completed Day 8, 
dosing will begin for cohorts 4 (25 mcg; 56-70 years of age) and 5 (100 mcg; 56-70 years of 
age). If no halting rules have been met after all subjects in cohorts 4 and 5 have completed Day 
8, dosing will begin for cohorts 7 (25 mcg; ≥71 years of age) and 8 (100 mcg; ≥71 years of age). 
Based on the interim immunogenicity data available as of May 15, 2020, enrollment into cohorts 
6 and 9 (250 mcg; 56-70 years of age and ≥71 years of age) will be deferred in order to explore 
lower dosages. Therefore, enrollment of cohorts 10-12 (50 mcg; 18-55 years of age, 56-70 years 
of age and ≥71 years of age) will be prioritized. Subjects will be enrolled simultaneously in 
cohorts 10-12; there will be no staging. To further explore dosage sparing, cohort 13 (10 mcg 
dose; 18-55 years of age) may be enrolled. A decision regarding the enrollment of cohorts 6, 9 
and 13 will be made after review of interim immunogenicity data from cohorts 1-5, 7, 8, and 10-
12. 
If no halting rules have been met after all subjects in cohorts 5 and 8 have completed Day 8, 
dosing will begin concurrently for cohorts 10-12. If no halting rules have been met after all 
subjects in cohorts 3, 7 and 8 have completed Day 8, dosing may begin for cohort 6, if enrolled. 
If no halting rules have been met after all subjects in cohort 6 have completed Day 8, dosing may 
begin for cohort 9, if enrolled. 
6.3.2 
Randomization and Blinding 
This is an open-label study with sequential group enrollment so randomization and blinding will 
not be utilized. 
6.3.3 
Blinding and Masking Procedures 
Not Applicable 

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6.4 
Study Intervention Compliance 
Each dose of study product will be administered by a member of the clinical research team that is 
qualified and licensed to administer the study product. Administration and date, time, and 
location of injection will be recorded on the appropriate DCF. 
6.5 
Concomitant Therapy 
Information about prior medications, including hormonal contraceptives, taken by the subject in 
the 30 days prior to providing informed consent will be recorded on the appropriate DCF. 
Concomitant medications include all medications (prescription, over the counter, supplements, 
and vaccines received outside of the study) taken by the subject from the time the informed 
consent is signed through Day 394. At each study visit following dosing, including telephone 
calls, subjects will be queried about new concomitant medications and changes to existing 
medications. 
Medications that might interfere with the evaluation of the investigational product should not be 
used by the subject during the study-reporting period (12 months after the second vaccination) 
unless clinically indicated as part of the subject’s health care. 
In the event medical conditions dictate the use of medications, subjects are encouraged to obtain 
adequate care, comply with the course of therapy as prescribed by their physician, and inform the 
study Investigator as soon as practical. Any drug or vaccine used or received by the subject 
during the trial should be recorded on the appropriate DCF. 
6.5.1 
Rescue Medicine 
Not Applicable 
6.5.2 
Non-Research Standard of Care 
Not Applicable 
7. 
STUDY INTERVENTION DISCONTINUATION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Halting Criteria and Discontinuation of Study Intervention 
7.1.1 
Halting Criteria 
The study will be paused if any of the following events occur: 
1- Any subject experiences an SAE after administration of the vaccine that is considered 
related to vaccine. 
2- Any subject experiences laryngospasm, bronchospasm or anaphylaxis within 24 hours 
after administration of vaccine that is considered related to vaccine. 
3- Any subject experiences ulceration, abscess or necrosis at the injection site that is 
considered related to vaccine administration. 

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4- Two (2) or more subjects experience an allergic reaction such as generalized urticaria 
(defined as occurring at three or more body parts) within 72 hours after administration of 
vaccine that is considered related to vaccine. 
5- Three (3) or more subjects experience a Grade 3 AE (unsolicited and/or clinical 
laboratory abnormality), in the same Preferred Terms based on the Medical Dictionary 
for Regulatory Activities (MedDRA) coding, that lasted at least 48 hours after 
administration of the vaccine and is considered related to the vaccine. Clinical laboratory 
abnormalities are not subject to the time window. 
Study product administration and enrollments may resume only after review of the AEs that 
caused the pause results in a recommendation to permit further study product administration and 
enrollments. 
7.1.2 
Sentinel Halting Criteria 
If any of the following events occur to the sentinel subjects, the study will be paused: 
1- Any subject experiences ulceration, abscess or necrosis at the injection site. 
2- Any subject experiences laryngospasm, bronchospasm or anaphylaxis within 24 hours 
after administration of vaccine. 
3- Any subject experiences generalized urticaria (defined as occurring at three or more body 
parts) within 72 hours after administration of vaccine. 
4- Any subject experiences an SAE (except for accident or trauma) after administration of 
the vaccine that is considered related to the vaccine. 
5- Any 2 subjects in the same cohort experience the same Grade 3 Solicited Local AE or 
Systemic AE, (excluding measured grades of erythema and edema/induration alone) that 
lasted at least 48 hours within 7 days after administration of the vaccine. 
6- Any 2 subjects experience the same Grade 3 AE (unsolicited and/or clinical laboratory 
abnormality), in the same Preferred terms based on the MedDRA coding, that lasted at 
least 48 hours after administration of the vaccine and is considered related to the vaccine. 
Clinical laboratory abnormalities are not subject to the time window. 
7.1.3 
Criteria for Continuation of Dosing and Redosing 
In the event a halting rule is met: 
• an unscheduled safety analysis by the SMC will be required for approval of further 
enrollment, and 
• further administration of the vaccine, including a second dose, is suspended for ALL 
subjects until an assessment by the SMC takes place. 
7.1.3.1 
Withdrawal Criteria for Second Study Vaccination 
Prior to receiving the second vaccination, subjects will be reassessed. The following events 
constitute contraindications to any further administration of vaccines. If any of these events 
occur during the study, the subject must not receive the second vaccination but will be 

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encouraged to continue study participation for safety and immunogenicity evaluations through 
12 months after their last vaccination. 
• Withdrawal of consent. 
• As deemed necessary by the participating site PI or appropriate sub-investigator for non-
compliance or other reasons. This may include previously undisclosed or new conditions 
that meet exclusion criteria. 
• Any clinically significant medical condition that, in the opinion of the participating site 
PI or appropriate sub-investigator, poses an additional risk to the subject if he/she 
continues to participate in the study. 
• Anaphylaxis or unexpected systemic hypersensitivity reaction following the 
administration of the first vaccination. 
• Any SAE judged to be related to vaccine. 
• Pregnancy. 
• Subject is lost to follow-up. 
• New information becomes available that makes further participation unsafe. 
• 
Termination of this trial. 
7.1.3.2 
Delay of Study Vaccination 
If any of these events occur at the time scheduled for vaccination, the subject may be vaccinated 
at a later date, within the window specified in the SOA, or the subject may be withdrawn from 
dosing at the discretion of the participating site PI or appropriate sub-investigator: 
• 
Acute moderate or severe infection with or without fever at the time of vaccination. 
• 
Fever, defined as oral temperature ≥38.0°C (100.4°F) at the time of vaccination. 
Subjects with a minor illness without fever, as assessed by the participating site PI or appropriate 
sub-investigator, can be administered vaccines. Subjects with an oral temperature of 38.0°C 
(100.4°F) or higher will be re-contacted within the window specified in the SOA and re-
evaluated for eligibility. 
7.1.4 
Follow-up for Subjects that Discontinued Study Intervention 
Discontinuation of study intervention does not require discontinuation from the study, and the 
remaining study procedures should be completed as indicated by the SOA. If a clinically 
significant finding is identified, including, but not limited to, changes from baseline, after 
enrollment, the participating site PI or qualified designee will determine if any change in subject 
management is needed. Any new clinically relevant finding will be reported as an AE. 
The data to be collected at the time of study intervention discontinuation should include the 
following: 
• Clinical safety laboratory evaluations. 
• Complete physical examination. 

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• Vital signs (BP, heart rate [HR], oral temperature). 
• Immunogenicity evaluations. 
7.2 
Subject Withdrawal from the Study and Replacement 
Subjects are free to withdraw from participation in the study at any time upon request, without 
any consequence. 
A study subject will be discontinued from participation in the study if any of the following 
reasons occur prior to initial dosing: 
• Request by the subject to terminate participation. 
• Vaccine is not administered. 
A subject may be removed from the study for the following reasons post initial dosing; however, 
whenever possible the subject should be followed for safety and immunogenicity evaluations per 
protocol: 
• Subject becomes pregnant before receiving the second dose of vaccine. 
• Study non-compliance to protocol requirements that in the opinion of the participating 
site PI or appropriate sub-investigator poses an increased risk (e.g., missing safety labs) 
or compromises the validity of the data. 
• Lost to follow-up. 
• If the subject met an exclusion criterion for participation in the study (either newly 
developed or not previously recognized) that precludes further study participation. 
• Request of primary care provider; the IRB, FDA, or NIAID. 
• Medical disease or condition, or new clinical finding(s) for which continued 
participation, in the opinion of the participating site PI or appropriate sub-investigator 
might compromise the safety of the subject, interfere with the subject’s successful 
completion of this study, or interfere with the evaluation of responses. 
• If any AE, clinical laboratory abnormality or situation occurs such that continued 
participation in the study would not be in the best interest of the subject. 
• The occurrence of an SAE. 
If the subject agrees, every attempt will be made to follow all AEs through resolution or 
stabilization. 
Subjects who withdraw, or are withdrawn from this study, or are lost to follow-up after signing 
the informed consent form (ICF) and administration of the study product will not be replaced. 
Subjects who withdraw, or are withdrawn from this study, or are lost to follow-up after signing 
the ICF but before administration of the study product may be replaced. 
The reason for subject discontinuation or withdrawal from the study will be recorded on the 
appropriate DCF. 

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7.3 
Lost to Follow-Up 
A subject will be considered lost to follow-up if he or she fails to appear for a follow-up 
assessment. Extensive effort (i.e., generally three documented contact attempts via telephone 
calls, e-mail, etc., made on separate occasions) will be made to locate or recall the subject, or at 
least to determine the subject’s health status. These efforts will be documented in the subject’s 
study file. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Screening and Immunogenicity Assessments 
8.1.1 
Screening Procedures 
There is a small amount of risk to subjects who report that they are in good health but have an 
unknown health problem at the time of screening. Screening assessments can occur up to 42 days 
before the subject’s first vaccination (Day 1) and may occur in one or two visits. At the first visit, 
and prior to any other study-related activities, the participating site PI or appropriate sub-
investigator will provide the subject with detailed study information and will obtain written 
informed consent. 
Some or all of the following assessments are performed during the screening visit to determine 
eligibility requirements as specified in the inclusion and exclusion criteria: 
• 
Obtain medical history. 
• 
Review pre-study medications and therapies up to 30 days prior to the start of screening 
and record on the appropriate DCF. 
• 
Review of adult vaccinations, including any other SARS-CoV-2 or other experimental 
coronavirus vaccines. 
• 
Measure vital signs (HR, BP, and oral temperature) and height and weight for 
determination of BMI. 
• 
Perform full physical examination which will include assessments of the following 
organs and organ systems: skin, head, ears, eyes, nose, and throat (HEENT), neck, lungs, 
heart, liver, spleen, abdomen, extremities, lymph nodes (axillary and cervical), and 
nervous system. 
• 
Review of birth control history with female subjects. 
• 
Counsel subjects to use adequate birth control methods required during the trial to avoid 
pregnancy. 
• 
Obtain blood and urine for clinical screening laboratory evaluations: 
o Hematology 
▪ 
WBCs 
▪ 
Hgb 
▪ 
PLTs 
o Chemistry (fasting or non-fasting) 

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▪ ALT 
▪ AST 
▪ ALP 
▪ T. Bili 
▪ Lipase 
▪ Cr 
▪ PT 
▪ PTT 
o Serology 
▪ Hepatitis B surface antigen 
▪ Hepatitis C virus antibody 
▪ HIV types 1 and 2 antigen/antibody 
o Serum pregnancy test (in women of childbearing potential) 
o Urine drug screen 
• 
Review inclusion and exclusion criteria. 
Clinical screening laboratory evaluations will be performed locally by the site laboratory. The 
volume of venous blood to be collected for these evaluations is presented in Table 8. 
The overall eligibility of the subject to participate in the study will be assessed once all screening 
values are available. The screening process can be suspended prior to complete assessment at 
any time if exclusions are identified by the study team. 
Study subjects who qualify for inclusion will be contacted and scheduled for enrollment and first 
vaccination within the window for enrollment. 
If a physiologic parameter, e.g., vital signs or clinical laboratory value, is outside of the protocol-
specified range, then the measurement may be repeated once if, in the judgment of the 
participating site PI or appropriate sub-investigator, the abnormality is the result of an acute, 
short-term, rapidly reversible condition (e.g., stress, anxiety or “white coat syndrome”) or other 
source of error. A physiologic parameter may also be repeated if there is a technical problem 
with the measurement caused by malfunctioning, or an inappropriate measuring device (i.e., 
inappropriate-sized BP cuff). 
A subject may be re-screened if there is a transient disease status (e.g., subject complained of a 
“cold or fever” and met a temporary delaying enrollment criterion of acute illness or fever), or if 
a protocol eligibility criterion that is not met at the initial time of screening, will be met by 
rescreening at a later date (e.g., a medication taken within exclusionary window at the time of 
first screening that would not be within exclusionary window at a later rescreen). 
No subjects may be screened more than twice due to a screening failure result as defined above. 

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Subjects will be provided the results of abnormal clinical laboratory test values or abnormal 
clinical findings necessitating follow-up at the discretion of the participating site PI or 
appropriate sub-investigator. Research laboratory results will not be provided to the subject. 
8.1.2 
Screening Procedures for Leukapheresis 
For those subjects consented for leukapheresis, screening procedures, including screening 
laboratory evaluations, will be performed locally prior to the leukapheresis procedure. Refer to 
the protocol-specific MOP for details on the leukapheresis procedure. 
8.1.3 
Immunogenicity Evaluations 
Serological Immunogenicity Assays: 
The following serological immunogenicity assays will be performed: 
• IgG ELISA to the SARS-CoV-2 S (spike) protein. 
• IgM and IgA ELISA to the SARS-CoV-2 S (spike) protein. 
• Neutralization assay using a SARS-CoV-2 pseudovirus. 
• Neutralization assay using a live wild-type SARS-CoV-2. 
Preparation of blood samples and shipping instructions for serological immunogenicity assays 
are outlined in the protocol-specific MOP. Inability (e.g., loss of IV access) to collect all baseline 
samples on Day 1 will not exclude the subject from further participation in this study as long as a 
minimum of baseline serum for serological immunogenicity assays is collected. 
Cellular Immunology Assays: 
This trial will also investigate T cell immune responses using multiparametric flow cytometry. 
Preparation of blood samples and shipping instructions for cellular immunology assays are 
outlined in the protocol-specific MOP. 
The volume of venous blood to be collected for immunogenicity evaluations is presented in 
Table 8. 
8.1.4 
Samples for Genetic/Genomic Analysis 
8.1.4.1 
Genetic/Genomic Analysis 
Stored PBMCs, including leukocyte samples obtained by leukapheresis, may be used in 
secondary research for sequencing of DNA from B cells to characterize B cell receptors and 
monoclonal antibodies. The DNA data may be used to synthesize antigen-specific antibodies to 
characterize antibody binding. Secondary research samples may also be used for other genomic 
analysis, including, but not limited to, single nucleotide polymorphisms (SNP) arrays, human 
leukocyte antigen (HLA) typing, transcriptomic analysis, evaluation of the immune response to 
the vaccine, and/or evaluation of any AE from the vaccine. 
8.1.4.2 
Genetic Privacy and Confidentiality 
Any genetic data generated will be kept private. Informed consent permitting data sharing will be 
part of the consent process. Subjects will be informed that the evolution of genomic technology 

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and analytical methods raises the risk of re-identification, even when specimens are de-
identified. No data that may identify specific subjects will be kept with the genetic data. 
8.1.4.3 
Management of Results 
All genetic testing in this protocol will be performed for research only and is not performed in a 
Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Therefore, results 
will not be shared with the subjects. 
8.2 
Safety and Other Assessments 
Study procedures are specified in the SOA. A study clinician, licensed to make medical 
diagnoses and listed on the Form FDA 1572 as the participating site PI or appropriate sub-
investigator, will be responsible for all study-related medical decisions. 
• Medical history: 
o A complete medical history will be obtained by interview of subjects at the 
screening visit. Subjects will be queried regarding a history of significant medical 
disorders of the head, ears, eyes, nose, throat, mouth, cardiovascular system, 
lungs, gastrointestinal tract, liver, pancreas, kidney, urologic system, nervous 
system, blood, lymph nodes, endocrine system, musculoskeletal system, skin, and 
genital/reproductive tract. A history of any allergies, cancer, immunodeficiency, 
psychiatric illness, substance abuse, and autoimmune disease will be solicited. 
o At all subsequent visits an interim medical history will be obtained by interview 
of subjects and any changes since the previous clinic visit or telephone call will be 
noted. The interim medical history should include an assessment for new medical 
conditions and symptoms suggestive of Protocol Specified AESIs, MAAEs and 
NOCMCs. 
• Physical examination: 
o A full physical examination will be performed at the screening visit and a 
symptom-directed (targeted) physical examination will be performed if indicated 
at all other timepoints specified in the SOA. 
▪ A full physical examination will include assessments of the following 
organs and organ systems: skin, HEENT, neck, lungs, heart, liver, spleen, 
abdomen, extremities, lymph nodes (axillary and cervical), and nervous 
system. 
▪ Height and weight will be measured, and BMI calculated, at the screening 
visit only. 
o A symptom-directed (targeted) physical examination will be performed if 
indicated at all other timepoints specified in the SOA. 
▪ Targeted physical examinations should also include an assessment for 
signs suggestive of Protocol Specified AESIs, MAAEs and NOCMCs. 
Interim or unscheduled physical examinations will be performed at the 

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discretion of the participating site PI or appropriate sub-investigator, if 
necessary, to evaluate AEs or abnormal clinical laboratory test results. 
o Reactogenicity assessments of solicited AEs occurring from the time of each 
vaccination through 7 days post each vaccination, will include an assessment of 
injection site reactions–erythema, edema/induration and pain, as well as systemic 
reactions–fever, fatigue, chills, myalgia (exclusive of the injection site), 
arthralgia, headache, and nausea. Pre-administration reactogenicity assessments 
will be performed immediately prior to each vaccination to establish baseline, 
then the vaccination will be given. 
o Subjects will be observed in the clinic for at least 60 minutes post each 
vaccination. The vaccination site will be examined, post-administration 
reactogenicity assessments will be performed, and any AEs/SAEs will be 
recorded on the appropriate DCF prior to discharge from the clinic. The 
vaccination site will also be examined on Days 8 and 36. 
• Vital signs: Vital sign measurements will include systolic and diastolic BP, HR, and oral 
temperature. Vital signs will be measured at timepoints specified in the SOA. On Days 1 
and 29, vital sign measurements will be collected prior to vaccine administration. Vital 
signs assessed on Day 1 prior to the first vaccination will be considered as baseline. 
Subjects must not eat or drink anything hot or cold within 10 minutes prior to taking oral 
temperature. 
• Clinical laboratory evaluations: 
o Fasting is not required before collection of clinical laboratory evaluations. 
o Serum pregnancy test will be performed locally by the site laboratory at the 
screening visit, and urine or serum pregnancy test will be performed locally by the 
site laboratory within 24 hours prior to each vaccination on Days 1 and 29, and as 
needed at interim or unscheduled visits for all women of childbearing potential. 
Results must be confirmed as negative prior to enrollment on Day 1 and 
administration of each vaccination. 
o Serology: hepatitis B surface antigen, hepatitis C virus antibody, and HIV types 1 
and 2 antigen/antibody at the screening visit only. 
o Urine drug screen for drugs of abuse (components per the standard panel at the 
site laboratory) at the screening visit only. 
o Clinical screening laboratory evaluations (WBCs, Hgb, PLTs, ALT, AST, ALP, 
T. Bili, Cr, Lipase, PT, and PTT) will be collected at the screening visit. 
▪ Clinical screening laboratory evaluations will be performed locally by the 
site laboratory. The volume of venous blood to be collected for clinical 
screening laboratory evaluations is presented in Table 8. 
o Clinical safety laboratory evaluations (WBCs, Hgb, PLTs, ALT, AST, ALP, T. 
Bili, Cr, and Lipase) collected immediately prior to the first vaccination will serve 
as the baseline (Day 1), and will be repeated on Days 8, 29 and 36. 

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▪ Clinical safety laboratory evaluations will be performed locally by the site 
laboratory. The volume of venous blood to be collected for clinical safety 
laboratory evaluations is presented in Table 8. Inability (e.g., loss of IV 
access) to collect all baseline samples on Day 1 will not exclude the 
subject from further participation in this study as long as a minimum of 
baseline clinical safety laboratory evaluations is collected. 
o Blood and urine will be collected at timepoints specified in the SOA. 
• Memory aid: 
o All subjects will complete a Memory Aid from the time of each vaccination 
through 7 days post each vaccination (Days 1-8 for the first vaccination, and Days 
29-36 for the second vaccination). Memory Aids will be reviewed with the 
subjects for any AEs (solicited injection site and systemic reactions, as well as 
unsolicited AEs), SAEs and concomitant medications during telephone calls on 
Days 2, 3, 30, and 31 and at clinic visits on Days 8 and 36. 
• Telephone call: 
o Subjects will be contacted by telephone to query for safety events. AEs that have 
occurred since the previous clinic visit or telephone call will be solicited. Based 
on the information collected, subjects may be asked to return to the clinic for 
evaluation. 
• Leukapheresis (only for those subjects consented for leukapheresis): 
o To support development of diagnostics, therapeutics and vaccines, a subset of 
subjects enrolled in cohorts 2, 3, 5, 10, and 11 may undergo leukapheresis to 
collect additional samples for secondary research. If enrollment in cohort 6 
proceeds, a subset of subjects in this cohort may also undergo leukapheresis. 
o Leukapheresis is an outpatient procedure during which leukocytes will be 
selectively harvested; red cells and other blood components will be returned to the 
subject. In a typical leukapheresis procedure, approximately 1-3 x109cells can be 
isolated with only minimal loss of red blood cells. No sedation is required. The 
procedure will be done by trained site staff and will be done using devices and 
procedures that conform to standard guidelines and SOPs. 
o For those subjects consented for leukapheresis, screening procedures, including 
screening laboratory evaluations, will be performed locally prior to the 
leukapheresis procedure. 
o Refer to the protocol-specific MOP for details on the leukapheresis procedure.

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Table 8: Venipuncture Volumes 
1 Inability (e.g., loss of IV access) to collect all baseline samples on Day 1 will not exclude the subject from further participation in this study as long as a minimum of baseline clinical safety 
laboratory evaluations and serum for serological immunogenicity assays are collected. 
2 These blood volumes are not included in the blood volume totals. Blood volume depends upon day of early termination visit. 
3 Only for those subjects consented for leukapheresis. These blood volumes are not included in the blood volume totals. 
4  Visits 09-14 windows should be based off the actual Visit 06 date. 
Procedures 
Screening 
Visit 00, Day -42 to -1 
Enrollment/Baseline 
Visit 01, Day 1 
Visit 02, Day 2 
1 day post Dose 1 
Visit 03, Day 3 
2 days post Dose 1 
Visit 04 
Day 8 +/- 1 day 
Visit 05 
Day 15 +/- 2 days 
Visit 06 
Day 29 +/- 2 days 
Visit 07, Day 30 
1 day post Dose 2 
Visit 08, Day 31 
2 days post Dose 2 
Visit 094 
Day 36 +/- 1 day 
Visit 104 
Day 43 +/- 2 days 
Visit 114 
Day 57 +/- 2 days 
Visit 11Af 
Day 71 -7/+ 21 days 
Visit 124 
Day 119 +/- 7 days 
Visit 134 
Day 209 +/- 7 days 
Final Study Visit 144,5 
Day 394 +/-14 days 
Early Termination Visit 
Total Volume of 
Blood Drawn (mL) 
Vaccination 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Clinical Laboratory 
Evaluations1 
28 
8 
 
 
8 
 
8 
 
 
8 
 
 
 
 
 
 
 
60 
Serum for Serological 
Immunogenicity Assays1 
 
16 
 
 
 
16 
16 
 
 
16 
16 
16 
 
16 
16 
16 
162 
144 
PBMCs for Cellular 
Immunology Assays 
 
80 
 
 
 
40 
16 
 
 
16 
40 
16 
 
40 
40 
 
162 or 
402 
288 
Serum for Secondary Research 
 
16 
 
 
 
8 
8 
 
 
8 
8 
8 
 
8 
8 
8 
82 
80 
Serum for Product Assay 
Development 
 
16 
 
 
 
8 
8 
 
 
8 
8 
8 
 
8 
8 
8 
82 
80 
Leukocytes for Secondary 
Research 
(subset of subjects) 
 
 
 
 
 
 
 
 
 
 
 
 
623 
 
 
 
 
 
Per Visit Blood Volume 
Total (mL) 
28 
136 
 
 
8 
72 
56 
 
 
56 
72 
48 
 
72 
72 
32 
- 
652 
Cumulative Blood Volume 
(mL) (prior 56 days) 
 
164 
 
 
172 
244 
300 
 
 
356 
428 
312 
 
72 
72 
32 
 
 
Running Blood Volume 
Total (mL) 
28 
164 
 
 
172 
244 
300 
 
 
356 
428 
476 
 
548 
620 
652 
- 
 

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5 Subjects who participate in the optional third mRNA-1273 vaccination substudy will exit the Schedule of Activities for the main study between Visit 13 and the close of the 
window for Visit 14 and will not have Visit 14, instead will have Visit 14A and subsequent substudy visits. See Section 12, Appendix A for the Schedule of Activities for the 
optional third mRNA-1273 vaccination substudy. 
 
 

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8.2.1 
Procedures to be Followed in the Event of Abnormal Clinical Laboratory Test 
Values or Abnormal Clinical Findings 
If a physiologic parameter, e.g., vital signs, or clinical laboratory value, is outside of the 
protocol-specified range, then the measurement may be repeated once if, in the judgment of the 
participating site PI or appropriate sub-investigator, the abnormality is the result of an acute, 
short-term, rapidly reversible condition (e.g., stress, anxiety or “white coat syndrome”) or other 
source of error. A physiologic parameter may also be repeated if there is a technical problem 
with the measurement caused by malfunctioning, or an inappropriate measuring device (i.e., 
inappropriate-sized BP cuff). 
All abnormal clinical findings or abnormal clinical laboratory tests values that occur post 
vaccination will be considered AEs. 
8.3 
Adverse Events and Serious Adverse Events 
8.3.1 
Definition of Adverse Event (AE) 
AE means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). An AE can 
therefore be any unfavorable and unintended sign (including an abnormal clinical laboratory 
finding), symptom or disease temporally associated with the use of medicinal (investigational) 
product. 
Any medical condition that is present at the time that the subject is screened will be considered 
as baseline and not reported as an AE. However, if the severity of any pre-existing medical 
condition increases, it should be recorded as an AE. 
AEs can be further divided into solicited AEs and unsolicited AEs. Solicited AEs are those for 
which the study team will specifically query the subject whether they occurred. Unsolicited AEs 
are those events that the subject report occurring without being queried about the specific event. 
All AEs will be assessed for severity and relationship to study intervention (Section 8.3.3). 
Reporting of all AEs, solicited and unsolicited, will occur during the period from study product 
administration on Day 1 through 28 days after the second vaccination. After Day 57 through the 
end of study on Day 394, only SAEs, Protocol Specified AESIs, MAAEs, and NOCMCs will be 
reported as AEs. 
All AEs, solicited and unsolicited, will be captured on the appropriate DCF. Information to be 
collected for AEs includes event description, date of onset, assessment of severity, relationship to 
study product and alternate etiology (assessed only by those with the training and authority to 
make a diagnosis and listed on the Form FDA 1572 as the participating site PI or appropriate 
sub-investigator), date of resolution, seriousness, and outcome. AEs occurring during the study-
collection and reporting period will be documented appropriately regardless of relationship. 
AEs will be followed to resolution or stabilization. 
8.3.1.1 
Solicited Adverse Events 
Solicited AEs are anticipated local and systemic AEs for which consistent collection of 
information is desired. Study clinicians will follow and collect resolution information for any 
reactogenicity symptoms that are not resolved within 7 days. 

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Solicited AEs (i.e., reactogenicity) will be collected using a memory aid and recorded on the 
appropriate DCF from the time of each vaccination through 7 days post each vaccination (Days 
1-8 for the first vaccination, and Days 29-36 for the second vaccination). 
For this study, solicited AEs will be: 
• 
Injection site Pain 
• 
Injection site Erythema 
• 
Injection site Edema/Induration 
• 
Headache 
• 
Fatigue 
• 
Myalgia 
• 
Arthralgia 
• 
Nausea 
• 
Fever 
• 
Chills 
8.3.1.2 
Unsolicited Adverse Events 
All AEs spontaneously reported by the subject and/or in response to an open question from study 
staff or revealed by observation, physical examination or other diagnostic procedures must be 
recorded on the appropriate DCF. 
Unsolicited AEs of all severities will be reported from the time of study product administration 
through Day 57. 
After Day 57, only SAEs (as detailed in Section 8.3.2), Protocol Specified AESIs, MAAEs, and 
NOCMCs will be reported through the end of the study (Day 394). 
8.3.1.3 
Possible Adverse Events Associated with Leukapheresis 
For those subjects consented for leukapheresis, the possible adverse events associated with the 
leukapheresis procedure are: 
• Site of needle placement: pain, bruising and discomfort in the arms. 
• Vasovagal episodes, characterized by transient hypotension, dizziness, nausea, and rarely 
syncope. 
• Temporary decrease (1-2 days) in red blood cell count. 
• Blood loss secondary to machine malfunction. 
• Toxicity-associated anticoagulant resulting in a sour taste in the mouth, mild muscle 
cramps and/or tingling sensation around the mouth, feet or hands. 
The risks of the leukapheresis procedure are minimal and are generally confined to the period of 
the actual study visit itself. In this protocol, AEs that are non-serious will not be routinely 
recorded in the study database. 

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Only SAEs that occur during or within 24 hours after the leukapheresis study visit will be 
recorded in the study database. 
8.3.1.4 
Special Reporting of Adverse Events 
Not Applicable 
8.3.2 
Definition of Serious Adverse Event (SAE) 
An SAE is defined in 21 CFR 312.32 as follows: “An AE or suspected adverse reaction is 
considered serious if, in the view of either the participating site PI or appropriate sub-investigator 
or the sponsor, it results in any of the following outcomes: 
• Death, 
• a life-threatening AE, 
• inpatient hospitalization or prolongation of existing hospitalization, 
• a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, 
• or a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.” 
“Life-threatening” refers to an AE that at occurrence represents an immediate risk of death to a 
subject. An event that may cause death if it occurs in a more severe form is not considered life-
threatening. Similarly, a hospital admission for an elective procedure is not considered an SAE. 
All SAEs, as with any AE, will be assessed for severity and relationship to study intervention. 
All SAEs will be recorded on the appropriate SAE DCF. 
All SAEs will be followed through resolution or stabilization by a study clinician, licensed to 
make medical diagnoses and listed on the Form FDA 1572 as the participating site PI or 
appropriate sub-investigator. 
All SAEs will be reviewed and evaluated by DMID and will be sent to the SMC (for periodic 
review unless related) and IRB/IEC. 
8.3.3 
Suspected Unexpected Serious Adverse Reactions (SUSAR) 
A SUSAR is any SAE where a causal relationship with the study product is at least reasonably 
possible but is not listed in the Investigator’s Brochure (IB), Package Insert, and/or Summary of 
Product Characteristics. 
8.3.4 
Classification of an Adverse Event 

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The determination of seriousness, severity and causality will be made by an on-site investigator 
who is qualified (licensed) to diagnose AE information, provide a medical evaluation of AEs and 
classify AEs based upon medical judgment. This includes, but is not limited to, physicians, 
physician assistants and nurse practitioners. 
8.3.4.1 
Severity of Adverse Events 
All AEs or SAEs will be assessed for severity, according to the toxicity grading scales in the 
FDA “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials”. 
For AEs not included in the protocol-defined grading system, the following guidelines will be 
used to describe severity. 
• Mild (Grade 1): Events that are usually transient and may require only minimal or no 
treatment or therapeutic intervention and generally do not interfere with the subject’s 
usual activities of daily living. 
• Moderate (Grade 2): Events that are usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research subject. 
• Severe (Grade 3): Events interrupt usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. Severe events are 
usually incapacitating. 
AEs characterized as intermittent require documentation of onset and duration of each episode. 
The start and stop date of each reported AE will be recorded on the appropriate DCF. Changes in 
the severity of an AE will be documented to allow an assessment of the duration of the event at 
each level of intensity. 
8.3.4.2 
Relationship to Study Intervention 
For each reported adverse reaction, the participating site PI or qualified designee must assess the 
relationship of the event to the study product using the following guidelines: 
• Related – The AE is known to occur with the study intervention, there is a reasonable 
possibility that the study intervention caused the AE, or there is a temporal relationship 
between the study intervention and event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the study intervention and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study 
intervention and event onset, or an alternate etiology has been established. 
8.3.5 
Time Period and Frequency for Event Assessment and Follow-Up 
For this study: 
• solicited AEs will be collected from Days 1-8 (7 days post first vaccination) and Days 
29-36 (7 days post second vaccination). 
• unsolicited AEs will be collected from Days 1-57. 

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• SAEs, Protocol Specified AESIs, MAAEs, and NOCMCs will be collected from Day 1 
through the end of the study (Day 394). 
8.3.6 
Adverse Event Reporting 
8.3.6.1 
Investigators Reporting of AEs 
Information on all AEs should be recorded on the appropriate DCF. All clearly related signs, 
symptoms and results of diagnostic procedures performed because of an AE should be grouped 
together and recorded as a single diagnosis. If the AE is a clinical laboratory abnormality that is 
part of a clinical condition or syndrome, it should be recorded as the syndrome or diagnosis 
rather than the individual clinical laboratory abnormality. Each AE will also be described in 
terms of duration (start and stop date), severity, association with the study product, action(s) 
taken, and outcome. 
8.3.7 
Serious Adverse Event Reporting 
8.3.7.1 
Investigators Reporting of SAEs 
Any AE that meets a protocol-defined criterion as an SAE must be submitted immediately 
(within 24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group, at 
the following address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 
In addition to the SAE form, select SAE data fields must also be entered into the SDCC system. 
Refer to the protocol-specific MOP for details regarding this procedure. 
Other supporting documentation of the event may be requested by the DMID Pharmacovigilance 
Group and should be provided as soon as possible. The DMID Medical Monitor will review and 
assess the SAE for regulatory reporting and potential impact on study subject safety and protocol 
conduct. 
At any time after completion of the study, if the participating site PI or appropriate sub-
investigator becomes aware of an SAE that is suspected to be related to study product, the 
participating site PI or appropriate sub-investigator will report the event to the DMID 
Pharmacovigilance Group. 
8.3.7.2 
Regulatory Reporting of SAEs 
Following notification from the participating site PI or appropriate sub-investigator, DMID, as 
the IND sponsor, will report any SUSAR in an IND safety report to the FDA and will notify all 
participating site PIs (i.e., all PIs to whom the sponsor is providing drug under its IND(s) or 
under any PI’s IND(s)) of potential serious risks from clinical studies or any other source, as 
soon as possible. DMID will report to the FDA any unexpected fatal or life-threatening 
suspected adverse reaction as soon as possible, but in no case later than 7 calendar days after the 

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sponsor’s initial receipt of the information. If the event is not fatal or life-threatening, the IND 
safety report will be submitted within 15 calendar days after the sponsor determines that the 
information qualifies for reporting as specified in 21 CFR Part 312.32.  Relevant follow-up 
information to an IND safety report will be submitted as soon as the information is available. 
Upon request from FDA, DMID will submit to the FDA any additional data or information that 
the agency deems necessary, as soon as possible, but in no case later than 15 calendar days after 
receiving the request. 
SAEs that are not SUSARs will be reported to the FDA at least annually in a summary format 
which includes all SAEs. 
8.3.8 
Reporting Events to Subjects 
Subjects will be informed of any AEs or SAEs that occur as part of their participation in this 
trial. 
8.3.9 
Adverse Events of Special Interest (AESIs) 
Adverse Events of Special Interest (AESIs) represent any events for which additional data 
(besides the standard AE data) are desired. These may be at the request of the regulatory agency, 
industry partner or DMID, and driven by a regulatory requirement, or known or potential risk 
from the product or class. Non-structured data similar to SAEs will be collected for AESIs. 
AESIs encompass the following terms: 
• Protocol Specified AESIs:  
o All suspected cases of myocarditis or pericarditis should be recorded. For 
reporting purposes, a subject who displays signs/symptoms consistent with 
myocarditis or pericarditis should be reported as a potential case of myocarditis or 
pericarditis. 
• NOCMCs – defined as any new ICD diagnosis (per current International Statistical 
Classification of Diseases and Related Health Problems) that is applied to the subject 
during the course of the study, after receipt of the study agent, that is expected to 
continue for at least 3 months and requires continued health care intervention. 
• MAAEs – defined as hospitalization, an emergency room visit or an otherwise 
unscheduled visit to or from medical personnel for any reason. 
All AESIs are assessed, recorded, and followed as described above under AEs. AESIs that meet 
SAE criteria will be reported on an SAE form within 24 hours to the DMID Pharmacovigilance 
Group, at the following address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 

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In addition, for documentation and medical assessment purposes AESIs that do not meet SAE 
criteria will also be reported on an SAE form within the period for AE reporting to the DMID 
Pharmacovigilance Group; however, the narrative will indicate that the AESI did not meet SAE 
criteria. 
8.3.10 
Reporting of Pregnancy 
Pregnancy is not an AE. However, any pregnancy that occurs during study participation (through 
Day 394) should be reported to the sponsor on the appropriate DCF. Pregnancy should be 
followed to outcome. 
8.4 
Unanticipated Problems 
8.4.1 
Definition of Unanticipated Problems (UPs) 
The Department of Health and Human Services (DHHS) OHRP considers unanticipated 
problems involving risks to subjects or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
▪ Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the subject 
population being studied; 
▪ Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
▪ Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
8.4.2 
Unanticipated Problem Reporting 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
▪ UPs that are SAEs will be reported to the IRB and to the SDCC/study sponsor within 24 
hours of the participating site PI or appropriate sub-investigator becoming aware of the 
event per the above described SAE reporting process. 
▪ UPs that are SAEs will be collected from Day 1 through the end of the study (Day 394). 
▪ Any other UP will be reported to the IRB and to the SDCC/study sponsor within 3 days 
of the participating site PI or appropriate sub-investigator becoming aware of the 
problem. 
▪ UPs that are not SAEs will be collected from Days 1-57. 
8.4.3 
Reporting Unanticipated Problems to Subjects 
Subjects will be informed of any UPs that occur as part of their participation in this trial. 

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9. 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
This is a phase I, open-label, dose-ranging clinical trial and is not designed to test a specific 
hypothesis. Rather, it is intended to obtain preliminary estimates in healthy adults of the safety, 
reactogenicity, and immunogenicity of mRNA-1273. 
9.2 
Sample Size Determination 
Rare AEs are not demonstrable in a clinical study of this size; however, the probabilities of 
observing one or more AEs given various true event rates are presented in Table 9. With the 
assumption that all enrolled subjects will likely complete immunizations and safety visits in this 
relatively short duration study, the following statistical considerations apply. With 15 subjects in 
each dose group (cohorts 1-3,10,13), the chance of observing at least one AE of probability 20% 
or more is approximately 97%. Therefore, if no AEs of a given type occur in a dose group 
(cohorts 1-3,10,13), we can be relatively confident that they will occur in fewer than 20% of 
people once the vaccine is implemented. With 60 subjects across these four dosing cohorts (1-
3,10), the chance of observing at least one AE of probability 5% or more is at least 95%. 
Therefore, if no AEs of a given type occur across the combined doses, we can be very confident 
that any dosage-independent event will occur in fewer than 5% of people once the vaccine is 
implemented. If Cohort 13 is enrolled and there are 75 subjects across five dosing cohorts (1-
3,10,13), the chance of observing at least one AE of probability 5% or more is at least 97.9%. 
Therefore, if no AEs of a given type occur across the combined doses, we can be very confident 
that any dosage-independent event will occur in fewer than 5% of people once the vaccine is 
implemented. With 10 subjects in each dose group (cohorts 4-9,11-12), the chance of observing 
at least one AE of probability 20% or more is approximately 89.3%. Therefore, if no AEs of a 
given type occur in a dose group (cohorts 4-9,11-12), we can be relatively confident that they 
will occur in fewer than 20% of people once the vaccine is implemented in the older population. 
With 30 subjects across each of the two older subject dosing cohorts (i.e., cohorts 4,5,11 and 
7,8,12), the chance of observing at least one AE of probability 5% or more is at least 78.5%. 
Therefore, if no AEs of a given type occur across the combined doses, we can be very confident 
that any dosage-independent event will occur in fewer than 5% of older people once the vaccine 
is implemented. If Cohorts 6 and 9 are enrolled and there are 40 subjects across each of the two 
older subject dosing cohorts (i.e., cohorts 4,5,6,11 and 7,8,9,12), the chance of observing at least 
one AE of probability 5% or more is at least 87.1%. Therefore, if no AEs of a given type occur 
across the combined doses, we can be very confident that any dosage-independent event will 
occur in fewer than 5% of older people once the vaccine is implemented. 
Table 9: Probability of Observing an Adverse Event for Various Event Rates 
N 
“True” 
Event 
Rate 
Probability of 
Observation 
(%) 
N 
“True” 
Event 
Rate 
Probability of 
Observation 
(%) 
N 
“True” 
Event 
Rate 
Probability 
of 
Observation 
(%) 
15 
0.1% 
1.5 
60 
0.1% 
5.8 
75 
0.1% 
7.2 
0.5% 
7.2 
0.5% 
26.0 
0.5% 
31.3 
1.0% 
14.0 
1.0% 
45.3 
1.0% 
52.9 

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N 
“True” 
Event 
Rate 
Probability of 
Observation 
(%) 
N 
“True” 
Event 
Rate 
Probability of 
Observation 
(%) 
N 
“True” 
Event 
Rate 
Probability 
of 
Observation 
(%) 
2.0% 
26.1 
2.0% 
70.2 
2.0% 
78.0 
3.0% 
36.7 
3.0% 
83.9 
3.0% 
89.8 
4.0% 
45.8 
4.0% 
91.4 
4.0% 
95.3 
5.0% 
53.7 
5.0% 
95.4 
5.0% 
97.9 
10.0% 
79.4 
10.0% 
99.8 
10.0% 
>99.9 
15.0% 
91.3 
15.0% 
>99.9 
15.0% 
>99.9 
20.0% 
96.5 
20.0% 
>99.9 
20.0% 
>99.9 
 
N 
“True” 
Event 
Rate 
Probability of 
Observation 
(%) 
N 
“True” 
Event 
Rate 
Probability of 
Observation 
(%) 
N 
“True” 
Event 
Rate 
Probability 
of 
Observation 
(%) 
10 
0.1% 
1.0 
30 
0.1% 
3.0 
40 
0.1% 
3.9 
0.5% 
4.9 
0.5% 
14.0 
0.5% 
18.2 
1.0% 
9.6 
1.0% 
26.0 
1.0% 
33.1 
2.0% 
18.3 
2.0% 
45.5 
2.0% 
55.4 
3.0% 
26.3 
3.0% 
59.9 
3.0% 
70.4 
4.0% 
33.5 
4.0% 
70.6 
4.0% 
80.5 
5.0% 
40.1 
5.0% 
78.5 
5.0% 
87.1 
10.0% 
65.1 
10.0% 
95.8 
10.0% 
98.5 
15.0% 
80.3 
15.0% 
99.2 
15.0% 
99.8 
20.0% 
89.3 
20.0% 
99.9 
20.0% 
>99.9 
9.3 
Populations for Analyses 
The Safety Analysis population for the main study includes all subjects who received one dose of 
vaccine. Analyses for the primary safety population will include safety reported through the end 
of the main study. A modified primary safety population analysis will also be performed that 
excludes safety data collected after subjects receive either the third mRNA-1273 vaccination in 
the optional substudy or non-study EUA vaccine, if applicable. 
The modified intent-to-treat (mITT) population includes all subjects who received one dose of 
vaccine and contributed both pre- and at least one post-vaccination venous blood samples for 
immunogenicity testing for which valid results were reported. 
In the final analysis, protocol deviations will be reviewed to determine which protocol deviations 
may affect the analysis. The per protocol (PP) population will then be defined – and this includes 
all subjects in the mITT subset with the following exclusions: 
• 
Data from all available visits for subjects found to be ineligible at baseline. 
• 
Data from all visits subsequent for the protocol deviations that are considered to affect 
the science. 

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• 
Data from any visit that occurs substantially out of window. 
9.4 
Statistical Analyses 
Interim analyses of safety, reactogenicity, and immunologic response data may be done, as 
needed. 
The final analysis will be performed after the final data lock (through Day 394) and clinical 
study report (CSR) completed when all primary safety endpoint data and all secondary 
immunogenicity endpoint data are available and received by the SDCC. Any available data from 
the exploratory immunogenicity endpoints may also be included in the CSR. Remaining 
exploratory immunogenicity endpoint data may be included in an addendum to the CSR, 
publication of manuscript(s), or other report(s). Abbreviated analysis plans that describe planned 
analyses to facilitate dissemination of study data for public health reasons, including manuscript 
publication(s), will be developed by the SDCC. A full statistical analysis plan (SAP) will be 
developed by the SDCC and finalized prior to the primary data lock. 
9.4.1 
General Approach 
Unless otherwise noted in the SAP, continuous variables will be summarized using the following 
descriptive statistics: n (non-missing sample size), mean, standard deviation, median, maximum 
and minimum. The frequency and percentages (based on the non-missing sample size) of 
observed levels will be reported for all categorical measures. 
9.4.2 
Analysis of the Primary Endpoint(s) 
Section 9.4.4 describes the analyses of Safety which is the primary endpoint of this protocol. 
9.4.3 
Analysis of the Secondary Endpoint(s) 
Summaries and analysis of immunogenicity data will be presented for the mITT population. If 
there are protocol deviations which may affect the analysis, a per-protocol (PP) analysis may 
also be performed. 
Seroconversion is defined as a 4-fold increase in antibody titer over baseline. 
Seroconversion rates, GMFR and GMT for SARS-CoV-2 as measured by IgG ELISA will be 
calculated at Days 1 (GMT only) and 57 by cohort and will be summarized graphically. 
Seroconversion rates, GMFR and GMT will be presented with their corresponding 95% 
confidence interval (CI) estimates at each timepoint and overall peak GMT, and the pair-wise 
differences between seroconversion rates by cohort will be summarized by study day along with 
95% CIs. 
9.4.4 
Safety Analyses 
Summaries and analysis of safety data will be presented for the Safety Analysis Population. 
Solicited AEs will be summarized by severity for each day post vaccination (Days 1-8) and as 
the maximum severity over all 8 days. Additionally, solicited AEs will be analyzed by taking the 
most severe response over the follow-up period, dichotomizing into a binary variable (none 
versus mild, moderate, or severe) and using standard techniques, such as exact confidence 

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intervals (CI), to summarize the proportion of subjects reporting each symptom, any application 
site symptom, and any systemic symptom. 
Unsolicited non-serious AEs will be collected from the time of first vaccination through 28 days 
after the second vaccination. Unsolicited AEs will be coded by MedDRA for preferred term and 
system organ class (SOC). SAEs, Protocol Specified AESIs, MAAEs, and NOCMCs will be 
collected from the time of first vaccination through the end of the study (Day 394). The numbers 
of SAEs and MAAEs will be reported by detailed listings showing the event description, 
MedDRA preferred term and SOC, relevant dates (vaccinations and AEs), severity, relatedness, 
and outcome for each event. Non-serious unsolicited AEs will be summarized as number and 
percentage of subjects reporting at least one event in each MedDRA preferred term and SOC, 
cross tabulated by severity and relationship to study product. Additionally, the proportion of 
subjects and exact 95% CIs of AEs in aggregate and by MedDRA categories will be computed. 
Clinical laboratory data will be summarized by severity for each visit, and as the maximum over 
all post-vaccination visits. Graphical presentations may include box plots and shift plots. 
9.4.5 
Baseline Descriptive Statistics 
Summaries of demographic variables such as age, sex, ethnicity, and race will be presented by 
cohort and overall. Summaries of baseline clinical laboratory values will be presented by cohort 
and overall. 
9.4.6 
Planned Interim and Early Analyses 
Data may be disseminated to public health officials and partners as needed and included in 
publications and presentations to inform the global scientific community. Early analyses will 
include safety and immunogenicity as described in Sections 9.4.6.1, 9.4.6.2 and 9.4.6.3. Further, 
the protocol team will review data periodically to confirm no halting criteria have been met as 
described in Section 10.1.6.1. 
Cumulative safety information, study status, and primary endpoint results may be published, 
presented at a public forum, or presented as summaries aggregated by study arm at the discretion 
of the sponsor while the main study is ongoing. Any ad-hoc analyses, jointly developed by the 
SDCC and/or the VRC, other participating laboratories and ModernaTX, Inc., will be executed 
by the SDCC as needed. None of the interim analyses will include any formal statistical 
hypothesis testing; therefore, p value adjustment will not be made to any analyses. 
9.4.6.1 
Interim Safety Analyses 
Given the need for rapid review and dissemination of study data for public health reasons, AEs 
and SAEs maybe reviewed as necessary outside of SMC reviews. The SMC will not need to 
meet (unless halting rules are met), and materials will be provided electronically. Documentation 
of review and any concerns noted will be solicited electronically. 
The SMC will review cumulative AE data after all subjects in cohorts 1 and 2 have completed 
Day 8. In addition, cumulative AE data will be provided to the SMC after all subjects in cohorts 
3, 4, 5, 7, and 8 have completed Day 8. Cumulative AE data will also be provided to the SMC 
after all subjects in all cohorts have completed Day 57. Documentation of review and any 
concerns noted will be solicited electronically. 

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9.4.6.2 
Interim Immunogenicity Review 
For public health reasons there will be several immunogenicity reviews. The following reviews 
are anticipated once data are available: 
• Sentinel subjects in cohorts 1 and 2, ELISA IgG data through Day 29; 
• All subjects in cohorts 1 and 2, ELISA IgG data through Day 29; 
• Sentinel subjects in cohort 3, ELISA IgG data through Day 29; 
• All subjects in cohort 3, ELISA IgG data through Day 29; 
• All subjects in cohorts 4, 5, 7 and 8, ELISA IgG data through Day 29; 
• All subjects in cohorts 10-12, ELISA IgG data through Day 29; 
• All subjects in cohort 13, ELISA IgG data through Day 29 (if cohort is enrolled); 
• All subjects in cohorts 6 and 9, ELISA IgG data through Day 29 (if cohorts are enrolled); 
• Sentinel subjects in cohorts 1 and 2, ELISA IgG data through Day 57; 
• All subjects in cohorts 1 and 2, ELISA IgG data through Day 57; 
• Sentinel subjects in cohort 3, ELISA IgG data through Day 57; 
• All subjects in cohort 3, ELISA IgG data through Day 57; 
• All subjects in cohorts 4, 5, 7 and 8, ELISA IgG data through Day 57; 
• All subjects in cohorts 10-12, ELISA IgG data through Day 57; 
• All subjects in cohort 13, ELISA IgG data through Day 57 (if cohort is enrolled) 
• All subjects in cohorts 6 and 9, ELISA IgG data through Day 57 (if cohorts are enrolled). 
• Additional data review of immunogenicity may be performed to inform public health 
decisions. 
Data may be disseminated to public health officials and partners as needed and included in 
publications and presentations to inform the global scientific community. 
9.4.6.3 
Interim Immunogenicity and Safety Review 
Interim analyses of safety, reactogenicity, and immunologic response data may be done, as 
needed. 
9.4.7 
Sub-Group Analyses 
The protocol does not define any formal subgroup analyses, and the study is not adequately 
powered to perform subgroup analyses. 
9.4.8 
Tabulation of Individual Subject Data 
In general, all data will be listed, sorted by cohort and subject, and when appropriate by visit 
number within subject. 

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9.4.9 
Exploratory Analyses 
Summaries and analysis of immunogenicity data will be presented for the mITT population. If 
there are protocol deviations which may affect the analysis, a PP analysis may also be 
performed. 
Seroconversion is defined as a 4-fold increase in antibody titer over baseline. 
Seroconversion rates, GMFR and GMT for SARS-CoV-2 as measured by IgG, IgA and IgM 
ELISA, neutralization assay using SARS-CoV-2 pseudovirus and neutralization assay using a 
live wild-type SARS-CoV-2 will be calculated for specified timepoints by cohort and will be 
summarized graphically. Seroconversion rates, GMFR and GMT will be presented with their 
corresponding 95% CI estimates at each timepoint and overall peak GMT, and the pair-wise 
differences between seroconversion rates by cohort will be summarized by study day along with 
95% CI. 
Summaries and analysis of cellular assay data will be presented for the mITT population. If there 
are protocol deviations which may affect the analysis, a PP analysis may also be performed. 
The magnitude, phenotype and percentage of cytokine producing S protein-specific T cells will 
be summarized at each timepoint by vaccination group. 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Regulatory, Ethical, and Study Oversight Considerations 
This study will be conducted in conformity with the principles set forth in The Belmont Report: 
Ethical Principles and Guidelines for the Protection of Human Subjects of Research (US 
National Commission for the Protection of Human Subjects of Biomedical and Behavioral 
Research; April 18, 1979), and the federal policy for the Protection of Human Subjects codified 
in 45 CFR Part 46, 21 CFR Part 50 (Protection of Human Subjects), and the ICH E6(R2). 
An OHRP-registered IRB will review and approve this protocol, associated informed consent 
documents, recruitment materials, and handouts or surveys intended for the subjects, prior to the 
recruitment, screening and enrollment of subjects. The IRB review shall be in accordance with 
45 CFR 46 and 21 CFR 50, 21 CFR 56 (IRBs), and other federal, state, and local regulations and 
policies, as applicable. 
Each institution engaged in this research will hold an OHRP-approved FWA. 
Any amendments to the protocol or informed consent documents will be approved by the IRB 
before they are implemented. IRB review and approval will occur at least annually throughout 
the duration of the study. The participating site PI will notify the IRB of deviations from the 
protocol and reportable SAEs, as applicable to the IRB policy. 
DMID must receive the documentation that verifies IRB approval for this protocol, informed 
consent documents and associated documents, prior to the recruitment, screening and enrollment 
of subjects, and any IRB approvals for continuing review or amendments as required by the 
DMID. 
10.1.1 
Informed Consent Process 

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Informed consent is a process that is initiated prior to an individual agreeing to participate in a 
trial and continuing throughout the individual’s trial participation. Investigators or designated 
research staff will obtain a subject’s informed consent in accordance with the requirements of 45 
CFR 46, 21 CFR 50 and 21 CFR 56 for FDA-regulated studies, state and local regulations and 
policy, and ICH E6 GCP before any study procedures or data collection are performed. The 
participating site PI or other study staff may obtain oral or written information for the purpose of 
screening, recruiting, or determining the eligibility of prospective subjects without the informed 
consent of the prospective subject if the process is approved by the IRB. 
At the first study visit, informed consent will be obtained and documented before any study 
procedures are performed. Subjects will receive a concise and focused presentation of key 
information about the clinical trial, verbally and with a written consent form. The key 
information about the purpose of the study, the procedures and experimental aspects of the study, 
study interventions/products, risks and discomforts, the expected duration of the subject’s 
participation in the trial, any expected benefits to the subject, and alternative treatments and 
procedures that may be available to the subject. The explanation will be organized and presented 
in lay terminology and language that facilitates understanding why one might or might not want 
to participate. 
Subjects will receive an explanation as to whether any compensation and any medical treatments 
are available if injury occurs, and, if so, what they consist of, or where further information may 
be obtained. Subjects will be informed of the anticipated financial expenses, if any, to the subject 
for participating in the trial, as well as any anticipated prorated payments, if any, to the subject 
for participating in the trial. They will be informed of whom to contact (e.g., the participating site 
PI) for answers to any questions relating to the research project. Information will also include the 
foreseeable circumstances and/or reasons under which the subject’s participation in the trial may 
be terminated. The subjects will be informed that participation is voluntary and that they are free 
to withdraw from the study for any reason at any time without penalty or loss of benefits to 
which the subject is otherwise entitled. Subjects will be allowed sufficient time to consider 
participation in this research trial and have the opportunity to discuss this trial with their family, 
friends or legally authorized representative, or think about it prior to agreeing to participate. 
Subjects will be informed that records identifying the subject will be kept confidential, and, to 
the extent permitted by the applicable laws and/or regulations, will not be made publicly 
available. If the results of the trial are published, the subject’s identity will remain confidential. 
Subjects will be informed, even if identifiers are removed, that information collected from this 
research and/or specimens may be used for secondary research, including the sharing of 
deidentified data. 
Subjects will be informed that the monitor(s), auditors(s), IRB, NIAID, and regulatory 
authority(ies) will be granted direct access to the subject’s original medical records for 
verification of clinical trial procedures and/or data without violating the confidentiality of the 
subject, to the extent permitted by the applicable laws and regulations, and that, by signing a 
written ICF, the subject is authorizing such access. 
ICFs will be IRB-approved, and subjects will be asked to read and review the consent form. 
Subjects must sign the ICF prior to starting any study procedures being done specifically for this 
trial. Once signed, a copy of the ICF will be given to the subject for their records. 

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New information will be communicated by the participating site PI to subjects who consent to 
participate in this trial in accordance with IRB requirements. The informed consent document 
will be updated, and subjects will be re-consented per IRB requirements, if necessary. 
10.1.1.1 
Requirements for Permission by Parents/Guardians and Assent by Children (in 
case of a minor) 
Not Applicable 
10.1.1.2 
Other Informed Consent Procedures 
The rights and privacy of human subjects who participate in genomic or phenotypic research 
studies will be protected at all times. The consent process, including relevant language in the 
ICF, will provide an explanation of the potential risks to the individual study subjects and their 
families. Clinical metadata, genomic, or other datasets or a subset of the clinical and other 
metadata that may potentially identify human subjects will not be released in unrestricted 
databases. Subjects will be informed that the evolution of genomic technology and analytical 
methods raises the risk of re-identification, even when specimens are de-identified. 
Subjects will be asked for consent to collect additional blood, the use of residual specimens, and 
the sharing of genetic information and samples for secondary research. This extra/residual blood 
and corresponding serum, plasma and PBMCs will be used as back-up specimens for PP defined 
assays or designated for secondary research use and stored indefinitely at a designated storage 
facility. 
Subjects will be asked to consent specifically to genetic testing, including DNA sequencing. 
DNA sequencing data will be kept private. DNA data may be used to produce commercial 
antibody-based therapeutics. Subjects will not share in profits or commercial rights to those 
products. 
To support development of diagnostics, therapeutics and vaccines, a subset of subjects enrolled 
in cohorts 2, 3, 5, 10, and 11, and possibly cohort 6, if enrolled, will also be asked to consent for 
leukapheresis to collect additional samples for secondary research, which will be stored 
indefinitely at a designated storage facility. 
If subjects choose not to provide permission for extra blood and secondary research use, they 
will not be eligible for enrollment into the study. However, consent for leukapheresis is not 
required for study participation. 
Collection of extra/residual samples during the course of the study will help facilitate rapid 
follow-on analyses, if warranted, to provide more comprehensive scientific insights into the 
impact (safety and immunological) of the vaccine on the host response to vaccination. To 
maintain statistical power in follow-on analyses it is important that extra blood collection and 
secondary research use be included in as many subjects as possible, due to the limited sample 
size per treatment arm, with the exception of leukapheresis. 
The stored samples will be labeled with barcodes to maintain confidentiality. Research with 
identifiable samples and data may occur as needed, however, subject confidentiality will be 
maintained as described for this protocol and with IRB approval. 

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Samples designated for secondary research use may be used for additional immunological 
assessments that may include but are not limited to antibody epitope mapping, B and T cell 
repertoire determination, non-traditional immune assay development, determination of innate 
immune factors and the ability of vaccine-induced antibodies to cross-react to different proteins 
and virus strains. These blood samples might be used in new or different immunological 
laboratory tests, to provide information for the development of new vaccines or therapeutics, or 
for the studies of nCoV or other infections. Secondary research using DNA may also be 
warranted to understand genetic factors involved in vaccination failures. 
Samples will not be sold for commercial profit. Although the results of any future research may 
be patentable or have commercial profit, subjects will have no legal or financial interest in any 
commercial development resulting from any future research. 
There are no direct benefits to the subject for extra specimens collected or from the secondary 
research. No results from secondary research will be entered into the subject’s medical record.  
Incidental findings will not be shared with the subject, including medically actionable incidental 
findings, unless required by law. 
Risks are associated with the additional volume of blood collected, such as anemia. Risks for 
loss of privacy and confidentiality are described below. 
Subjects may withdraw permission to use samples for secondary use at any time. They will need 
to contact the participating site and the samples will be removed from the study repository after 
this study is completed and documentation will be completed that outlines the reason for 
withdrawal of permission for secondary use of samples. Subjects who withdraw consent before 
the last visit will not have the extra blood drawn for secondary use. 
Human Genetic Testing 
The research staff will seek the subjects’ consent for extra and residual specimens to be stored 
and used for secondary research, including genetic research, evaluating human genomic and 
phenotypic markers. The rights and privacy of human subjects who participate in genomic or 
phenotypic research studies will be protected at all times. 
The consent process will include an explanation of the potential risks to the individual subjects 
and their families associated with data submitted to an NIH data repository and subsequent 
sharing. Data that may potentially identify human subjects will not be released in unrestricted 
databases. Subjects will be informed that the evolution of genomic technology and analytical 
methods raises the risk of re-identification, even when specimens are de-identified. The consent 
will include whether individual subject data will be shared through a NIH controlled access data 
repository. Data for genomic or phenotypic research will be submitted to a controlled access data 
repository, therefore, informed consent permitting the data sharing must be documented, even if 
the specimens are de-identified. 
10.1.2 
Study Termination and Closure 
In Section 7, Study Intervention Discontinuation and Subject Discontinuation/Withdrawal, 
describes the temporary halting of the study. 
This study may be prematurely terminated if there is sufficient reasonable cause, including, but 
not limited to: 

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• Determination of unexpected, significant, or unacceptable risk to subjects 
• Results of interim analysis 
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or not evaluable 
• Regulatory authorities 
If the study is prematurely terminated, the PI will promptly inform study subjects and the IRB as 
applicable. Study subjects will be contacted, as applicable, and be informed of changes to study 
visit schedule. The PI will assure appropriate follow-up for the subjects, as necessary. 
The sponsor will notify regulatory authorities as applicable. 
10.1.3 
Confidentiality and Privacy 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and 
the sponsor(s) and their agents. This confidentiality is extended to cover clinical information 
relating to subjects, test results of biological samples and genetic tests, and all other information 
generated during participation in the study. No identifiable information concerning subjects in 
the study will be released to any unauthorized third party. Subject confidentiality will be 
maintained when study results are published or discussed in conferences. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB, 
and/or regulatory agencies may inspect all documents and records required to be maintained by 
the participating site PI, including, but not limited to, medical records (office, clinic, or hospital) 
and pharmacy records for the subjects in this study. The participating site will permit access to 
such records. 
All source records, including electronic data, will be stored in secured systems in accordance 
with institutional policies and federal regulations. 
All study data and research specimens that leave the participating site (including any electronic 
transmission of data) will be identified only by a coded number that is linked to a subject through 
a code key maintained at the participating site. Names or readily identifying information will not 
be released unless DMID approves and it aligns with the consent form, or according to laws for 
required reporting. 
Because it may be possible to re-identify de-identified genomic data, even if access to data is 
controlled and data security standards are met, confidentiality cannot be guaranteed, and re-
identified data could potentially be used to discriminate against or stigmatize subjects, their 
families, or groups. In addition, there may be unknown risks. 
As this research is funded by the NIH, it is covered by NIH policy which effectively issues the 
research a Certificate of Confidentiality (COC). By this policy, researchers cannot be forced to 
disclose or provide, in any Federal, State, or local civil, criminal, administrative, legislative, or 
other proceeding, the name of such individual or any such information, document, or 
biospecimen that contains identifiable, sensitive information about the individual and that was 
created or compiled for purposes of the research, unless such disclosure or use is made with the 
consent of the individual to whom the information, document, or biospecimen pertains. 

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The Certificate cannot be used to resist a demand for information from personnel of the United 
States Government that is used for auditing or evaluation of federally funded projects, like this 
study, or for information that must be released in order to meet the requirements of the FDA. 
A COC does not prevent subjects from voluntarily releasing information about themselves or 
their involvement in this research. If any person or agency obtains a written consent to receive 
research information, then the researchers may not use the Certificate to withhold that 
information. 
The COC does not prevent the researchers from reporting, without the subject’s consent, 
information that would identify the subject as a subject in the research project in the case of 
matters that must be legally reported, including child and elder abuse, sexual abuse, or wanting 
to harm themselves or others. 
The release of individual private information or specimens for other research will only occur if 
consent was obtained from the individual to whom the information, document, or biospecimen 
pertains, or that the release is in compliance with applicable Federal regulations governing the 
protection of human subjects in research. 
10.1.4 
Secondary Use of Stored Specimens and Data 
Secondary Human Subject Research is the re-use of identifiable data or identifiable 
biospecimens that were collected from some other ‘‘primary’’ or ‘‘initial’’ activity, such as the 
data and samples collected in this protocol. This section will detail the samples and data 
available for secondary research. Any use of the sample or data, however, will be presented in a 
separate protocol and require separate IRB approval. 
10.1.4.1 
Samples for Secondary Research 
The following types of samples will be stored and used for secondary research: 
• Residual Research Sample: Any leftover Primary Research Sample after the laboratory 
testing specified in this protocol is completed will be stored for future studies with the 
subject’s consent. 
• Repository Research Sample: Samples will be collected with the subject’s consent in this 
protocol with the intent to store for additional research (i.e., samples collected beyond 
those needed for primary research) and will be used in future studies. Amendments to this 
protocol with additional assays may use repository research samples. 
Samples will be stored indefinitely at a DMID-designated storage facility. Each sample will be 
encoded (labeled) only with a barcode and a unique tracking number to protect subject 
confidentiality. Secondary research with coded samples and data may occur, however, subject 
confidentiality will be maintained as described for this protocol. An IRB review of the secondary 
research using coded specimens is required. 
Residual/Repository Research Samples, upon written request and approval from DMID and any 
approvals required by the site or network, may be shared for secondary research with 
investigators at the participating site, with researchers at other Infectious Disease Clinical 
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laboratories. The samples will not be sold or used directly for production of any commercial 
product. DMID will authorize shipment from the DMID CMS. 
Reports from secondary research will not be kept in the subjects’ health records or shared with 
subjects, unless required by law. Reports will not be sent to the specimen repository. 
The subject’s decision can be changed at any time by notifying the study doctors or nurses in 
writing. To participate in this study, subjects must consent for storage of samples for secondary 
use. If the subject subsequently changes his/her decision, the samples will be destroyed if the 
samples have not been used for research or released for a specific research project. 
10.1.4.2 
Data Sharing for Secondary Research 
Data from this study may be used for secondary research. All of the individual subject data 
collected during this study will be made available after de-identification. The SAP and Analytic 
Code will also be made available. Data will be available immediately following publication, with 
no end date. Upon written request, with provision of a methodologically sound proposal, and 
approval from DMID and any approvals required by the site or network, data may be shared for 
secondary research with investigators/researchers. The data will be available for only the purpose 
outlined in the approved proposal. 
For access to genomic data in the NIH designated controlled access database, an investigator (or 
data requestor) must submit a Data Access Request which certifies adherence to the NIH 
Security Best Practices for Controlled-Access data subject to the NIH Genomic Data Sharing 
(GDS) Policy. 
The participating site PI may request removal of data on individual study subjects from NIH data 
repositories in the event that a research subject withdraws or changes his or her consent. 
However, some data that have been distributed for approved research use cannot be retrieved. 
10.1.5 
Key Roles and Study Governance 
This study is sponsored by DMID. Decisions related to this study will be made by the protocol 
team, which includes representatives from the participating site (PI), DMID (sponsor), VRC, and 
ModernaTX, Inc. Key Roles are noted in the protocol-specific MOP. 
10.1.6 
Safety Oversight 
10.1.6.1 
Protocol Team Oversight 
The protocol team will meet at the following timepoints to review AE data and to ensure no 
halting rules have been met: 
• after the four 25 mcg (cohort 1) and the four 100 mcg (cohort 2) sentinel subjects have 
completed Day 5. 
• after the full cohorts 1 and 2 have completed Day 8. 
• after the four 250 mcg (cohort 3) sentinel subjects have completed Day 5. 
• after the full cohorts 1 and 2 have completed Day 29 (prior to beginning Dose 2 
vaccinations in cohort 3). 
• after the full cohort 3 has completed Day 8. 

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• after the full cohorts 4 and 5 have completed Day 8. 
• after the full cohorts 7 and 8 have completed Day 8. 
• after the full cohort 6, if enrolled, has completed Day 8. 
10.1.6.2 
Safety Monitoring Committee (SMC) 
The SMC is an independent group of at least 2-3 experts that monitors subject safety and advises 
DMID. SMC members will be separate and independent of study staff participating in this trial 
and should not have scientific, financial, or other conflicts of interest related to this trial. The 
SMC will consist of members with appropriate expertise to contribute to the interpretation of 
data from this trial. A quorum will consist of a simple majority. 
The SMC will hold an organizational meeting prior to enrollment. At this meeting, the SMC will 
review the charter, protocol, ICF, IB, and safety report templates. 
Given the frequency and urgency to review data, the SMC will not need to meet (unless halting 
rules are met), and materials will be provided electronically. Documentation of review and any 
concerns noted will be solicited electronically. 
The SMC will review cumulative AE data after all subjects in cohorts 1 and 2 have completed 
Day 8. In addition, cumulative AE data will be provided to the SMC after all subjects in cohorts 
3, 4, 5, 7, and 8 have completed Day 8. Cumulative AE data will also be provided to the SMC 
after all subjects in all cohorts have completed Day 57. Documentation of review and any 
concerns noted will be solicited electronically. 
The SMC does not need to meet for dose escalation to 250 mcg (cohorts 3, 6 and 9) or for 
initiation of the optional third mRNA-1273 vaccination substudy. 
The SMC will meet when trial or optional third mRNA-1273 vaccination substudy halting 
criteria are met, or as requested by the sponsor or PI. 
Ad hoc reviews will occur when trial halting criteria are met, or as requested by the sponsor or 
PI. 
The SMC will have a final review meeting at the end of the trial, defined as the end of the 
optional third mRNA-1273 vaccination substudy. 
Procedures for SMC reviews/meetings will be defined in the SMC charter. The SMC will review 
applicable data, including, but not limited to, enrollment, demographics, dosing data, clinical 
laboratory data, and safety data, at scheduled timepoints during this trial as defined in the SMC 
charter. 
Additional data may be requested by the SMC, and interim statistical reports may be generated 
as deemed necessary and appropriate by DMID. As an outcome of each review/meeting, the 
SMC will make a recommendation as to the advisability of proceeding with study product 
administration, and to continue, modify, or terminate this trial. 
10.1.7 
Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial subjects are 
protected, that the reported trial data are accurate, complete, and verifiable. Clinical Monitoring 
also ensures conduct of the trial is in compliance with the currently approved protocol/ 

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amendment(s), ICH, GCP, and with applicable regulatory requirement(s) and sponsor 
requirements. Clinical monitoring will also verify that any critical study procedures are 
completed following specific instructions in the protocol-specific MOP. 
Monitoring for this study will be performed by DMID. Details of clinical site monitoring are 
documented in a CMP. The CMP describes in detail who will conduct the monitoring, at what 
frequency monitoring will be done, at what level of detail monitoring will be performed, and the 
distribution of monitoring reports. Monitoring visits will include, but are not limited to, review 
of regulatory files, accountability records, electronic case report forms (eCRFs), ICFs, medical 
and laboratory reports, site study intervention storage records, training records, and protocol and 
GCP compliance. Site monitors will have access to each participating site, study staff and all 
study documentation according to the DMID-approved CMP. Study monitors will meet with all 
participating site PIs to discuss any problems and outstanding issues and will document site visit 
findings and discussions. 
10.1.8 
Quality Control (QC) and Quality Assurance (QA) 
To ensure the reliability of study data, the participating site will develop a Clinical Quality 
Management Plan (CQMP). The CQMP will describe: 
• routine internal quality control (QC) and QA activities 
o for the purposes of measuring, documenting and reporting study conduct, protocol 
adherence, human subjects’ protections, and reliability of the protocol-driven data 
collected; 
o independent of sponsor site monitoring. 
• a process for addressing data quality issues (i.e., collecting, recording), and reporting 
findings in a timely manner); systemic issues (i.e., protocol conduct, non-compliance, 
human subject protections), and implementation and evaluation of Corrective and 
Preventative Action Plan (CAPA) procedures. 
10.1.9 
Data Handling and Record Keeping 
10.1.9.1 
Data Collection and Management Responsibilities 
Data collection is the responsibility of the study staff at the participating site under the 
supervision of the participating site PI. The participating site PI must maintain complete and 
accurate source documentation. 
Clinical research data from source documentation, including, but not limited to, AEs/SAEs, 
concomitant medications, medical history, physical assessments, and clinical laboratory data, 
will be entered by the participating site into eCRFs via a 21 CFR Part 11-compliant internet data 
entry system provided by the SDCC. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. AEs and concomitant medications will be coded according to the most 
current versions of MedDRA and WhoDrug, respectively. 
The SDCC for this study will be responsible for data management, quality review, analysis, and 
reporting of the study data. 

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The IND sponsor is responsible for review of data collection tools and processes, and review of 
data and reports. 
AEs will be coded according to the MedDRA dictionary version 23.0 or higher. 
A separate study specific Study Data Standardization Plan (SDSP) appendix will be developed 
which describes the technical recommendations for the submission of human study data and 
related information in a standardized electronic format throughout product development. 
At the end of the study, a copy of all datasets, including annotated CRFs and data dictionary, will 
be provided to DMID. 
10.1.9.2 
Study Record Retention 
Study-related records, including the regulatory file, study product accountability records, consent 
forms, subject source documents and electronic records, should be maintained for a period of 2 
years following the date a marketing application is approved for the investigational product for 
the indication for which it is being investigated; or, if no application is to be filed or if the 
application is not approved for such indication, until 2 years after the investigation is 
discontinued and FDA is notified. These documents should be retained for a longer period, 
however, if required by local policies or regulations. No records will be destroyed without the 
written consent of DMID. Consent forms with specimen retention linked to identifiable 
specimens will be maintained for as long as the specimens remain in identifiable format, and a 
minimum of three years after use of the identifiable specimens in nonexempt human subject 
research. 
10.1.9.3 
Source Records 
Source data are all information in original records (and certified copies of original records) of 
clinical findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data should be attributable, legible, 
contemporaneous, original, accurate, and complete. Each participating site will maintain 
appropriate medical and research records for this trial, in compliance with ICH GCP, regulatory, 
and institutional requirements. Data recorded in the eCRF derived from source documents should 
be consistent with the data recorded on the source documents. 
Interview of subjects is sufficient for obtaining medical history. Solicitation of medical records 
from the subject’s primary care provider is not required. 
10.1.10 
Protocol Deviations 
A protocol deviation is any non-compliance with the clinical trial protocol, any process that is 
noted in the protocol and refers to details in the protocol-specific MOP or GCP requirements, or 
any critical study procedures with specific instructions in ancillary documents referenced in the 
protocol such as a protocol-specific MOP. 
The non-compliance may be either on the part of the subject, the participating site PI or the study 
staff. Following a deviation(s), corrective actions should be developed by the participating site 
and implemented promptly. All individual protocol deviations will be addressed in subject study 
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It is the responsibility of the participating site PI and study staff to use continuous vigilance to 
identify and report deviations within five working days of identification of the protocol 
deviation, or within five working days of the scheduled protocol-required activity. All deviations 
must be promptly reported to DMID per the protocol deviation reporting procedures. Protocol 
deviations must be sent to the local IRB/IEC per their guidelines. The participating site PI and 
study staff are responsible for knowing and adhering to their IRB requirements. A completed 
copy of the DMID Protocol Deviation Form must be maintained in the Regulatory File, as well 
as in the subject’s chart if the deviation is subject specific. 
10.1.11 
Publication and Data Sharing Policy 
Analyses will be conducted as data become available while the study is ongoing at the discretion 
of the sponsor. Analyses of data will be available for publication to inform the scientific 
community. Data will be available immediately following publication, with no end date, with 
data sharing at the discretion of the PI. Publication of manuscripts may occur at the discretion of 
the sponsor in accordance with DMID’s Expanded Distribution of Clinical Research Endpoint 
Data Policy. 
10.1.12 
Human Data Sharing Plan 
This study will be conducted in accordance with the following publication and data sharing 
policies and regulations: 
• NIH Public Access Policy, which ensures that the public has access to the published 
results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon 
acceptance for publication. 
10.1.13 
Genomic Data Sharing (GDS) Plan 
This study will comply with the NIH GDS Policy, which applies to all NIH-funded research that 
generates large-scale human or non-human genomic data, as well as the use of these data for 
subsequent research. Large-scale data include genome-wide association studies (GWAS), SNP 
arrays, and genome sequence, transcriptomic, epigenomic, and gene expression data. 
10.1.14 
Publication 
At intervals throughout the study at the discretion of the sponsor and following completion of the 
study, the lead PI is expected to publish the results of this research in a scientific journal. This 
study will adhere to the following publication and data sharing policies and regulations: 
• NIH Public Access Policy, which ensures that the public has access to the published 
results of NIH funded research. As such, the final peer-reviewed journal manuscripts will 
be accessible to the public on PubMed Central no later than 12 months after publication. 
10.1.15 
Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 

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have such conflicts managed in a way that is appropriate to their participation in the design and 
conduct of this trial. DMID has established policies and procedures for all study team members 
to disclose all conflicts of interest and will establish a mechanism for the management of all 
reported dualities of interest. 
10.2 
Additional Considerations 
10.2.1 
Research Related Injuries 
For any potential research related injury, the participating site PI or designee will assess the 
subject. Study staff will try to reduce, control and treat any complications from this trial. 
Immediate medical treatment may be provided by the participating site, such as giving 
emergency medications to stop immediate allergic reactions to the vaccine. As needed, referrals 
to appropriate health care facilities will be provided to the subject. The participating site PI 
should then determine if an injury occurred as a direct result of the tests or treatments that are 
done for this trial. 
If it is determined by the participating site PI that an injury occurred to a subject as a direct result 
of the tests or treatments that are done for this trial, then referrals to appropriate health care 
facilities will be provided to the subject. Study staff will try to reduce, control and treat any 
complications from this trial. Immediate medical treatment may be provided by the participating 
site, such as giving emergency medications to stop immediate allergic reactions to the vaccine. 
No financial compensation will be provided to the subject by NIAID, NIH, the vaccine 
manufacturer, or the participating site for any injury suffered due to participation in this trial. 
For this protocol, the study vaccine, mRNA-1273, manufactured by ModernaTX, Inc. is covered 
under the PREP Act, as described in Section 2.1.1. 
10.3 
Abbreviations 
Table 10: Abbreviations 
2019-nCov 
2019-novel Coronavirus 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Transaminase 
AST 
Aspartate Transaminase 
BMI 
Body Mass Index 
BP 
Blood Pressure 
°C 
Degrees Celsius 
CAPA 
Corrective and Preventative Action Plan 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CICP 
Countermeasures Injury Compensation Program 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
CMS 
Clinical Material Services 
CMV 
Cytomegalovirus 

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COC 
Certificate of Confidentiality 
COPD 
Chronic Obstructive Pulmonary Disease 
CoV 
Coronavirus 
COVID-19 
Coronavirus Disease 2019 
Cr 
Creatinine 
CRF 
Case Report Form 
CROMS 
Clinical Research Operations and Management Support 
CSR 
Clinical Study Report 
CQMP 
Clinical Quality Management Plan 
DCF 
Data Collection Form 
DHHS 
Department of Health and Human Services 
DMID 
Division of Microbiology and Infectious Diseases 
DNA 
Deoxyribonucleic Acid 
DSPC 
1,2-distearoyl-sn-glycero-3-phosphocholine 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated Glomerular Filtration Rate 
ELISA 
Enzyme-Linked Immunosorbent Assay 
EUA 
Emergency Use Authorization 
°F 
Degrees Fahrenheit 
FDA 
Food and Drug Administration 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
GDS 
Genomic Data Sharing 
GLP 
Good Laboratory Practices 
GMFR 
Geometric Mean Fold Rise 
GMT 
Geometric Mean Titer 
GWAS 
Genome-Wide Association Studies 
hDPP4 
Dipeptidyl Peptidase 4 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
Hgb 
Hemoglobin 
HIV 
Human Immunodeficiency Virus 
HKU1 
Human Coronavirus HKU1 
HLA 
Human Leukocyte Antigen 
hMPV 
Human Metapneumovirus 
HR 
Heart Rate 
HRSA 
Health Resources and Services Administration 
IB 
Investigator’s Brochure 
ICD 
International Classification of Diseases 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IDCRC 
Infectious Disease Clinical Research Consortium 
IDE 
Investigational Device Exemption 
IEC 
Independent or Institutional Ethics Committee 

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IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IM 
Intramuscular 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
IV 
Intravenous 
kg 
Kilogram 
LNP 
Lipid Nanoparticle 
m 
Meter 
MAAE 
Medically-Attended Adverse Event 
mcg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities 
MERS 
Middle East Respiratory Syndrome 
mg 
Milligrams 
MI 
Myocardial Infarction 
min 
Minute 
mITT 
Modified Intent-To-Treat 
mL 
Milliliter 
mm Hg 
Millimeter of Mercury 
MOP 
Manual of Procedures 
mRNA 
Messenger Ribonucleic Acid 
N 
Number (typically refers to subjects) 
NaCl 
Sodium Chloride 
nCoV 
Novel Coronavirus 
NDA 
New Drug Application 
Neut 
Neutralizing 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NOAEL 
No-Observed-Adverse-Effect-Level 
NOCMC 
New-Onset Chronic Medical Condition 
OHRP 
Office for Human Research Protections 
PBMC 
Peripheral Blood Mononuclear Cell 
PEG 
Polyethylene Glycol 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PIV3 
Parainfluenza Virus Type 3 
PLT 
Platelet 
PP 
Per Protocol 
PREP Act 
Public Readiness and Emergency Preparedness Act 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
QA 
Quality Assurance 
QC 
Quality Control 

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RNA 
Ribonucleic Acid 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SARS 
Severe Acute Respiratory Syndrome 
SARS-CoV 
SARS Coronavirus 
SARS-CoV-2 
SARS Coronavirus 2 
SDCC 
Statistical and Data Coordinating Center 
SDSP 
Study Data Standardization Plan 
SMC 
Safety Monitoring Committee 
SNP 
Single Nucleotide Polymorphisms 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
T. Bili 
Total Bilirubin 
Th 
T helper 
UP 
Unanticipated Problem 
US 
United States 
USP 
United States Pharmacopeia 
VRC 
Vaccine Research Center 
WBC 
White Blood Cell 
WHO 
World Health Organization 
WIV1 
Chinese Horseshoe Bat Coronavirus WIV1 
 
10.4 
Protocol Amendment History 
Table 11: Protocol Amendment History 
Version, Date 
Section 
Description of Change  
Brief Rationale 
2.0,  
March 13, 
2020 
Throughout Administrative. 
Advanced version and date. 
Throughout Clarifications and modifications 
to resolve inconsistencies. 
To address Pre-IND, IND 
non-hold and PI comments. 
Sect. 1.1, 
Page 7 
Updated COVID-19 case 
counts. 
 
Sect. 2.1, 
Page 14 
Updated COVID-19 status. 
 
Sect. 4.1, 
Page 22 
Enrollment will occur at up to 
three one domestic clinical 
research sites. 
Revised language to add 
clinical research sites. 
Sect. 1.2, 
Table 4 and 
Sect. 8.2, 
Table 9 
Adjusted visit windows. 
 

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Version, Date 
Section 
Description of Change  
Brief Rationale 
Sect. 5.1, 
Page 26 
Added Inclusion Criterion #16: 
The subject must agree to 
refrain from donating blood or 
plasma during the study 
(outside of this study). 
Moved from Exclusion 
Criterion #22. 
Sect. 5.2, 
Page 28 
Revised Exclusion Criterion 
#21: 
Close contact of anyone known 
to have SARS-CoV-2 infection 
within 30 days prior to vaccine 
administration. 
Increased duration from 2 
weeks to 30 days from 
known contact. 
Sect. 5.2, 
Page 28 
Deleted Exclusion Criterion 
#22: 
Has traveled to 
countries/regions with known 
widespread community 
transmission of SARS-CoV-2 
(e.g., China, regions in Italy, 
South Korea, Iran, or other 
countries based on the most 
updated epidemiology at the 
time of study enrollment) 
within 30 days before the first 
vaccination. 
Addressed in revision to 
Exclusion Criterion #21. 
Sect. 5.4, 
Page 29 
Revised lifestyle considerations.  
Sect. 6.1.2, 
Page 31 
Revised dosing and 
administration instructions. 
 
Sect. 6.2.1, 
Page 33 
Revised product destruction and 
storage instructions. 
 
Sect. 7.1, 
Page 36 
Revised halting and sentinel 
halting criteria. 
Halting Criterion #5 revised: 
Three (3) or more subjects 
experience a Grade 3 AE 
(unsolicited systemic and/or 
clinical laboratory abnormality), 
in the same Preferred Terms 
based on the Medical 
Dictionary for Regulatory 
Activities (MedDRA) coding, 
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Version, Date 
Section 
Description of Change  
Brief Rationale 
administration of the vaccine 
and is considered related to the 
vaccine. 
Sect. 7.1.3, 
Page 37 
Revised dosing and redosing 
criteria 
 
Sect. 8.1.2, 
Page 42 
Added research laboratory 
location and contact 
information 
 
Sect. 8.2, 
Table 9 
Adjusted blood volumes. 
 
Sect. 8.3.9 
Clarified AESIs reporting. 
 
Sect. 2.1.1 
Added PREP Act. 
 
3.0,  
March 30, 
2020 
Throughout Administrative. 
Advanced version and date. 
Sect. 2.1.1 
Revised PREP Act language. 
To address Office of General 
Counsel comments. 
Sect. 5.1 
and 5.2 
Refined eligibility criteria. 
To address PI comments. 
Sect. 8.1.3 
Removed previous Table 8: 
Testing Laboratories. 
Details moved to protocol-
specific MOP. 
Throughout Included cohorts >55 years of 
age. 
To rapidly assess clinical 
safety of novel vaccines in 
this vulnerable population as 
early as possible, based on 
currently available 
information and clinical 
experience suggesting that 
older adults may be at higher 
risk for severe illness from 
COVID-19. 
Throughout Included leukapheresis for a 
subset of subjects. 
To support development of 
diagnostics, therapeutics and 
vaccines. 
4.0,  
May 20, 2020 
Throughout Administrative. 
Advanced version and date. 
Sect. 2.1 
Updated SARS-CoV-2 case 
counts, deaths and status. 
To be current as of May 14, 
2020. 
Sect. 2.1 
Updated animal data. 
To include additional 
immune response data in 
mice. 
Sect. 2.2.1, 
Risks of 
mRNA-
1273 
Included animal data. 
To add non-GLP toxicity 
data in rats. 

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Version, Date 
Section 
Description of Change  
Brief Rationale 
Sect. 2.2.1, 
Risks of 
mRNA-
1273 
Included preliminary safety data 
from this ongoing phase I 
clinical trial. 
To advise study design 
changes. 
Sect. 2.2.1, 
Risks of 
mRNA-
1273 
Updated non SARS-CoV-2 
clinical studies. 
To be consistent with 
updated IB v2.0, 18 May 
2020. 
Sect. 2.2.1, 
Risks of 
mRNA-
1273 
Deleted duplicate paragraph on 
risks. 
Same text already included 
in this section. 
Sect. 2.2.1, 
Risks of 
mRNA-
1273 
Updated enhanced 
immunopathology data in 
animals. 
To include immune response 
data in mice. 
Throughout 
and Sect. 
4.1. 
Included 10 and 50 mcg dosage 
cohorts and updated the number 
of cohorts and subjects. 
To further explore dose-
ranging. 
Throughout 
and Sect. 
4.1 
Revised timing and added 
conditions for enrollment of 
cohorts 6 and 9. 
Based on preliminary safety 
data from this ongoing phase 
I clinical trial. 
Throughout 
and Sect. 
4.1 
Included timing and added 
conditions for enrollment of 
cohorts 10-13. 
To be consistent with study 
design changes. 
Throughout 
and Sect. 
4.1 
Updated/included timing of 
early and Day 57 data reviews 
for cohorts, 6 and 9-13.  
To be consistent with study 
design changes. 
Throughout 
and Sect. 
4.1 
Revised cohorts eligible for 
leukapheresis. 
To be consistent with study 
design changes. 
Sect. 5 
Updated estimated time from 
initiation of enrollment to 
complete enrollment in this 
clinical trial from 
approximately 12 to 16 weeks. 
To compensate for the 
inclusion of additional 
cohorts. 
Sect. 5.1 
Updated Inclusion Criteria for 
BMI and Systolic BP. 
Per Letter of Amendment 
dated April 10, 2020. 
Sect. 5.1.1 
Updated Leukapheresis 
Inclusion Criteria for cohorts 
eligible for leukapheresis. 
To be consistent with study 
design changes. 
Sect. 5.2 
Updated Exclusion Criteria for 
chronic kidney disease eGFR 
value, as well as for subjects 
≥56 years of age - history of 
Per Letter of Amendment 
dated April 10, 2020. 

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Version, Date 
Section 
Description of Change  
Brief Rationale 
chronic smoking, current 
smoking or vaping and 
individuals currently working 
with high risk of exposure to 
SARS-CoV-2. 
Throughout 
and Sect. 
6.1.2, 
Table 7 
Updated dosing and 
administration to include 10 and 
50 mcg dosage cohorts. 
To further explore dose-
ranging and be consistent 
with study design changes. 
Sect. 6.1.2 
Added/updated the expiration 
time of the dosing syringe 
containing the prepared mRNA-
1273 solution to 4 hours at 
room temperature for the 10 
mcg dosage after the solution is 
drawn into the dosing syringe 
and 8 hours at room 
temperature for the 25, 50, 100, 
and 250 mcg dosages after the 
solution is drawn into the 
dosing syringe. 
To be consistent with 
updated pharmacy manual. 
Sect. 6.2.1 
Updated study product 
accountability and destruction 
instructions for used and unused 
mRNA-1273 vials, used mixing 
vials and mRNA-1273 cartons. 
To allow for study product 
accountability and 
destruction in accordance 
with site-specific SOPs and 
with second verification as 
well as documentation to 
include a certificate of 
destruction or document of 
destruction. 
Sect. 6.2.3 
Added stability of prepared 10 
mcg doses – up to 4 hours at 
room temperature.  
To be consistent with 
updated pharmacy manual. 
Sect. 6.3.1 
Updated/added Treatment 
Assignment Procedures for 
cohorts 6 and 9-13. 
To be consistent with study 
design changes. 
Throughout Changed participant(s) to 
subject(s). 
To be consistent. 
Sect. 9.2 
Updated Sample Size 
Determination. 
To be consistent with study 
design changes. 
Sect. 9.4.6 
Added “other participating 
laboratories” to the list of those 
involved in jointly developing 
ad-hoc analyses. 
To be consistent with current 
practice. 

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Version, Date 
Section 
Description of Change  
Brief Rationale 
Sect. 
9.4.6.1 and 
10.1.6.2. 
Updated Interim Safety 
Analyses to clarify: 
“Cumulative AE data will also 
be provided to the SMC after all 
subjects in all cohorts have 
completed Day 36.”  
To be consistent with study 
design changes and current 
practice. 
Sect. 
9.4.6.3 
Updated Interim 
Immunogenicity and Safety 
Review for additional separate 
interim analyses through Day 
57 to be conducted as needed. 
To be consistent with study 
design changes and current 
practice. 
Sect.10.1.1
4 
Updated Publication with: “At 
intervals throughout the study at 
the discretion of the sponsor 
and…” 
To allow for additional 
publications of results in 
scientific journals before the 
completion of the study. 
Throughout 
and Sect. 
10.3, 
Table 10 
Updated abbreviations. 
 
Sect. 11 
Updated references. 
 
Protocol 
Summary 
Updated anticipated duration of 
entire study from 18 to 20 
months (from start of screening 
to last subject last visit). 
To compensate for the 
inclusion of additional 
cohorts. 
5.0,  
December 4, 
2020 
Throughout Administrative. 
Advanced version and date. 
Protocol 
Summary 
50 mcg dosage added. 
Inadvertently not included in 
previous amendment. 
Protocol 
Summary 
and Sect. 3 
“3” dosages changed to “5”. 
Inadvertently not included in 
previous amendment. 
Protocol 
Summary, 
Sect. 3, 4.1, 
8.1.3, 
8.1.4.1, and 
9.4.9 
Exploratory objective, 
endpoints and supportive text 
for B cell analyses removed. 
To be considered for 
secondary research instead of 
primary research. 
Sect. 6.4 
Changed “entered into the 
electronic case report form 
eCRF)” to “recorded on the 
appropriate DCF.” 
Administrative. 
Sect. 9.4, 
9.4.6.2 and 
9.4.6.3 
Interim Immunogenicity and 
Safety Review revised. 
To align with what was or 
will be done in the study. 

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Version, Date 
Section 
Description of Change  
Brief Rationale 
Sect. 9.4 
Summary of Statistical 
Analyses (interim and final 
analyses as well as final data 
lock timing) and CSR plans 
revised. 
To align with what was or 
will be done in the study. 
Sect. 
9.4.6.1 and 
10.1.6.2 
SMC meeting plan for Interim 
Safety Analyses revised. 
To align with what was done 
in the study. 
Sect. 
10.1.1. and 
10.1.1.2 
Consenting specifically to 
genetic testing, including DMD 
sequencing removed from 
primary research and added to 
secondary research. 
Genetic testing will not be 
included as primary research. 
No change to ICF needed, 
because genetic testing is 
already included as 
secondary research and not 
included as primary research 
in the ICF. 
Sect. 
10.1.6.2 
Number of SMC members 
changed from “3” to “2-3”. 
To align with what was done 
in the study. 
Sect. 
10.1.6.2 
Clarified that SMC materials 
will be provided electronically. 
To align with what was done 
in the study. 
Sect. 
10.1.6.2 
Removed “The SMC will 
review blinded aggregate data 
in the open session of the SMC 
meetings.” 
To align with what was done 
in this open-label study. 
Sect. 10.1.7 Abbreviation for electronic case 
reports forms added. 
Administrative. 
6.0,  
January 28, 
2021 
Throughout Administrative. 
Advanced version and date. 
Throughout *Cohorts 6, 9 and 13 were not 
enrolled. 
Updates to the study. 
Throughout OneUp to one 
Administrative. 
Throughout lastsecond 
Administrative. 
Throughout Based on interim 
immunogenicity and 
reactogenicity data, Cohorts 6, 
9 and 13 were not enrolled. 
Updates to the study. 
Throughout main study 
Administrative. 
Protocol 
Summary, 
Study 
Design 
Added text. 
Updates to the study, 
including added the Optional 
Third mRNA-1273 
Vaccination SubStudy. 

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Section 
Description of Change  
Brief Rationale 
Protocol 
Summary, 
Study 
Duration 
The duration of the optional 
third mRNA-1273 vaccination 
substudy is anticipated to be 12 
months from the last subject 
vaccinated with the third 
mRNA-1273 vaccination. 
Added the Optional Third 
mRNA-1273 Vaccination 
SubStudy. 
Protocol 
Summary, 
Subject 
Duration 
The duration for each individual 
subject in the optional third 
mRNA-1273 vaccination 
substudy is approximately 26 
months (from first contact to 
last visit). 
Added the Optional Third 
mRNA-1273 Vaccination 
SubStudy. 
Protocol 
Summary, 
Safety 
See Section 12, Appendix A for 
halting rules for the optional 
third mRNA-1273 vaccination 
substudy. 
Added the Optional Third 
mRNA-1273 Vaccination 
SubStudy. 
Protocol 
Summary, 
Safety 
The SMC does not need to meet 
for dose escalation or for 
initiation of the optional third 
mRNA-1273 vaccination 
substudy. 
Added the Optional Third 
mRNA-1273 Vaccination 
SubStudy. 
Sect. 1.2, 
Table 4 
g) Subjects who participate in 
the optional third mRNA-1273 
vaccination substudy will exit 
the Schedule of Activities for 
the main study between Visit 13 
and the close of the window for 
Visit 14 and will not have Visit 
14, instead will have Visit 14A 
and subsequent substudy visits. 
See Section 12, Appendix A for 
the Schedule of Activities for 
the optional third mRNA-1273 
vaccination substudy. 
Added the Optional Third 
mRNA-1273 Vaccination 
SubStudy. 
Sect. 2.2.1, 
Risks of 
mRNA-
1273 
Added and deleted text. 
Updates to the study and 
added new information. 
Sect. 2.2.2 
As outlined in Section 12.2, 
data from the Phase 3 placebo-
controlled clinical trial of 
mRNA-1273 (COVE) suggests 
94.1% efficacy of the vaccine 
when administered at 100 mcg 
Updates to the study and 
added new information. 

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versus placebo against SARS-
CoV-2 infection when assessed 
on November 25, 2020 (Baden 
LR et al, 2020). The efficacy of 
other doses of mRNA-1273 
(e.g., 25, 50, or 250 mcg) is not 
known. Although declines in 
binding and neutralizing 
antibodies are observed over 
time, 100 mcg of mRNA-1273 
has the potential to provide 
durable humoral immunity 
(Widge AT et al, 2020). 
Sect. 4.4 
Added new section. 
Optional Third mRNA-1273 
Vaccination SubStudy. 
Sect. 8.2, 
Table 8 
5 Subjects who participate in the 
optional third mRNA-1273 
vaccination substudy will exit 
the Schedule of Activities for 
the main study between Visit 13 
and the close of the window for 
Visit 14 and will not have Visit 
14, instead will have Visit 14A 
and subsequent substudy visits. 
See Section 12, Appendix A for 
the Schedule of Activities for 
the optional third mRNA-1273 
vaccination substudy. 
Added the Optional Third 
mRNA-1273 Vaccination 
SubStudy. 
Sect. 9.3 
The Safety Analysis population 
for the main study includes all 
subjects who received one dose 
of vaccine. Analyses for the 
primary safety population will 
include safety reported through 
the end of the main study. A 
modified primary safety 
population analysis will also be 
performed that excludes safety 
data collected after subjects 
receive either the third mRNA-
1273 vaccination in the optional 
substudy or non-study EUA 
vaccine, if applicable. 
Updated for main study and 
substudy. 

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Sect. 
10.1.6.2 
The SMC does not need to meet 
for dose escalation to 250 mcg 
(cohorts 3, 6 and 9) or for 
initiation of the optional third 
mRNA-1273 vaccination 
substudy. 
The SMC will meet when trial 
or optional third mRNA-1273 
vaccination substudy halting 
criteria are met, or as requested 
by the sponsor or PI. 
Ad hoc reviews will occur when 
trial halting criteria are met, or 
as requested by the sponsor or 
PI. 
The SMC will have a final 
review meeting at the end of the 
studytrial, defined as the end of 
the optional third mRNA-1273 
vaccination substudy. 
Added the Optional Third 
mRNA-1273 Vaccination 
SubStudy. 
Sect. 10.3, 
Table 10 
Abbreviations for emergency 
use authorization (EUA) and 
polyethylene glycol (PEG) 
added. 
Administrative. 
Sect. 11 
Added references. 
Updates to the study. 
Sect. 12, 
Appendix 
A 
Added new section. 
Optional Third mRNA-1273 
Vaccination SubStudy. 
7.0,  
July 30, 2021 
Throughout Administrative. 
Advanced version and date. 
Throughout Added protocol specified 
adverse events of special 
interest (AESIs). 
Myocarditis and pericarditis 
classified as protocol 
specified AESIs to address 
Manufacturer surveillance 
request.. 
Protocol 
Summary, 
Safety 
Deleted: See Section 12, 
Appendix A for halting rules for 
the optional third mRNA-1273 
vaccination substudy. 
No special halting rules for 
the Optional Third mRNA-
1273 Vaccination Substudy. 
Sect. 2.2.1 
Myocarditis and pericarditis 
added to the risks of mRNA-
1273. 
Per updated Moderna 
COVID-19 EUA Vaccine 
Fact Sheet. 
 

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11. 
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'Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen', 
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21. Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., 
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Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, 
Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, 
Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized 
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26. Widge, A. T., Rouphael, N. G., Jackson, L. A., Anderson, E. J., Roberts, P. C., Makhene, M., 
Chappell, J. D., Denison, M. R., Stevens, L. J., Pruijssers, A. J., McDermott, A. B., Flach, B., 
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antibodies targeting different domains and functions of the MERS-coronavirus spike 
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Scientific Reports, 5: 13133. 
 
 
 

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12. 
APPENDIX A: OPTIONAL THIRD MRNA-1273 
VACCINATION SUBSTUDY 
All aspects of the main study apply to this substudy unless otherwise specified in Section 12, 
Appendix A. 
12.1 
Overview 
All subjects in this clinical trial were scheduled to receive two mRNA-1273 vaccinations, 28 
days apart, at dosages of 25, 50, 100, or 250 mcg (see Table 1), with the last scheduled follow-up 
visit occurring at 365 days after the second vaccination (see Table 4). During the course of the 
main study, interim efficacy data from a Phase 3 placebo-controlled clinical trial of mRNA-1273 
(COVE), administered as 2 doses of 100 mcg given 28 days apart, demonstrated vaccine efficacy 
of 94.1% (95% CI: 89.3%, 96.8%) for the prevention of symptomatic, confirmed COVID-19 
(Baden, LR, et al. 2020). After review of the interim safety and efficacy data from that clinical 
trial, the FDA granted on December 18, 2020 an Emergency Use Authorization (EUA) for the 
mRNA-1273 vaccine in adults 18 years of age and older. 
To potentially enhance and extend the duration of protection provided by the 2-dose vaccination 
schedule of mRNA-1273 administered in the main study, and to gain an understanding of the 
immune responses to a third dose of mRNA-1273, subjects in the main study may participate in 
an optional third mRNA-1273 vaccination substudy, detailed in Section 12, Appendix A. 
Substudy subjects will receive a third mRNA-1273 vaccination, administered via an IM injection 
at a dosage of 100 mcg/0.5 mL, given six to twelve months after receipt of their second 
vaccination in the main study. Substudy subjects will be followed for safety, reactogenicity, and 
immunogenicity endpoints through 12 months post third vaccination (Substudy Day 366). 
To be eligible to participate in the substudy, subjects must have received both the first and 
second mRNA-1273 vaccinations in the main study. Other eligibility criteria are specified in 
Appendix A. Subjects who received only one mRNA-1273 vaccination in the main study will be 
advised to receive an FDA authorized or approved COVID-19 vaccine, according to the 
recommended schedule, when available to them outside of this trial, unless they have a 
contraindication to COVID-19 vaccines that are available. 
Subjects who elect not to participate in the optional third mRNA-1273 vaccination substudy or 
are not eligible for the substudy will continue to be followed according to the Schedule of 
Activities for the main study (see Table 4) with the Final Study Visit 14 occurring at Day 394 
(±14 days). 
Dosing for the optional third mRNA-1273 vaccination substudy is found in Table 13. 
Schedule of assessments for the optional third mRNA-1273 vaccination substudy is found in 
Table 14. 
Statistical Considerations for the optional third mRNA-1273 vaccination substudy are found in 
Section 12.11. 
12.2 
Background and Scientific Rationale 
See Section 2.1 for additional background information. 

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In December 2019 the Wuhan Municipal Health Committee identified an outbreak of viral 
pneumonia that was ultimately identified as a novel pathogen named SARS-CoV-2. The disease 
caused by SARS-CoV-2 is called Coronavirus disease 2019 (COVID-19). On January 30, 2020, 
the International Health Regulations Emergency Committee of the World Health Organization 
(WHO) declared the COVID-19 outbreak a Public Health Emergency of International Concern. 
On January 31, 2020, the US Department of Health and Human Services declared a public health 
emergency in the United States. On March 11, 2020 the WHO declared COVID-19 a pandemic. 
As of January 10, 2021, the Center for Systems Science and Engineering (CSSE) at Johns 
Hopkins University (systems.jhu.edu) reports a global tally of 89,960,893 cases and 1,931,083 
deaths and a total of 22,227,722 cases and 373,331 deaths in the United States. Morbidity and 
mortality have disproportionately affected older adults, and racial and ethnic minority 
populations (Garg S et al, 2020). 
Despite success in developing a novel antiviral – remdesivir (Beigel JH et al, 2020), use of 
steroids and other novel immunomodulators (Kalil AC et al, 2020; Recovery Collaborative 
Group et al, 2020), and use of monoclonal antibodies (Chen P et al, 2020) for prevention and 
treatment of SARS-CoV-2 infection and COVID-19 disease, mortality remains substantial. 
Therefore, there is an urgent public health need for vaccines against SARS-CoV-2. Currently, 
there are over 170 vaccines in preclinical development and 60 vaccines that have entered into 
clinical trials (https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-
vaccines). In the US, 2 mRNA vaccines [Moderna (mRNA-1273), Pfizer-BioNTech 
(BNT162b2)] received FDA EUA in December 2020. 
Studies of mRNA-1273 have been conducted in both mice and nonhuman primates (rhesus 
macaques) (Corbett KS et al, N Engl J Med 2020). A single dose of mRNA-1273 in mice elicited 
robust S protein binding antibody titers, but with no virus neutralization activity observed 
(Corbett KS et al, Nature 2020). Mice from this study were challenged with mouse-adapted 
SARS-CoV-2 virus, and preliminary results indicate that mRNA-1273-induced immunity is 
protective after challenge. Similarly, rhesus macaques also had a dose-dependent response to 
vaccination (Corbett KS et al, N Engl J Med 2020). The mRNA-1273 vaccine candidate induced 
antibody levels exceeding those in human convalescent-phase serum. Vaccination induced type 1 
helper T cell (Th1)–biased CD4 T cell responses and low or undetectable Th2 or CD8 T cell 
responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of 
eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of 
the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or 
detectable viral genome or antigen was noted in lungs of animals in either vaccine group. 
This phase I clinical trial is evaluating safety and immunogenicity of variable doses of 
Moderna’s mRNA-1273 in healthy adults across the age spectrum (≥18 years of age). Cohorts 
now include subjects who received two doses of 25, 50, and 100 mcg in all 3 age ranges, and 250 
mcg in those 18-55 years of age. A total of 120 subjects have been enrolled to assess the safety, 
reactogenicity, and immunogenicity of the mRNA-1273. To date, no serious adverse events have 
occurred, and no safety concerns have been identified (Jackson LA et al, 2020; Anderson EJ et 
al, 2020; Widge AT et al, 2020). Dose-dependent reactogenicity has occurred, with 
reactogenicity generally being greater with the second dose. This was typically mild-moderate in 
severity, and usually resolved within a few days. The second 250 mcg dose had increased 
reactogenicity in the 18-55 year old cohort and given high binding and neutralizing antibodies 
with lower doses, a dose of 50 or 100 mcg was chosen for the Phase 2 placebo-controlled, dose-

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confirmation clinical trial of mRNA-1273 (Jackson LA et al, 2020). Binding and neutralizing 
antibodies, and T cell responses were dose-dependent (Jackson LA et al, 2020; Anderson EJ et 
al, 2020). Responses at 1 month after the second dose were generally greater than those observed 
in sera of patients convalescing from COVID-19. A CD4 cytokine response occurred particularly 
among type 1 helper T cells. 
Although declines in binding and neutralizing antibodies are observed by 3 months after the 
boost dose, recipients that had received 100 mcg of mRNA-1273 still had binding and 
neutralizing antibody titers that were similar to or exceeded that of convalescent sera (Jackson 
LA et al, 2020; Anderson EJ et al, 2020; Widge AT et al, 2020). Data through 6 months after the 
boost dose are pending. 
A Phase 2 placebo-controlled, dose-confirmation clinical trial of mRNA-1273 (NCT04405076) 
is being conducted in adults using a prime-boost regimen of 50 mcg, 100 mcg, or placebo in 18-
<55 year old and ≥55 year old subjects. This trial is ongoing, but publicly available data are 
limited. 
A Phase 3 placebo-controlled clinical trial of mRNA-1273 (NCT04470427, the COVE study) 
was initiated at almost 100 sites in the United States that enrolled 30,420 adults and administered 
two doses of either 100 mcg of mRNA-1273 or placebo (saline) (Baden LR et al, 2020). Risks to 
subjects receiving mRNA-1273 were primarily mild to moderate injection site reactions, 
particularly pain. Delayed injection-site reactions (those with onset on or after day 8) were noted 
in 244 subjects (0.8%) after the first dose and in 68 subjects (0.2%) after the second dose. 
Systemic reactions were transient and included fever, fatigue, chills, headache, myalgias, and 
arthralgias. Solicited systemic adverse events occurred more often in the mRNA-1273 group 
than in the placebo group after both the first dose (54.9%, vs. 42.2%) and the second dose 
(79.4%, vs. 36.5%). The severity of the solicited systemic events increased after the second dose 
in the mRNA-1273 group, with an increase in proportions of grade 2 events (from 16.5% after 
the first dose to 38.1% after the second dose) and grade 3 events (from 2.9% to 15.8%). Solicited 
systemic adverse events in the mRNA-1273 group lasted a mean of 2.6 days and 3.1 days after 
the first and second doses, respectively. Both solicited injection-site and systemic adverse events 
were more common among younger subjects (18 to <65 years of age) than among older subjects 
(≥65 years of age). Serious adverse events were rare, and the incidence was similar in the two 
groups. The frequency of grade 3 adverse events in the placebo group (1.3%) was similar to that 
in the vaccine group (1.5%), as were the frequencies of medically attended adverse events (9.7% 
vs. 9.0%) and serious adverse events (0.6% in both groups). Hypersensitivity reactions were 
reported in 1.5% and 1.1% of subjects in the vaccine and placebo groups, respectively. 
In the primary efficacy analysis of the Phase 3 placebo-controlled clinical trial of mRNA-1273 
(COVE), 196 cases of COVID-19 were diagnosed: 11 cases in the vaccine group (3.3 per 1000 
person-years; 95% CI, 1.7 to 6.0) and 185 cases in the placebo group (56.5 per 1000 person-
years; 95% CI, 48.7 to 65.3), indicating 94.1% efficacy of the mRNA-1273 vaccine (95% CI, 
89.3 to 96.8%; P<0.001) for the prevention of symptomatic SARS-CoV-2 infection as compared 
with placebo. Findings were similar across key secondary analyses, including assessment starting 
14 days after dose 1. Thirty subjects in the trial had severe COVID-19; all 30 were in the placebo 
group (indicating vaccine efficacy against severe COVID-19 of 100% [95% CI, could not be 
estimated to 1.0]), and one death among these subjects was attributed to COVID-19. The vaccine 

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efficacy to prevent COVID-19 was consistent across subgroups stratified by demographic and 
baseline characteristics. 
It has been observed that antibodies may decline in patients previously infected with mild SARS-
CoV-2 and that reinfection can occur (although perhaps infrequently symptomatic) (Ibarrondo FJ 
et al, 2020; Lumley SF et al, 2020). T cells and memory B cells are established after initial 
infection and remain present through 6 months after initial infection (Hartley GE et al, 2020). 
Additionally, the correlate or correlates of protection against COVID-19-related disease are not 
known, although active investigations are underway. Samples obtained from the Phase 3 clinical 
trials may provide insight into the correlate or correlates of protection. 
The durability of the immune response to mRNA-1273 remains uncertain beyond 3 months after 
the second vaccination (Widge AT et al, 2020). Immune responses after vaccination in general 
are known to wane, sometimes to the point where wild-type disease can occur. Since immunity 
after natural SARS-CoV-2 infection is not lifelong and no correlate of protection has been 
identified yet, a study to assess the safety, reactogenicity, and immunogenicity of a third dose of 
mRNA-1273 is warranted. Additionally, some subjects in this trial have received less (25 and 50 
mcg) than the 100 mcg dosage utilized in the Phase 3 placebo-controlled clinical trial of mRNA-
1273 (COVE) that resulted in the EUA for mRNA-1273. These subjects could directly benefit 
from an additional vaccination that might boost their serological and cellular responses. Since T 
cells and memory B cells are established after initial infection through at least 6 months, it is 
likely that SARS-CoV-2 revaccination will result in robust serological responses, even among 
those that received less than the authorized dose (e.g., 25 mcg, 50 mcg) of mRNA-1273. 
12.2.1 
Justification for Dose 
It is not known whether a third mRNA-1273 vaccination will elicit immune responses or enhance 
immunity elicited by the 2-dose vaccination schedule of mRNA-1273 administered in the main 
study. If such responses can be induced, the optimal number of doses and interval between 
vaccinations is also not known. The EUA was granted for the 2-dose 100 mcg regimen evaluated 
in the Phase 3 placebo-controlled clinical trial of mRNA-1273 (NCT04470427, the COVE 
study), and 100 mcg is the dosage likely to be used in the future if additional mRNA-1273 
vaccinations are recommended. Therefore, the 100 mcg dosage was selected for evaluation in 
this substudy. 
12.3 
Risk/Benefit Assessment 
12.3.1 
Known Potential Risks 
The potential risks of participating in this substudy are those associated with having blood 
drawn, IM injection, possible reactions to mRNA-1273, and breach of confidentiality. These and 
additional risks are described in Section 2.2.1. 
A third vaccination of mRNA-1273 has not been evaluated in humans. The risks are expected to 
be similar to the risks associated with the first and second mRNA-1273 vaccinations in the main 
study but it is possible that there may be unanticipated risks with the third mRNA-1273 
vaccination. 

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In a prior Phase 1 dose-ranging study of CMV vaccines (mRNA-1647 and mRNA-1443) with 
doses administered at 0, 1, and 6 months (NCT03382405), no safety issues were identified after 
the late third dose of mRNA vaccine (at 6 months after initial dose). 
12.3.2 
Known Potential Benefits 
As outlined in Section 12.2, data from the Phase 3 placebo-controlled clinical trial of mRNA-
1273 (COVE) suggests 94.1% efficacy of the vaccine when administered at 100 mcg versus 
placebo against SARS-CoV-2 infection when assessed on November 25, 2020 (Baden LR et al, 
2020). The efficacy of other doses of mRNA-1273 (e.g., 25, 50, or 250 mcg) is not known. 
Although declines in binding and neutralizing antibodies are observed over time, 100 mcg of 
mRNA-1273 has the potential to provide durable humoral immunity (Widge AT et al, 2020). 
Administration of a third dose of 100 mcg of mRNA-1273 vaccine might boost cellular 
responses and binding and neutralizing antibody titers in prior mRNA-1273 recipients. This 
could provide a boost in immune responses in subjects that received a lower vaccine dose (i.e., 
25 mcg, 50 mcg) than that used in the Phase 3 placebo-controlled clinical trial of mRNA-1273 
(COVE). Additionally, this third mRNA-1273 vaccination of prior 100 mcg or 250 mcg 2-dose 
recipients could boost the immune responses directed against the Spike protein of SARS-CoV-2. 
It is unknown as to whether a third mRNA-1273 vaccination will provide additional protection 
against SARS-CoV-2 infection. 
There is potential benefit to society as a result of information gained from participation in this 
optional third mRNA-1273 vaccination substudy. Data on the safety and immunogenicity of a 
third mRNA-1273 vaccination of mRNA-1273 could provide key insights to inform the response 
to the ongoing threat imposed by the SARS-CoV-2 pandemic. 
12.4 
Objectives and Endpoints 
Table 12: Objectives and Endpoints (Outcome Measures) 
OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
Primary 
 
• 
To evaluate the safety and reactogenicity 
of a third mRNA-1273 vaccination, at a 
dosage of 100 mcg. 
• 
Frequency and grade of each solicited 
local and systemic reactogenicity AE 
during a 7-day follow-up period post third 
mRNA-1273 vaccination. 
• 
Frequency and grade of any unsolicited 
AEs during the 28-day follow-up period 
post third mRNA-1273 vaccination. 
• 
Frequency of any SAEs, Protocol 
Specified AESIs, NOCMCs, and MAAEs 
from Substudy Day 1 to Substudy Day 
366. 
Secondary 
 

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OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
• 
To evaluate the immunogenicity as 
measured by IgG ELISA to the SARS-
CoV-2 S (spike) protein following a third 
mRNA-1273 vaccination, at a dosage of 
100 mcg, at all timepoints after the third 
mRNA-1273 vaccination. 
• 
GMT of antibody at each timepoint after 
the third mRNA-1273 vaccination. 
• 
Percentage of subjects who seroconverted, 
defined as a 4-fold change in antibody 
titer from the pre-third mRNA-1273 dose 
baseline (Substudy Day 1) at each post-
vaccination timepoint and pre-first 
mRNA-1273  dose baseline (Main Study 
Day 1). 
• 
The GMFR in IgG titer from the pre-third 
mRNA-1273 dose baseline (Substudy Day 
1) at each post-vaccination timepoint and 
pre-first mRNA-1273 dose baseline (Main 
Study Day 1). 
Exploratory 
 
• To evaluate the immunogenicity as 
measured by pseudovirus neutralization 
and other viral neutralization assays 
following a third mRNA-1273 
vaccination, at a dosage of 100 mcg. 
• 
GMT of Neut antibody at each timepoint 
after the third mRNA-1273 vaccination. 
• 
Percentage of subjects who seroconverted, 
defined as a 4-fold change in Neut 
antibody titer from the pre-third mRNA-
1273 dose baseline (Substudy Day 1) at 
each post-vaccination timepoint and pre-
first mRNA-1273 dose baseline (Main 
Study Day 1). 
• 
The GMFR Neut antibody titer from the 
pre-third mRNA-1273 dose baseline 
(Substudy Day 1) at each post-vaccination 
timepoint and pre-first mRNA-1273 dose 
baseline (Main Study Day 1). 

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OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
• 
To evaluate the immunogenicity as 
measured by live SARS-CoV-2 
neutralization following a third mRNA-
1273 vaccination, at a dosage of 100 mcg. 
• 
GMT of Neut antibody at each timepoint 
after third mRNA-1273 vaccination. 
• 
Percentage of subjects who seroconverted, 
defined as a 4-fold change in Neut 
antibody titer from the pre-third mRNA-
1273 dose baseline (Substudy Day 1) at 
each post-vaccination timepoint and pre-
first mRNA-1273 dose baseline (Main 
Study Day 1). 
• 
The GMFR in Neut antibody titer from 
the pre-third mRNA-1273 dose baseline 
(Substudy Day 1) at each post-vaccination 
timepoint and pre-first mRNA-1273 dose 
baseline (Main Study Day 1). 
• 
To assess, in at least a subset of samples, 
the SARS-CoV-2 S protein-specific T cell 
responses. 
• 
Magnitude, phenotype, and percentage of 
cytokine producing S protein-specific T 
cells, as measured by flow cytometry at 
timepoints pre- and post-third mRNA-
1273 vaccination. 
• 
To evaluate using a multiplex assay IgG 
ELISA to SARS-CoV-2 S protein and 
SARS-CoV-2 N protein. 
For each antigen, 
• 
GMT of antibody at each timepoint after 
the third mRNA-1273 vaccination. 
• 
Percentage of subjects who seroconverted, 
defined as a 4-fold change in antibody 
titer from the pre-third mRNA-1273 dose 
baseline (Substudy Day 1) at each post-
vaccination timepoint and pre-first 
mRNA-1273 dose baseline (Main Study 
Day 1). 
• 
The GMFR in IgG titer from the pre-third 
mRNA-1273 dose baseline (Substudy Day 
1) at each post-vaccination timepoint and 
pre-first mRNA-1273 dose baseline (Main 
Study Day 1). 
12.5 
Study Design 

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This is a substudy to a phase I, open-label, dose-ranging clinical trial to assess a third mRNA-
1273 vaccination, administered via an IM injection at a dosage of 100 mcg/0.5 mL, in subjects, 
18 years of age and older, who received both the first and second mRNA-1273 vaccinations in 
the main study (see Table 13) and meet all other substudy eligibility criteria. This optional third 
mRNA-1273 vaccination substudy is designed to assess safety, reactogenicity, and 
immunogenicity through 12 months post third vaccination (Substudy Day 366). Subjects who 
pariticpiate in this substudy are from the same three domestic clinical research sites that enrolled 
into the main study. 
Table 13: Treatment Arms and Substudy Dosing 
Cohort 
Sample 
Size** 
Stratum 
(Years of Age) 
First and Second Dose 
in Main Study 
Optional Third Dose 
in Substudy 
1 
15 
18-55 
25 mcg mRNA-1273 
100 mcg mRNA-1273 
2 
15 
18-55 
100 mcg mRNA-1273 
100 mcg mRNA-1273 
3 
15 
18-55 
250 mcg mRNA-1273 
100 mcg mRNA-1273 
4 
10 
56-70 
25 mcg mRNA-1273 
100 mcg mRNA-1273 
5 
10 
56-70 
100 mcg mRNA-1273 
100 mcg mRNA-1273 
6* 
10 
56-70 
250 mcg mRNA-1273 
n/a 
7 
10 
≥71 
25 mcg mRNA-1273 
100 mcg mRNA-1273 
8 
10 
≥71 
100 mcg mRNA-1273 
100 mcg mRNA-1273 
9* 
10 
≥71 
250 mcg mRNA-1273 
n/a 
10 
15 
18-55 
50 mcg mRNA-1273 
100 mcg mRNA-1273 
11 
10 
56-70 
50 mcg mRNA-1273 
100 mcg mRNA-1273 
12 
10 
≥71 
50 mcg mRNA-1273 
100 mcg mRNA-1273 
13* 
15 
18-55 
10 mcg mRNA-1273 
n/a 
*Cohorts 6, 9 and 13 were not enrolled. 
***Four subjects did not receive the second dose of mRNA-1273 in the main study. Three 
subjects discontinued due to an AE (hives on lower extremities judged related to the first 
mRNA-1273 vaccination [cohort 1], sore throat [cohort 3], and maculopapular rash [cohort 5]); 
the other subject discontinued treatment due to quarantine for a COVID-19 exposure (cohort 1). 
The third mRNA-1273 vaccination will be offered to subjects who received 2 doses of 25 or 50 
mcg (cohorts 1, 4, 7, 10, 11, and 12), which are lower than the EUA mRNA-1273 dosage of 100 

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mcg, as soon as feasible after their Main Study Day 209 visit, and also will be offered to subjects 
who received 2 doses of 100 and 250 mcg (cohorts 2, 3, 5, and 8) no later than the close of the 
window for their originally scheduled Main Study Day 394 visit. 
Subjects who receive the third mRNA-1273 vaccination will exit the Schedule of Activities for 
the main study and will enter the Schedule of Activities for the optional third mRNA-1273 
vaccination substudy (see Table 14). Substudy follow-up visits will occur 1, 2 and 4 weeks post 
the third mRNA-1273 vaccination (Substudy Days 8, 15, and 29), as well as 3, 6 and 12 months 
after the third mRNA-1273 vaccination (Substudy Days 91, 181 and 366). Blood will be drawn 
at these substudy visits for immunogenicity assays. As with prior mRNA-1273 vaccinations, 
reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of the third mRNA-1273 vaccination through 7 days after the third 
mRNA-1273 vaccination. Unsolicited non-serious AEs will be collected from the time of the 
third mRNA-1273 vaccination through 28 days after the third mRNA-1273 vaccination. SAEs, 
Protocol Specified AESIs, MAAEs, and NOCMCs will be collected from the time of first 
mRNA-1273 vaccination through 12 months after the third mRNA-1273 vaccination. 
Subjects who do not participate in this substudy, including those who are not eligible to 
participate in the substudy due to their prior receipt of an FDA authorized (under an EUA) or 
approved COVID-19 vaccine outside of this clinical trial, will continue, with their permission, to 
be followed according to the Schedule of Activities for the main study (see Table 4). 
Interim safety and immunogenicity data from this substudy may be reviewed as needed, at the 
discretion of the study team, to inform public health decisions and to assess the adequacy of the 
immune responses in the 25 and 50 mcg dose cohorts compared with the 100 mcg dose cohort. 
Information from interim data reviews may be disseminated to public health officials and 
partners as needed and included in publications and presentations to inform the global scientific 
community. 
Evaluation of immunogenicity will include quantitation of antibodies to the SARS-CoV-2 S 
protein at multiple timepoints post third mRNA-1273 vaccination as measured by ELISA and 
virus neutralization assays. In addition, exploratory studies to characterize T cell responses are 
planned. 
Subjects who participate in the optional third mRNA-1273 vaccination substudy will exit the 
Schedule of Activities for the main study between Visit 13 and the close of the window for Visit 
14 and will not have Visit 14, instead will have Visit 14A and subsequent substudy visits (see 
Table 14). 

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Table 14: Schedule of Activities for the Optional Third mRNA-1273 Vaccination Substudy 
Optional Third mRNA-1273 
Vaccination Substudy Schedule Day 
D1 
D8 
D15 
D29 D91 D181 D366 
SubStudy Visit Window (± number of 
days) 
n/a 
2d 
2d 
4d 
10d 
12d 
30d 
Optional Third mRNA-1273 
Vaccination Substudy Visit 
V14A 
V15 
V16 
V17 V18 
V19 
V20 
Clinical Evaluations and 
Procedures 
Tube 
 
 
 
 
 
 
 
Review eligibility criteria for the 
third mRNA-1273 vaccination 
 
X 
 
 
 
 
 
 
Review medical history and con 
meds 
 
X 
X 
X 
X 
X 
X 
X 
Vital signs 
 
X 
X 
X 
X 
{X} 
{X} 
{X} 
Third mRNA-1273 
Vaccination1 
 
X 
 
 
 
 
 
 
Targeted physical exam 
 
{X} 
{X} 
{X} 
{X} 
{X} 
{X} 
{X} 
Evaluate vaccination site 
 
X 
X 
 
 
 
 
 
Review memory aid 
 
 
X 
 
 
 
 
 
Solicited AEs 
 
X 
X 
 
 
 
 
 
Unsolicited AEs and SAEs 
 
X 
X 
X 
X2 
X2 
X2 
X2 
Pregnancy test (urine)3 
 
X 
 
 
 
 
 
 
Serum for humoral 
immunogenicity assays (mL) 
SST 
24 
24 
24 
24 
24 
24 
24 
Serum for secondary research 
(mL) 
SST 
8 
8 
8 
8 
8 
8 
8 
PBMC isolation for cellular 
immunology assays and plasma 
(mL) 
NaCit 
CPT 
40 
 
30 
30 
30 
30 
40 
PBMC isolation and plasma for 
secondary research 
NaCit 
CPT 
48 
40 
18 
34 
34 
34 
40 
Total volume per visit (mL) 
 
120 
72 
80 
96 
96 
96 
112 
Maximum cumulative blood 
volume4 (mL) (prior 56 days) 
 
192 
264 
344 
440 
96 
96 
112 
{ } Required at this substudy visit only if clinically indicated. 
1) 0.5 mL of the mRNA-1273 vaccine will be injected IM in the deltoid muscle. After the 
injection, subjects will be observed for 60 minutes. The injection site will be evaluated, and 
vital signs obtained, during that period and before the subject leaves the clinic. 
2) After Substudy Day 29 through the end of the substudy (Substudy Day 366), only SAEs, 
Protocol Specified AESIs, MAAEs, and NOCMCs will be reported as AEs. 
3) For women of childbearing potential. Must be confirmed as negative prior to the third 
mRNA-1273 vaccination. The visit will also include review of contraceptive/menstrual 
history and pregnancy avoidance counselling. 

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4) For purposes of estimating the maximum possible cumulative blood volume over the prior 56 
days, this calculation assumes that the blood draw (72 mL) for Main Study Day 209 occurs 
on the day prior to Substudy Day 1. 
12.6 
Eligibility Criteria 
12.6.1 
Inclusion Criteria 
A subject must meet all the following criteria to be eligible to participate in this substudy: 
1. Enrolled in the main study and received both the first and second mRNA-1273 
vaccinations. 
2. Provides written informed consent for the third mRNA-1273 vaccination. 
3. Agrees to the collection of venous blood per substudy. 
4. Must agree to have samples stored for secondary research. 
5. Women of childbearing potential have had a negative urine pregnancy test within 24 
hours before the third mRNA-1273 vaccination. 
6. Women of childbearing potential1 must agree to use or have practiced true abstinence2 or 
use at least one acceptable primary form of contraception.3,4 
Note: These criteria are applicable to females in a heterosexual relationship and child-
bearing potential (i.e., the criteria do not apply to subjects in a same sex relationship). 
1Not of childbearing potential – post-menopausal females (defined as having a history of 
amenorrhea for at least one year) or a documented status as being surgically sterile 
(hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure® 
placement). 
2True abstinence is 100% of time no sexual intercourse (male’s penis enters the female’s 
vagina). (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation 
methods] and withdrawal are not acceptable methods of contraception). 
3Acceptable forms of primary contraception include monogamous relationship with a 
vasectomized partner who has been vasectomized for 180 days or more prior to the 
subject’s first vaccination, intrauterine devices, birth control pills, and 
injectable/implantable/insertable hormonal birth control products. 
4Must use at least one acceptable primary form of contraception for at least 30 days 
prior to the third mRNA-1273 vaccination and for at least 30 days after the third mRNA-
1273 vaccination. 
12.6.2 
Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from participation in this 
substudy. 
1. Anaphylaxis or other systemic hypersensitivity reaction following a mRNA-1273 or any 
other vaccination. 
2. Immediate allergic reaction of any severity after mRNA-1273 or any of its components.5 

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5Including polyethylene glycol (PEG) 
3. Immediate allergic reaction of any severity to polysorbate.6 
6Due to potential cross-reactive hypersensitivity with the vaccine ingredient PEG 
4. History of an SAE judged related to mRNA-1273 vaccine. 
5. Female subject who is breastfeeding or plans to breastfeed from the time of the third 
mRNA-1273 vaccination through 30 days after the third mRNA-1273 vaccination. 
6. Has an acute illness7, as determined by the participating site PI or appropriate sub-
investigator, with or without fever [oral temperature ≥38.0°C (100.4°F)], within 72 hours 
prior to the third mRNA-1273 vaccination. 
7An acute illness which is nearly resolved with only minor residual symptoms remaining 
is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, 
the residual symptoms will not interfere with the ability to assess safety parameters as 
required by the substudy. 
7. Has received any approved, authorized or investigational COVID-19 vaccine outside of 
this trial. 
8. Any clinically significant medical condition that, in the opinion of the investigator, poses 
an additional risk to the subject from vaccination. 
9. History of documented COVID-19 infection. 
10. Has any medical disease or condition that, in the opinion of the participating site PI or 
appropriate sub-investigator, precludes substudy participation. 
11. Received or plans to receive a licensed vaccine, other than a COVID-19 vaccine, within 2 
weeks before or after the third mRNA-1273 vaccination. 
12.7 
Study Product 
12.7.1 
Study Product Description 
Product: mRNA-1273 
For the optional third mRNA-1273 vaccination substudy, mRNA-1273 is provided by 
ModernaTX, Inc. via the DMID CMS as a sterile solution for injection in a 10 dose multidose 
vial formulated at a concentration of 0.2mg/mL in 20 mM Tris buffer containing 87 mg/mL 
sucrose and 4.3 mM acetate, at pH 7.5 and presented in 10R USP Type I borosilicate glass vials 
with PLASCAP vial seal containing a 20 mm FluroTec-coated plug stopper and aluminum flip-
off crimp seals with a nominal fill volume of 6.3 mL/vial. 
There is no preservative in the mRNA-1273 solution. Hence, all ten (10) doses must be 
withdrawn into individual dosing syringes in quick succession, one after the other once the vial is 
breached. 
Dilution is not required for the third mRNA-1273 vaccination. Each multidose vial contains 
ready-to-use solution and does not require further dilution or preparation. It will be administered 
as a single 0.5 mL IM injection of 100 mcg into the deltoid muscle. 

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See the protocol-specific MOP for detailed information: 
• 20 (minimum) to 30 (maximum) minutes are required for the mRNA-1273 vials to 
equilibrate to room temperature (20ºC to 25ºC). 
• A maximum of 30 minutes is allowed between completion of equilibration and 
completion of dosing syringes fill. 
• Ten (10) dosing syringes must be prepared from each mRNA-1273 vial. 
• All dosing syringes must be filled in quick succession, one after the other. 
• Filled dosing syringes must be held at room temperature (20ºC to 25ºC) and will expire 
(eight) 8 hours after being filled. 
• Withdrawal of mRNA-1273 from the vial into the dosing syringes should be completed 
within 30 minutes after the vial has equilibrated to room temperature (20ºC to 25ºC). 
12.7.2 
Dose Modifications 
It is unknown whether subjects in the 25 mcg and 50 mcg cohorts from the main study have been 
optimally primed to respond to the third mRNA-1273 vaccination. In the event that the responses 
to a third mRNA-1273 vaccination in either or both of those cohorts are judged to be suboptimal 
in comparison to the responses in the 100 mcg cohorts, the study team will inform the subjects 
and consider a protocol amendment to administer another mRNA-1273 vaccination at a dosage 
of 100 mcg. 
12.7.3 
Product Storage and Stability 
Product: mRNA-1273 
For the optional third mRNA-1273 vaccination substudy, mRNA-1273 must be stored in a secure 
area with limited access (pharmacy staff only), and must be stored locally under refrigerated 
conditions (2°C to 8°C [36°F to 46°F)]. The refrigerator should have an automated temperature 
recording and alert system. There must be an available back-up refrigerator. The refrigerators 
must be connected to a back-up generator; or alternate plan in the event of a power failure. The 
pharmacy must have in place a 24-hour alert system that allows for rapid response in case of 
refrigerator malfunctioning. 
Prepared doses should remain at ambient temperatures (20ºC to 25ºC) and should not be shaken 
or allowed to roll during transport. Avoid exposing to direct sunlight while the syringe is in route 
to the injection administration location. If the prepared doses require transportation to a separate 
facility, ensure there are appropriate transport procedures in place. Under all circumstances, the 
time from preparation, transportation and administration of mRNA-1273 must occur within 
maximum (nine) 9 hours from the time the vials are removed from the refrigerator. 
• A minimum of 20 minutes and a maximum of 30 minutes are allowed for equilibration of 
vial to room temperature (20°C to 25°C) after removal from refrigerator. 
• A maximum of 30 minutes is allowed between completion of equilibration and 
completion of dosing syringes fill. However, all dosing syringes (10) must be filled in 
quick succession once the vial is breached. 

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• A maximum of 8 (eight) hours is allowed for holding dosing solution in dosing syringes 
prior to completion of administration. 
• Note that the multi-dose vial does not contain a preservative and must be discarded 6 
hours after the first penetration of the sterile septum. 
12.8 
Concomitant Therapy 
Information about prior medications, including hormonal contraceptives, taken by the subject in 
the 30 days prior to providing informed consent for the substudy will be recorded on the 
appropriate DCF. 
Concomitant medications include all medications (prescription, over the counter, supplements, 
and vaccines received outside of the study) taken by the subject from the time the substudy 
informed consent is signed through Substudy Day 366. At each substudy visit following the third 
mRNA-1273 vaccination, subjects will be queried about new concomitant medications and 
changes to existing medications. 
Medications that might interfere with the evaluation of the investigational product should not be 
used by the subject during the study-reporting period (12 months after the third mRNA-1273 
vaccination) unless clinically indicated as part of the subject’s health care. 
In the event medical conditions dictate the use of medications, subjects are encouraged to obtain 
adequate care, comply with the course of therapy as prescribed by their physician, and inform the 
study Investigator as soon as practical. Any drug or vaccine used or received by the subject 
during the study-reporting period (12 months after the third mRNA-1273 vaccination) should be 
recorded on the appropriate DCF. 
12.9 
Immunogenicity Evaluations 
Serological Immunogenicity Assays: 
The following serological immunogenicity assays may be performed on specimens collected on 
the day of and following the third mRNA-1273 vaccination: 
• IgG ELISA to the SARS-CoV-2 S (spike) protein(s) and SARS-CoV-2 N protein. 
• Pseudovirus and live SARS-CoV-2 neutralization assays. 
Cellular Immunology Assays: 
This substudy will also investigate T cell immune responses using multiparametric flow 
cytometry. 
The volume of venous blood to be collected at each substudy visit for immunogenicity 
evaluations is presented in Table 14. 
12.10 
Adverse Events and Serious Adverse Events 
12.10.1 
Reporting of Adverse Events 
Reporting of all AEs, solicited and unsolicited, will occur during the period from administration 
of the third mRNA-1273 vaccine on Substudy Day 1 through Substudy Day 29. 

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Solicited AEs (i.e., reactogenicity) will be collected using a memory aid and recorded on the 
appropriate DCF from the time of the third mRNA-1273 vaccination through 7 days post third 
mRNA-1273 vaccination (Substudy Days 1-8). 
Unsolicited AEs of all severities will be reported from the time of the third mRNA-1273 
vaccination on Substudy Day 1 through Substudy Day 29. 
After Substudy Day 29 through the end of the substudy (Substudy Day 366), only SAEs, 
Protocol Specified AESIs, MAAEs, and NOCMCs will be reported as AEs. 
SAEs, Protocol Specified AESIs, MAAEs, and NOCMCs will be collected from Substudy Day 1 
through the end of the substudy (Substudy Day 366). 
12.10.2 
Reporting of Pregnancy 
Pregnancy is not an AE. However, any pregnancy that occurs during substudy participation 
(through Substudy Day 366 post third mRNA-1273 vaccination) should be reported to the 
sponsor on the appropriate DCF. Pregnancy should be followed to outcome. 
12.10.3 
Unanticipated Problem Reporting 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
▪ UPs that are SAEs will be reported to the IRB and to the SDCC/study sponsor within 24 
hours of the participating site PI or appropriate sub-investigator becoming aware of the 
event per the above described SAE reporting process. 
▪ UPs that are SAEs will be collected from Substudy Day 1 through the end of the substudy 
(Substudy Day 366). 
▪ Any other UP will be reported to the IRB and to the SDCC/study sponsor within 3 days 
of the participating site PI or appropriate sub-investigator becoming aware of the 
problem. 
▪ UPs that are not SAEs will be collected from Substudy Days 1-29. 
12.11 
Statistical Considerations 
12.11.1 
Statistical Hypotheses 
This is a substudy to a phase I, open-label, dose-ranging clinical trial and is not designed to test a 
specific hypothesis. Rather, it is intended to obtain preliminary estimates in healthy adults of the 
safety, reactogenicity, and immunogenicity of a third mRNA-1273 vaccination between 6 
months and 12 months post second mRNA-1273 vaccination. 
12.11.2 
Sample Size Determination 
Rare AEs are not demonstrable in a clinical study of this size; however, the probabilities of 
observing one or more AEs given various true event rates are presented in Table 9 and apply to 
the substudy as well. Statistical assumptions described in Section 9.2 apply to the substudy as 
well. It is possible that not all subjects will receive a third mRNA-1273 vaccination, assuming 5 
subjects in a cohort receive a third mRNA-1273 vaccination the chance of observing at least one 

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AE of probability 20% or more is approximately 67%. Assuming all subjects receive a third 
mRNA-1273 vaccination the following additional statistical consideration applies. With 120 
subjects across all cohorts the chance of observing at least one AE of probability 3% or more is 
approximately 97%. 
12.11.3 
Populations for Analyses 
The Safety Analysis population includes all subjects who received the third mRNA-1273 
vaccination. 
The modified intent-to-treat (mITT) population includes all subjects who received of the third 
mRNA-1273 vaccination and contributed both pre- and at least one post-third mRNA-1273 
vaccination venous blood samples for immunogenicity testing for which valid results were 
reported. 
In the final analysis, protocol deviations will be reviewed to determine which protocol deviations 
may affect the analysis. The per protocol (PP) population will then be defined – and this includes 
all subjects in the mITT subset with the following exclusions: 
• 
Data from all available visits for subjects found to be ineligible at the time of the third 
mRNA-1273 vaccination. 
• 
Data from all substudy visits subsequent for the protocol deviations that are considered to 
affect the science. 
• 
Data from any substudy visit that occurs substantially out of window. 
12.11.4 
Statistical Analyses 
Interim analyses of safety, reactogenicity, and immunologic response data may be done, as 
needed. 
The final substudy analysis will be performed after the final data lock (through Substudy Day 
366) and reported as an addendum to the clinical study report (CSR). The addendum will be 
completed when all primary safety endpoint data and all secondary immunogenicity endpoint 
data are available and received by the SDCC. Any available data from the exploratory 
immunogenicity endpoints may also be included in the addendum. Remaining exploratory 
immunogenicity endpoint data may be included in a further addendum to the CSR, publication of 
manuscript(s), or other report(s). Abbreviated analysis plans that describe planned analyses to 
facilitate dissemination of study data for public health reasons, including manuscript 
publication(s), will be developed by the SDCC. A full statistical analysis plan (SAP) will be 
developed by the SDCC and finalized prior to the final data lock. 
12.11.5 
General Approach 
Unless otherwise noted in the SAP, continuous variables will be summarized using the following 
descriptive statistics: n (non-missing sample size), mean, standard deviation, median, maximum 
and minimum. The frequency and percentages (based on the non-missing sample size) of 
observed levels will be reported for all categorical measures. 
12.11.6 
Analysis of the Primary Endpoint(s) 

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Section 12.11.8 describes the analyses of Safety which is the primary endpoint of this substudy. 
12.11.7 
Analysis of the Secondary Endpoint(s) 
Summaries and analysis of immunogenicity data will be presented for the mITT population. If 
there are protocol deviations which may affect the analysis, a per-protocol (PP) analysis may 
also be performed. 
GMFR and seroconversion analyses will be done using two definitions of baseline. Baseline 1 
will be considered Main Study Day 1 prior to the first mRNA-1273 vaccination (pre-first 
mRNA-1273 dose baseline) and baseline 2 will be considered Substudy Day 1 prior to the third 
mRNA-1273 vaccination (pre-third mRNA-1273 dose baseline). 
Seroconversion is defined as a 4-fold increase in antibody titer over baseline.  
Seroconversion rates, GMFR and GMT for SARS-CoV-2 as measured by IgG ELISA will be 
calculated at Substudy Days 1, 8, 15, 29, 91, 181 and 366 post third mRNA-1273 vaccination by 
cohort and will be summarized graphically. Seroconversion rates, GMFR and GMT will be 
presented with their corresponding 95% confidence interval (CI) estimates at each post-
vaccination timepoint and overall peak GMT. 
12.11.8 
Safety Analyses 
Summaries and analysis of safety data will be presented for the Safety Analysis Population. 
Solicited AEs will be summarized by severity for each day post third mRNA-1273 vaccination 
(Substudy Days 1-8) and as the maximum severity over all 8 days. Additionally, solicited AEs 
will be analyzed by taking the most severe response over the follow-up period and using 
standard techniques, such as exact confidence intervals (CI), to summarize the proportion of 
subjects reporting each symptom, any application site symptom, and any systemic symptom. 
Unsolicited non-serious AEs will be collected from the time of the third mRNA-1273 
vaccination through 28 days after the third mRNA-1273 vaccination. Unsolicited AEs will be 
coded by MedDRA for preferred term and system organ class (SOC). SAEs, Protocol Specified 
AESIs, MAAEs, and NOCMCs will be collected from the time of first mRNA-1273 vaccination 
through 12 months after the third mRNA-1273 vaccination. The numbers of SAEs and MAAEs 
will be reported by detailed listings showing the event description, MedDRA preferred term and 
SOC, relevant dates (vaccinations and AEs), severity, relatedness, and outcome for each event. 
Non-serious unsolicited AEs will be summarized as number and percentage of subjects reporting 
at least one event in each MedDRA preferred term and SOC, cross tabulated by severity and 
relationship to study product. Additionally, the proportion of subjects and exact 95% CIs of AEs 
in aggregate and by MedDRA categories will be computed. 
Clinical laboratory data will be summarized by severity for each substudy visit, and as the 
maximum over all post-vaccination substudy visits. Graphical presentations may include box 
plots and shift plots. 
12.11.9 
Baseline Descriptive Statistics 
Summaries of demographic variables such as age, sex, ethnicity, and race will be presented by 
cohort and overall. Summaries of baseline clinical laboratory values will be presented by cohort 
and overall. 

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12.11.10 Planned Interim and Early Analyses 
Data may be disseminated to public health officials and partners as needed and included in 
publications and presentations to inform the global scientific community.  
Cumulative safety information, study status, and primary endpoint results may be published, 
presented at a public forum, or presented as summaries aggregated by study arm at the discretion 
of the sponsor while the main study is ongoing. Any ad-hoc analyses, jointly developed by the 
SDCC and/or the VRC, other participating laboratories and ModernaTX, Inc., will be executed 
by the SDCC as needed. None of the interim analyses will include any formal statistical 
hypothesis testing; therefore, p value adjustment will not be made to any analyses. 
12.11.10.1 Interim Safety Analyses 
Given the need for rapid review and dissemination of study data for public health reasons, AEs 
and SAEs maybe reviewed as necessary outside of SMC reviews. The SMC will not need to 
meet (unless halting rules are met), and materials will be provided electronically. Documentation 
of review and any concerns noted will be solicited electronically. 
12.11.10.2 Interim Immunogenicity Review 
For public health reasons there may be several immunogenicity reviews as needed. 
Data may be disseminated to public health officials and partners as needed and included in 
publications and presentations to inform the global scientific community. 
12.11.10.3 Interim Immunogenicity and Safety Review 
Interim analyses of safety, reactogenicity, and immunologic response data may be done, as 
needed. 
12.11.11 Sub-Group Analyses 
The protocol does not define any formal subgroup analyses, and the substudy is not adequately 
powered to perform subgroup analyses. 
12.11.12 Tabulation of Individual Subject Data 
In general, all data will be listed, sorted by cohort and subject, and when appropriate by substudy 
visit number within subject. 
12.11.13 Exploratory Analyses 
Summaries and analysis of immunogenicity data will be presented for the mITT population. If 
there are protocol deviations which may affect the analysis, a PP analysis may also be 
performed. 
GMFR and seroconversion analyses will be done using two definitions of baseline. Baseline 1 
will be considered Main Study Day 1 prior to the first mRNA-1273 vaccination (pre-first 
mRNA-1273 dose baseline) and baseline 2 will be considered Substudy Day 1 prior to the third 
mRNA-1273 vaccination (pre-third mRNA-1273 dose baseline). 
Seroconversion is defined as a 4-fold increase in antibody titer over baseline.  

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Seroconversion rates, GMFR and GMT for SARS-CoV-2 as measured by IgG ELISA, 
neutralization assay using SARS-CoV-2 pseudovirus, neutralization assay using live SARS-
CoV-2, and multiplex assay IgG ELISA to the SARS-CoV-2 S proteins and SARS-CoV-2 N 
protein will be calculated for all post third mRNA-1273 timepoints by cohort and will be 
summarized graphically. Seroconversion rates, GMFR and GMT will be presented with their 
corresponding 95% CI estimates at each post-vaccination timepoint and overall peak GMT. 
Summaries and analysis of cellular assay data will be presented for the mITT population. If there 
are protocol deviations which may affect the analysis, a PP analysis may also be performed. 
The magnitude, phenotype and percentage of cytokine producing S protein-specific T cells will 
be summarized at each post-vaccination timepoint by vaccination group. 
12.12 
Regulatory, Ethical, and Study Oversight Considerations 
Informed consent for the substudy will be obtained in accordance with Section 10.1.1. 
As per Section 10.1.1.2, the rights and privacy of human subjects who participate in genomic or 
phenotypic research studies will be protected at all times. 
If subjects choose not to provide permission for extra blood and secondary research use, they 
will not be eligible for participation in the optional third mRNA-1273 vaccination substudy.  
Subjects may withdraw permission to use substudy samples for secondary use at any time. They 
will need to contact the participating site and the samples will be removed from the study 
repository after this substudy is completed and documentation will be completed that outlines the 
reason for withdrawal of permission for secondary use of samples. Subjects who withdraw 
consent before the last substudy visit will not have the extra blood drawn for secondary use.