Phase 1, Open-Label, Randomized Study of the Safety and Immunogenicity of a SARS-CoV-2 Variant Vaccine (mRNA-1273.351) in Naïve and Previously Vaccinated Adults
Phase: PHASE1
Conditions: COVID-19, COVID-19 Immunisation
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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Phase 1, Open-Label, Randomized Study of the Safety and Immunogenicity of a SARS-
CoV-2 Variant Vaccine (mRNA-1273.351) in Naïve and Previously Vaccinated Adults 
 
DMID Protocol Number: 21-0002 
 
IND Sponsor: Division of Microbiology and Infectious Diseases (DMID) 
 
Version Number: 3.0 
 
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 ...................................................................................................... 7 
1.1 
Synopsis .......................................................................................................................... 7 
1.2 
Schedule of Activities (SOA) ....................................................................................... 13 
2. 
INTRODUCTION ................................................................................................................ 16 
2.1 
Background and Study Rationale.................................................................................. 16 
 
Public Readiness and Emergency Preparedness Act ............................................ 17 
2.2 
Risk/Benefit Assessment .............................................................................................. 18 
 
Known Potential Risks .......................................................................................... 18 
 
Known Potential Benefits ..................................................................................... 20 
3. 
OBJECTIVES AND ENDPOINTS ...................................................................................... 20 
4. 
STUDY DESIGN.................................................................................................................. 21 
4.1 
Overall Design .............................................................................................................. 21 
4.2 
Scientific Rationale for Study Design........................................................................... 24 
4.3 
Justification for Doses................................................................................................... 24 
5. 
STUDY POPULATION ....................................................................................................... 26 
5.1 
Inclusion Criteria .......................................................................................................... 26 
5.2 
Exclusion Criteria ......................................................................................................... 27 
 
Exclusion of Specific Populations ........................................................................ 29 
5.3 
Inclusion of Vulnerable Subjects .................................................................................. 29 
5.4 
Lifestyle Considerations ............................................................................................... 30 
5.5 
Screen Failures .............................................................................................................. 30 
5.6 
Strategies for Recruitment and Retention ..................................................................... 30 
 
Recruitment ........................................................................................................... 30 
 
Retention ............................................................................................................... 30 
 
Compensation Plan for Subjects ........................................................................... 30 
 
Costs ...................................................................................................................... 30 
6. 
STUDY PRODUCT.............................................................................................................. 31 
6.1 
Study Product(s) and Administration............................................................................ 31 
 
Study Product Description .................................................................................... 31 
 
Dosing and Administration ................................................................................... 31 
 
Dose Modifications ............................................................................................... 32 
6.2 
Accountability/Handling/Storage/Preparation .............................................................. 32 
 
Acquisition and Accountability ............................................................................ 32 
 
Formulation and Appearance ................................................................................ 34 
 
Product Storage and Stability................................................................................ 34 
 
Preparation ............................................................................................................ 35 
6.3 
Measures to Minimize Bias: Randomization and Blinding .......................................... 35 
 
Treatment Assignment Procedures ....................................................................... 35 
 
Randomization and Blinding ................................................................................ 35 
 
Blinding and Masking Procedures ........................................................................ 36 

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6.4 
Study Intervention Compliance .................................................................................... 36 
6.5 
Concomitant Therapy.................................................................................................... 36 
 
Rescue Medicine ................................................................................................... 36 
 
Non-Research Standard of Care............................................................................ 36 
7. 
STUDY INTERVENTION DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL..................................................................................... 36 
7.1 
Pausing Criteria and Discontinuation of Study Intervention ........................................ 36 
 
Pausing Criteria ..................................................................................................... 36 
 
Criteria for Continuation of Dosing and Redosing ............................................... 37 
 
Discontinuation of Study Intervention .................................................................. 37 
7.1.3.1 
Delay of Study Vaccination .............................................................................. 37 
 
Follow-up for Subjects that Discontinued Study Intervention ............................. 38 
7.2 
Subject Withdrawal from the Study and Replacement ................................................. 38 
7.3 
Lost to Follow-Up ......................................................................................................... 39 
8. 
STUDY ASSESSMENTS AND PROCEDURES ................................................................ 39 
8.1 
Screening and Immunogenicity Assessments ............................................................... 39 
 
Screening or Enrollment/Baseline Procedures...................................................... 39 
 
Immunogenicity Evaluations ................................................................................ 40 
 
Samples for Genetic/Genomic Analysis ............................................................... 41 
8.1.3.1 
Genetic/Genomic Analysis ............................................................................... 41 
8.1.3.2 
Genetic Privacy and Confidentiality ................................................................. 41 
8.1.3.3 
Management of Results..................................................................................... 41 
8.2 
Safety and Other Assessments ...................................................................................... 41 
 
Procedures to be Followed in the Event of Abnormal Clinical Findings ............. 46 
8.3 
Adverse Events and Serious Adverse Events ............................................................... 46 
 
Definition of Adverse Event (AE) ........................................................................ 46 
8.3.1.1 
Solicited Adverse Events .................................................................................. 46 
8.3.1.2 
Unsolicited Adverse Events .............................................................................. 47 
8.3.1.3 
Special Reporting of Adverse Events ............................................................... 47 
 
Definition of Serious Adverse Event (SAE) ......................................................... 47 
 
Suspected Unexpected Serious Adverse Reactions (SUSAR).............................. 48 
 
Classification of an Adverse Event ....................................................................... 48 
8.3.4.1 
Severity of Adverse Events ............................................................................... 48 
8.3.4.2 
Relationship to Study Intervention ................................................................... 49 
 
Time Period and Frequency for Event Assessment and Follow-Up ..................... 49 
 
Adverse Event Reporting ...................................................................................... 49 
8.3.6.1 
Investigators Reporting of AEs ......................................................................... 49 
 
Serious Adverse Event Reporting ......................................................................... 49 
8.3.7.1 
Investigators Reporting of SAEs ...................................................................... 49 
8.3.7.2 
Regulatory Reporting of SAEs ......................................................................... 50 
 
Reporting Events to Subjects ................................................................................ 50 
 
Adverse Events of Special Interest (AESIs) ......................................................... 50 
 
Reporting of Pregnancy ........................................................................................ 51 
8.4 
Unanticipated Problems ................................................................................................ 52 

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Definition of Unanticipated Problems (UPs) ........................................................ 52 
 
Unanticipated Problem Reporting......................................................................... 52 
 
Reporting Unanticipated Problems to Subjects .................................................... 52 
9. 
STATISTICAL CONSIDERATIONS.................................................................................. 52 
9.1 
Statistical Hypotheses ................................................................................................... 52 
9.2 
Sample Size Determination........................................................................................... 52 
9.3 
Populations for Analyses .............................................................................................. 55 
9.4 
Statistical Analyses ....................................................................................................... 55 
 
General Approach ................................................................................................. 55 
 
Analysis of the Primary Endpoint(s)..................................................................... 55 
 
Analysis of the Secondary Endpoint(s)................................................................. 55 
 
Safety Analyses ..................................................................................................... 56 
 
Baseline Descriptive Statistics .............................................................................. 56 
 
Planned Interim and Early Analyses ..................................................................... 56 
9.4.6.1 
Interim Safety Analyses .................................................................................... 57 
9.4.6.2 
Interim Immunogenicity Review ...................................................................... 57 
9.4.6.3 
Interim Immunogenicity and Safety Review .................................................... 57 
 
Sub-Group Analyses ............................................................................................. 57 
 
Tabulation of Individual Subject Data .................................................................. 57 
 
Exploratory Analyses ............................................................................................ 57 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ....... 58 
10.1 
Regulatory, Ethical, and Study Oversight Considerations............................................ 58 
 
Informed Consent Process .................................................................................... 58 
10.1.1.1 
Requirements for Permission by Parents/Guardians and Assent by Children 
(in case of a minor) ........................................................................................................... 59 
10.1.1.2 
Other Informed Consent Procedures ............................................................. 59 
 
Study Termination and Closure ............................................................................ 61 
 
Confidentiality and Privacy .................................................................................. 61 
 
Secondary Use of Stored Specimens and Data ..................................................... 62 
10.1.4.1 
Samples for Secondary Research .................................................................. 63 
10.1.4.2 
Data Sharing for Secondary Research .......................................................... 63 
 
Key Roles and Study Governance ........................................................................ 64 
 
Safety Oversight.................................................................................................... 64 
10.1.6.1 
Safety Monitoring Committee (SMC) .......................................................... 64 
 
Clinical Monitoring ............................................................................................... 64 
 
Quality Control (QC) and Quality Assurance (QA) ............................................. 65 
 
Data Handling and Record Keeping ..................................................................... 65 
10.1.9.1 
Data Collection and Management Responsibilities ...................................... 65 
10.1.9.2 
Study Record Retention ................................................................................ 66 
10.1.9.3 
Source Records ............................................................................................. 66 
 Protocol Deviations ............................................................................................... 66 
 Publication and Data Sharing Policy .................................................................... 67 
 Human Data Sharing Plan ..................................................................................... 67 
 Genomic Data Sharing (GDS) Plan ...................................................................... 67 

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 Publication ............................................................................................................ 67 
 Conflict of Interest Policy ..................................................................................... 67 
10.2 
Additional Considerations ............................................................................................ 68 
 
Research Related Injuries ..................................................................................... 68 
10.3 
Abbreviations ................................................................................................................ 68 
10.4 
Protocol Amendment History ....................................................................................... 71 
11. REFERENCES ..................................................................................................................... 72 
12. APPENDIX A: Adverse Events of Special Interest (AESIs) Terms .................................... 75 
 
LIST OF TABLES 
Table 1. Cohort 1 Treatment Arms ................................................................................................. 8 
Table 2: Cohort 2 Treatment Arms ............................................................................................... 10 
Table 3: SOA for Cohort 1 (One Vaccination) ............................................................................. 13 
Table 4: SOA for Cohort 2: 2A-B (Three Vaccinations) .............................................................. 14 
Table 5: SOA for Cohort 2: 2C-H (Two Vaccinations) ................................................................ 15 
Table 6: Objectives and Endpoints (Outcome Measures)............................................................. 20 
Table 7. Cohort 1 Treatment Arms ............................................................................................... 22 
Table 8: Cohort 2 Treatment Arms ............................................................................................... 23 
Table 9: Venipuncture Volumes for Cohort 1 (One Vaccination) ................................................ 43 
Table 10: Venipuncture Volumes for Cohort 2: 2A-B (Three Vaccinations) .............................. 44 
Table 11: Venipuncture Volumes for Cohort 2: 2C-H (Two Vaccinations) ................................ 45 
Table 12: Probability of Observing an Adverse Event for Various Event Rates .......................... 54 
Table 13: Abbreviations ................................................................................................................ 68 
Table 14: Protocol Amendment History ....................................................................................... 71 
 
 
LIST OF FIGURES 
No table of figures entries found. 
 
 

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1. 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Rationale for Proposed Clinical Study 
The SARS Coronavirus 2 (SARS-CoV-2) pandemic has continued to intensify and as of January 
30, 2021, there are over 102 million cases and over 2 million deaths globally (Center for Systems 
Science and Engineering (CSSE) at Johns Hopkins University [systems.jhu.edu]). 
ModernaTX, Inc has developed a messenger RNA (mRNA)-based vaccine platform 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 used its mRNA-based technology to develop a 
novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine encoding for the spike (S) 
protein of the original Wuhan-Hu-1 isolate of SARS-CoV-2 (mRNA-1273) and in 2020 initiated 
Phase 1, Phase 2, and Phase 3 trials of a two-dose schedule of this vaccine, given 28 days apart, 
in adults, in the United States (Jackson LA et al, 2020; Anderson EJ et al, 2020; Widge AT et al, 
2020; Baden LR et al, 2020). The Phase 3 trial demonstrated 94.1% efficacy against 
symptomatic confirmed Coronavirus Disease 2019 (COVID-19) 14 days or later after the second 
vaccination and 100% efficacy against severe COVID-19 (Baden LR et al, 2020). On December 
18, 2020 the U.S. Food and Drug Administration issued an emergency use authorization (EUA) 
for administration of the vaccine to adults in the United States. 
Recently, SARS-CoV-2 variants with mutations in the S protein have emerged. A variant first 
identified in South Africa (B.1.351) is associated with increased transmission, higher viral 
burden, and possibly increased mortality in infected persons (Tegally H et al, 2020). To date, 
four SARS-CoV-2 vaccines, all based on the Wuhan-sequence of the S protein, have shown 
reduced activity against the B.1.351 variant (Wang P et al, 2021; Wu K et al, 2021). Sera from 
individuals vaccinated with mRNA-based vaccines had a 6-to-9-fold reduction in neutralizing 
activity against a B.1.351-matched pseudovirion relative to a Wuhan-matched pseudovirion. 
More recently, pivotal vaccine efficacy studies testing both viral vector and adjuvanted protein 
vaccines had lower efficacy in regions where B.1.351 was known to be circulating (Callaway E 
& Mallapaty S, 2021; Cohen J, 2021). 
There is an urgent need for vaccination strategies that induce broader protection that includes 
variants such as B.1.351 to decrease morbidity and mortality and reduce SARS-CoV-2 
transmission. ModernaTX, Inc, is developing a mRNA vaccine (mRNA-1273.351) that is similar 
to the mRNA-1273 vaccine available under the EUA, but in which the mRNA encodes for the S 
protein of the B.1.351 variant. 
This phase 1 clinical trial will evaluate the safety and immunogenicity of varying doses of 
mRNA-1273.351, given in vaccination schedules alone, in sequences with mRNA-1273, or as a 
combination vaccine that includes mRNA-1273, in adults 18 years of age and older who are 
either naïve to SARS-CoV-2 (have no history of COVID-19 disease or vaccination) or who have 
been previously vaccinated with mRNA-1273. 
Study Design 
This is a phase 1, open-label, randomized clinical trial in males and non-pregnant females, 18 
years of age and older, who are in good health, have no known history of COVID-19 or SARS-
CoV-2 infection, and meet all other eligibility criteria. This clinical trial is designed to assess the 

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safety, reactogenicity and immunogenicity of mRNA-1273.351 manufactured by ModernaTX, 
Inc, given in vaccination schedules alone, sequentially, or coadministered with mRNA-1273. 
mRNA-1273.351 is a novel LNP-encapsulated mRNA-based vaccine that encodes for a full-
length, prefusion stabilized S protein of the SARS-CoV-2 B.1.351 variant. Enrollment will occur 
at approximately five domestic clinical research sites. 
This study includes two cohorts. Cohort 1 will provide rapid information about the 
immunogenicity of mRNA-1273.351 in a previously vaccinated group. This cohort can inform 
near term public health decisions if the variant virus becomes more widespread. Cohort 2 will 
evaluate different strategies for generation of cross protective immune responses in a naïve 
population. This cohort will take longer to provide information on the immunogenicity of 
mRNA-1273.351, but is important to inform future public health strategies. As Cohorts 1 and 2 
are in different populations, they can be enrolled in parallel as determined by each site. 
Cohort 1 will include subjects 18 years of age and older who received two vaccinations of 
mRNA-1273 at dosages of 50 mcg, 100 mcg, or 250 mcg in the Phase 1 clinical trial (DMID 20-
0003). Those subjects will be offered enrollment into this study approximately 9 to 12 months 
after they received the second vaccination in DMID 20-0003. At enrollment in this study, their 
long-term follow-up in DMID 20-0003 will be terminated. Subjects will be randomized, within 
each of the DMID 20-0003 cohorts (age and dosage groups – 50 mcg, 100 mcg, and 250 mcg), 
1:1 (as outlined in Table 1) to either: 
• Arm 1A, vaccination with a 50-mcg dose of the mRNA-1273.351 variant, or 
• Arm 1B, vaccination with a combination vaccination that includes 25 mcg of mRNA-
1273 and 25 mcg of mRNA-1273.351. 
The anticipated sample size to be drawn from the DMID 20-0003 study population is 
approximately 45 subjects 18 through 55 years of age and approximately 20 subjects 56 years of 
age and older. 
Subjects in Cohort 1 will receive a single intramuscular (IM) injection of the designated vaccine 
and will be followed through 12 months after vaccination. Follow-up visits will occur on Days 8, 
15, and 29, as well as 3, 6, and 12 months after the vaccination. 
Table 1. Cohort 1 Treatment Arms 
Arm 
Sample Size 
Vaccination 
Product and Dose 
1A 
~30 
50 mcg mRNA-1273.351 
1B 
~30 
25 mcg mRNA-1273 
+ 25 mcg mRNA-1273.351 
Cohort 2 will include approximately 150 participants 18 through 55 years of age who have not 
received a COVID-19 vaccine, have no known history of COVID-19 or SARS-CoV-2 infection, 
and do not have underlying conditions that are associated with an increased risk of severe illness 
from SARS-CoV-2 infection. Enrollment may close before the full 150 participants based on 
estimates on the timing of immunogenicity results and the need to inform public health 
decisions. They will be randomly assigned to one of 8 treatment arms and will receive 2 or 3 IM 
injections of the vaccine (as outlined in Table 2), and followed through 12 months after the last 

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vaccination. Follow-up visits will occur 7, 14, and 28 days after each vaccination, as well as 3, 6 
and 12 months post the last vaccination. 

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Table 2: Cohort 2 Treatment Arms 
Arm 
Sample 
Size 
First Vaccination 
Second Vaccination 
Third Vaccination 
Product and Dose 
Interval 
Product and Dose 
Interval 
Product and Dose 
2A 
15 
100 mcg mRNA-1273 
28 days 
100 mcg mRNA-1273 
28 days 
50 mcg mRNA-
1273.351 
2B 
15 
50 mcg mRNA-1273 
28 days 
50 mcg mRNA-1273 
28 days 
50 mcg mRNA-
1273.351 
2C 
20 
100 mcg mRNA-1273.351 
28 days 
100 mcg mRNA-1273.351 
None 
2D 
20 
50 mcg mRNA-1273.351 
28 days 
50 mcg mRNA-1273.351 
None 
2E 
20 
100 mcg mRNA-1273 
28 days 
100 mcg mRNA-1273.351 
None 
2F 
20 
50 mcg mRNA-1273 
28 days 
50 mcg mRNA-1273.351 
None 
2G 
20 
50 mcg mRNA-1273 
+ 50 mcg mRNA-1273.351 
28 days 
50 mcg mRNA-1273 
+ 50 mcg mRNA-1273.351 
None 
2H 
20 
25 mcg mRNA-1273 
+ 25 mcg mRNA-1273.351 
28 days 
25 mcg mRNA-1273 
+ 25 mcg mRNA-1273.351 
None 
 
Summary of Treatment Arms: 
• 2A: Evaluates the mRNA1273 EUA vaccination series, plus a variant vaccine as a third dose. 
• 2B: Evaluates a 50-mcg vaccination series, plus a variant vaccine as a third dose. 
• 2C-2D: Evaluate 2 doses of the homologous variant vaccine at different dose levels. 
• 2E-2F: Evaluate heterologous prime-boost strategies at 2 dose levels. 
• 2G-2H: Evaluate a 1:1 mix of vaccine (2 doses), with the total dose for both vaccines equal to 100 mcg and 50 mcg, 
respectively. 
 

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For both Cohorts 1 and 2, reactogenicity will be assessed at the above-mentioned visits and 
blood will be drawn for immunogenicity assays. 
Objectives 
• Primary: To evaluate the safety and reactogenicity of mRNA-1273 and mRNA-1273.351 
vaccines, in naïve and previously vaccinated individuals. 
• Secondary: To assess humoral immunogenicity of mRNA-1273 and mRNA-1273.351 
vaccines, in naïve and previously vaccinated individuals. 
Inclusion Criteria 
See inclusion criteria in Section 5.1. 
Exclusion Criteria 
See exclusion criteria in Section 5.2. 
Study Phase 
• 1 
Study Population 
• Cohort 1, approximately 60 males and non-pregnant females 18 years of age and older, 
who are in good health and received two vaccinations of mRNA-1273 at dosages of 50 
mcg, 100 mcg or 250 mcg in DMID 20-0003. 
• Cohort 2, approximately 150 males and non-pregnant females, 18 through 55 years of 
age, who are in good health. 
Sites 
• Approximately five domestic clinical research sites. 
Study Intervention: 
• mRNA-1273 (0.2 milligrams [mg]/mL) 
• mRNA-1273.351 (0.5 mg/mL) 
• Each vaccine formulation will be diluted in 0.9% Sodium Chloride (NaCl) for injection, 
United States Pharmacopeia (USP). 
• Each dose will be administered via IM injection into the deltoid muscle. 
• For Cohort 2, Arms 2A-H, the second dose of vaccine will be administered preferably in 
the same arm used for the first dose. 
• For Cohort 2, Arms 2A and 2B, the third dose of vaccine will also be administered 
preferably in the same arm used for the first dose. 
Study Duration 
• The study duration is anticipated to be approximately 17 months (from start of screening 
through last subject last visit). 

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Subject Duration 
• The duration for each individual subject in Cohort 1 (from first contact to last visit) is 
approximately 13 months. 
• The duration for each individual subject in Cohort 2 (from first contact to last visit) is 
approximately: 
o 15 months for Arms 2A and 2B. 
o 14 months for Arms 2C through 2H. 
Safety 
• The study will use pausing rules for vaccinations in the study overall and for not 
administering second or third vaccinations to 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. 
 

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1.2 
Schedule of Activities (SOA) 
Table 3: SOA for Cohort 1 (One Vaccination) 
Study Day 
-42 to -1 
1 
8* 
15 
29 
91 
181 
366 
Unscheduled 
Visit 
Early 
Termination 
Visit 
Visit Window (±number of days) 
 
0 
1 
2 
2 
7 
7 
14 
 
 
Study Visit 
Screening 
(optional) 
00 
01 
02 
03 
04 
05 
06 
07 
 
 
Informed Consent 
X 
Xa 
 
 
 
 
 
 
 
 
Review Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
Xa 
 
 
 
 
 
 
 
 
Vaccination 
 
X 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
X 
X 
 
 
 
 
 
Interim History 
 
Xb 
 
X 
X 
X 
X 
X 
X 
X 
Symptom-Directed Physical 
Examination 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Vital Signsc 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
Height and Weight (for BMI) 
X 
Xa 
 
 
 
 
 
 
 
 
Pregnancy Testd 
 
X 
 
 
 
 
 
 
 
 
Memory Aid: Solicited AEs 
 
X 
X 
Xe 
 
 
 
 
 
 
Unsolicited AEs 
 
X 
X 
X 
X 
 
 
 
X 
X 
SAEs, Protocol Specified AESIs, 
MAAEs, and NOCMCs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum for Serological 
Immunogenicity Assays 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Peripheral Blood Mononuclear Cells 
(PBMCs) for Cellular Immunology 
Assays (and Plasma) 
 
X 
 
X 
 
 
X 
X 
 
X 
* Telephone call. 
a) If not performed at Visit 00. 
b) If medical history performed at Visit 00, then interim history at Visit 01. 
c) Vital signs to be obtained pre and post vaccination. Otherwise, only as clinically indicated. 
d) For women of childbearing potential, a negative urine pregnancy test on Day 1 with results confirmed prior to enrollment. 
e) Collect Memory Aid and assess for delayed onset local reactions. 
 

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Table 4: SOA for Cohort 2: 2A-B (Three Vaccinations) 
Study Day 
-42 to -1 
1 
8* 
15 
29 
36* 
43 
57 
64* 
71 
85 
147 
237 
422 
Unsc 
Visit 
Early 
Term 
Visit 
Visit Window (±number of days) 
 
0 
1 
2 
2 
1 
2 
2 
1 
2 
2 
7 
7 
14 
 
 
Study Visit 
Screening 
(optional) 
00 
01 
02 
03 
04 
05e 
06e 
07e 
08f 
09f 
10f 
11f 
12f 
13f 
 
 
Informed Consent 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Interim History 
 
Xb 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Symptom-Directed Physical 
Examination 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Vital Signsc 
 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Height and Weight (for BMI) 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Testd 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Memory Aid: Solicited AEs 
 
X 
X 
Xg 
X 
X 
Xg 
X 
X 
Xg 
 
 
 
 
 
 
Unsolicited AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
SAEs, Protocol Specified AESIs, 
MAAEs, and NOCMCs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum for Serological 
Immunogenicity Assays 
 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Peripheral Blood Mononuclear Cells 
(PBMCs) for Cellular Immunology 
Assays (and Plasma) 
 
X 
 
X 
X 
 
X 
X 
 
X 
 
 
X 
X 
 
X 
* Telephone call. 
a) If not performed at Visit 00. 
b) If medical history performed at Visit 00, then interim history at Visit 01. 
c) Vital signs to be obtained pre and post vaccination. Otherwise, only as clinically indicated. 
d) For women of childbearing potential, a negative urine pregnancy test on Day 1 with results confirmed prior to enrollment. 
e) Visits 05-07 windows should be based off the actual Visit 04 date. 
f) Visits 08-13 windows should be based off the actual Visit 07 date. 
g) Collect Memory Aid and assess for delayed onset local reactions. 
 

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Table 5: SOA for Cohort 2: 2C-H (Two Vaccinations) 
Study Day 
-42 to -1 
1 
8* 
15 
29 
36* 
43 
57 
119 
209 
394 
Unsc 
Visit 
Early 
Term 
Visit 
Visit Window (±number of days) 
 
0 
1 
2 
2 
1 
2 
2 
7 
7 
14 
 
 
Study Visit 
Screening 
(optional) 
00 
01 
02 
03 
04 
05e 
06e 
07e 
08e 
09e 
10e 
 
 
Informed Consent 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Review Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Vaccination 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Interim History 
 
Xb 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Symptom-Directed Physical Examination 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Vital Signsc 
 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Height and Weight (for BMI) 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Testd 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Memory Aid: Solicited AEs 
 
X 
X 
Xf 
X 
X 
Xf 
 
 
 
 
 
 
Unsolicited AEs 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
SAEs, Protocol Specified AESIs, 
MAAEs, and NOCMCs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum for Serological Immunogenicity 
Assays 
 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Peripheral Blood Mononuclear Cells 
(PBMCs) for Cellular Immunology 
Assays (and Plasma) 
 
X 
 
X 
X 
 
X 
 
 
X 
X 
 
X 
* Telephone call. 
a) If not performed at Visit 00. 
b) If medical history performed at Visit 00, then interim history at Visit 01. 
c) Vital signs to be obtained pre and post vaccination. Otherwise, only as clinically indicated. 
d) For women of childbearing potential, a negative urine pregnancy test on Day 1 with results confirmed prior to 
enrollment. 
e) Visits 05-10 windows should be based off the actual Visit 04 date. 
f) Collect Memory Aid and assess for delayed onset local reactions. 
 

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2. 
INTRODUCTION 
2.1 
Background and Study Rationale 
An outbreak of COVID-19 caused by a novel SARS-CoV-2 began in Wuhan, Hubei Province, 
China in December 2019, and the disease has since spread globally (WHO 2020a). The World 
Health Organization (WHO) declared COVID-19 a pandemic on 11 Mar 2020; however, 
widespread community transmission was already occurring in many locations. As of 14 Jan 
2021, more than 92 million cases and 1.9 million deaths worldwide have been attributed to the 
COVID-19 pandemic (JHU 2020; WHO 2020a). 
ModernaTX, Inc has developed a vaccine platform based on the principle and observations that 
cells in vivo can take up mRNA, translate it, and then express protein viral antigen(s) on the cell 
surface. mRNA is highly precise in its translation into proteins that match viral antigens. The 
delivered mRNA does not enter the cell nucleus or interact with the genome, is nonreplicating, 
and is expressed transiently. The estimated half-life for mRNA after injection is approximately 8 
to 10 hours, before degradation by native RNases in the body, but the duration of effect also 
depends on the half-life of the expressed protein, which persists in the body for several days. 
mRNA vaccines have been used to induce immune responses against infectious viral pathogens 
such as cytomegalovirus, human metapneumovirus, parainfluenza virus type 3, Zika, and 
influenza. 
The mRNA‑1273 encodes for the full-length spike (S) protein of SARS-CoV-2, modified to 
introduce 2 proline residues to stabilize the S protein (S-2P) in a prefusion conformation, derived 
from the Wuhan-Hu-1 strain (Corbett KS et al, 2020). The mRNA-1273 vaccine is currently 
being evaluated for safety and immunogenicity in a dose‑ranging Phase 1 study sponsored by 
DMID (NCT04283461), for safety and immunogenicity in a Moderna-sponsored Phase 2a study 
(NCT04405076), and for safety, efficacy, and immunogenicity in a Moderna‑sponsored Phase 3 
study (NCT04470427). All three of these studies are ongoing and conducted in the US. 
The primary efficacy objective of the Phase 3 study was met, with the vaccine efficacy of 
mRNA-1273 to prevent symptomatic COVID-19 disease observed to be 94.1%. The vaccine was 
also observed to be efficacious in preventing severe COVID-19. In December 2020 the FDA 
issued Emergency Use Authorization of mRNA-1273 (Moderna COVID-19 Vaccine) for active 
immunization to prevent COVID-19 in individuals 18 years of age and older. 
Recently, SARS-CoV-2 variants with mutations in the S protein have emerged. A variant first 
identified in South Africa (B.1.351) is associated with increased transmission, higher viral 
burden, and possibly increased mortality in infected persons (Tegally H et al, 2020). To date, 
four vaccines, all based on the Wuhan-sequence of the S protein, have shown reduced activity 
against the B.1.351 variant. Sera from individuals vaccinated with mRNA-based vaccines had a 
6-to-9-fold reduction in neutralizing activity against a B.1.351-matched pseudovirion relative to 
a Wuhan-matched pseudovirion (Wang P et al, 2021; Wu K et al, 2021). More recently, pivotal 
studies testing both viral vector and adjuvanted protein technologies had lower efficacy in 
regions where B.1.351 was known to be circulating (Callaway E & Mallapaty S; Cohen J, 2021). 
Hence, the development and testing of vaccines targeting this SARS-CoV-2 variant is urgently 
needed. 

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mRNA-1273.351, like mRNA-1273, encodes the prefusion stabilized S protein of SARS-CoV-2. 
However, the mRNA of mRNA-1273.351 incorporates the key mutations present in the B.1.351 
strain of the virus. This phase 1 clinical trial will evaluate the immunological benefit of boosting 
subjects previously vaccinated with mRNA-1273 (DMID 20-0003) with the B.1.351 strain-
specific S protein, as well as the breadth of response induced by vaccinating with mRNA-1273 
and mRNA-1273.351 in naïve persons, who have not previously received a SARS-CoV-2 
vaccine and are not known to have been previously infected with SARS-CoV-2. 
Results from this study will inform the design of subsequent clinical studies of mRNA-1273.351. 
Plans for further clinical development are being drafted in consultation with regulatory 
authorities by Moderna. This will include evaluation in a subsequent Phase 2/3 study that will 
assess the safety and immunogenicity of both monovalent mRNA-1273.351 and multivalent 
mRNA-1273/mRNA-1273.351. These studies will assess both single-dose boosting at different 
dose intervals than the current study and a two-dose primary series at different dose levels in 
larger numbers of study participants. 
 
Public Readiness and Emergency Preparedness Act 
The study vaccines, mRNA-1273 and mRNA-1273.351, 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 and mRNA-1273.351. 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 
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 

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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 
 
Known Potential Risks 
The potential risks of participating in this trial are those associated with having blood drawn, IM 
injection, possible reactions to the mRNA-1273 and mRNA-1273.351 vaccines, 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 mRNA-1273 and mRNA-1273.351 
Immediate systemic allergic reactions (e.g., anaphylaxis) can occur following any vaccination. 
These reactions are very rare and are estimated to occur once per 450,000 vaccinations for 
vaccines that do not contain allergens such as gelatin or egg protein (Zent O et al, 2002). 
Anaphylactic reactions have occurred after administration of the Moderna and the Pfizer mRNA 
COVID-19 vaccines in vaccination campaigns under Emergency Use Authorization (EUA) in 
the United States. Most of these reactions had onset within 30 minutes of vaccination, most of 
these events occurred in persons with a prior history of allergy, and nearly all were women. The 
currently estimated risk of an anaphylactic reaction to the Moderna EUA COVID-19 vaccine is 
about 3 events per million vaccinations. 
As a precaution, all subjects will remain under observation at the study site for at least 30 
minutes after injection. 
Infrequently, people who have received dermal fillers might experience swelling at or near the 
site of filler injection (usually face or lips) following administration of a dose of an mRNA 
COVID-19 vaccine. The swelling appears to be temporary and resolves with medical treatment, 
including corticosteroid therapy. COVID-19 vaccines can be administered to people who have 
received injectable dermal fillers who have no contraindications or precautions for vaccination. 

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Vasovagal syncope (fainting) can occur before or after any vaccination, is usually triggered by 
the pain or anxiety caused by the injection and is not related to the substance injected. Therefore, 
it is important that standard precautions and procedures be followed to avoid injury from 
fainting. 
Intramuscular injection with other mRNA vaccines manufactured by ModernaTX, Inc containing 
the SM-102 lipid formulation commonly results in a transient and self-limiting local 
inflammatory reaction. This typically includes pain, erythema (redness), or swelling (hardness) at 
the injection site, which are mostly mild to moderate in severity and usually occur within 24 
hours of injection. A small percentage of participants may experience late local inflammatory 
reactions, with onset seven or more days after, usually the first, vaccination, and characterized by 
redness in the deltoid area of the upper arm and/or pain or itching (Baden LR et al, 2020). These 
reactions are self-limited and are not a contraindication to subsequent vaccinations in the 
vaccination series. 
The majority of local and systemic solicited adverse events (AEs) observed after injection with 
mRNA-1273 at the 100-mcg dose level have been mild to moderate in severity. The most 
commonly reported systemic AEs were headache, myalgia, fatigue, chills, and fever (Baden LR 
et al, 2020). In the majority of cases, the reactions resolved spontaneously within several days. 
Laboratory abnormalities (including increases in liver function tests and serum lipase levels) 
following injection were observed in clinical studies with similar mRNA-based vaccines. These 
abnormalities were without clinical symptoms or signs and returned toward baseline, pre-
vaccination (Day 1) values over time. The clinical significance of these observations is unknown. 
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, 
tachycardia, or palpitations. Subjects will be encouraged to immediately contact research staff 
and their medical provider if these symptoms occur following a study vaccination.  
There is limited experience with administration of a third dose of the mRNA COVID-19 
vaccines, and it is possible that the third dose may be associated with more frequent or more 
severe adverse events. 
Further details are provided in the current IB for mRNA-1273. mRNA-1273.351 has not been 
tested clinically, but based on its similarity to mRNA-1273, the risks are expected to be similar. 
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 

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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 
federal laws provide protections against genetic discrimination. Researchers will need to 
maintain confidentiality in order to be granted access to genetic information. 
 
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. Data from the Phase 3 placebo-controlled clinical trial of mRNA-1273 demonstrated 
94.1% efficacy of the vaccine when 100 mcg is administered as a two-vaccination series versus 
placebo against SARS-CoV-2 infection. The efficacy of other dosages of mRNA-1273 (e.g., 25, 
50, or 250 mcg) is not known. The doses and vaccination strategies used in this trial may or may 
not alter this protection. It is unknown if the mRNA-1273.351 vaccine will provide protection 
against infection with the B.1.351 variant. 
3. 
OBJECTIVES AND ENDPOINTS 
Table 6: Objectives and Endpoints (Outcome Measures) 
OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
Primary 
 
• 
To evaluate the safety and reactogenicity 
of mRNA-1273 and mRNA-1273.351 
vaccines, in naïve and previously 
vaccinated individuals. 
• 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 

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OBJECTIVES 
ENDPOINTS 
(OUTCOME MEASURES) 
from the first vaccination through 12 
months after the last vaccination. 
Secondary 
 
• 
To assess humoral immunogenicity of 
mRNA-1273 and mRNA-1273.351 
vaccines, in naïve and previously 
vaccinated individuals. 
• 
Response rate, and magnitude of SARS-
CoV-2-specific antibody binding and 
neutralization titers in serum samples as 
assessed via a range of assays at all 
timepoints. 
Exploratory 
 
• 
To assess, in at least a subset of samples 
the innate immune response and B cell 
response following vaccination. 
• 
Magnitude, phenotype, and percentage of 
innate immune cells and SARS-CoV-2 
specific B cells, as measured by flow 
cytometry, and targeted B cell repertoire 
analysis at different timepoints post 
vaccination relative to baseline. 
• 
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. 
4. 
STUDY DESIGN 
4.1 
Overall Design 
This is a phase 1, open-label, randomized clinical trial in males and non-pregnant females, 18 
years of age and older, who are in good health, have no known history of COVID-19 or SARS-
CoV-2 infection, and meet all other eligibility criteria. This clinical trial is designed to assess the 
safety, reactogenicity and immunogenicity of mRNA-1273.351 manufactured by ModernaTX, 
Inc, given in vaccination schedules alone, sequentially, or coadministered with mRNA-1273. 
mRNA-1273.351 is a novel LNP-encapsulated mRNA-based vaccine that encodes for a full-
length, prefusion stabilized S protein of the SARS-CoV-2 B.1.351 variant. Enrollment will occur 
at approximately five domestic clinical research sites. 
This study includes two cohorts. Cohort 1 will provide rapid information about the 
immunogenicity of mRNA-1273.351 in a previously vaccinated group. This cohort can inform 
near term public health decisions if the variant virus becomes more widespread. Cohort 2 will 
evaluate different strategies for generation of cross protective immune responses in a naïve 
population. This cohort will take longer to provide information on the immunogenicity of 

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mRNA-1273.351, but is important to inform future public health strategies. As Cohorts 1 and 2 
are in different populations, they can be enrolled in parallel as determined by each site. 
Cohort 1 will include subjects 18 years of age and older who received two vaccinations of 
mRNA-1273 at dosages of 50 mcg, 100 mcg, or 250 mcg in the Phase 1 clinical trial (DMID 20-
0003). Those subjects will be offered enrollment into this study approximately 9 to 12 months 
after they received the second vaccination in DMID 20-0003. At enrollment in this study, their 
long-term follow-up in DMID 20-0003 will be terminated. Subjects will be randomized, within 
each of the DMID 20-0003 cohorts (age and dosage groups – 50 mcg, 100 mcg, and 250 mcg), 
1:1 (as outlined in Table 7) to either: 
• Arm 1A, vaccination with a 50-mcg dose of the mRNA-1273.351 variant, or 
• Arm 1B, vaccination with a combination vaccination that includes 25 mcg of mRNA-
1273 and 25 mcg of mRNA-1273.351. 
The anticipated sample size to be drawn from the DMID 20-0003 study population is 
approximately 45 subjects 18 through 55 years of age and approximately 20 subjects 56 years of 
age and older. 
Subjects in Cohort 1 will receive a single intramuscular (IM) injection of the designated vaccine 
and will be followed through 12 months after vaccination. Follow-up visits will occur on Days 8, 
15, and 29, as well as 3, 6, and 12 months after the vaccination. 
Table 7. Cohort 1 Treatment Arms 
Arm 
Sample Size 
Vaccination 
Product and Dose 
1A 
~30 
50 mcg mRNA-1273.351 
1B 
~30 
25 mcg mRNA-1273 
+ 25 mcg mRNA-1273.351 
Cohort 2 will include approximately 150 participants 18 through 55 years of age who have not 
received a COVID-19 vaccine, have no known history of COVID-19 or SARS-CoV-2 infection, 
and do not have underlying conditions that are associated with an increased risk of severe illness 
from SARS-CoV-2 infection. Enrollment may close before the full 150 participants based on 
estimates on the timing of immunogenicity results and the need to inform public health 
decisions. They will be randomly assigned to one of 8 treatment arms and will receive 2 or 3 IM 
injections of the vaccine (as outlined in Table 8), and followed through 12 months after the last 
vaccination. Follow-up visits will occur 7, 14, and 28 days after each vaccination, as well as 3, 6, 
and 12 months post the last vaccination. 
 

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Table 8: Cohort 2 Treatment Arms 
Arm 
Sample 
Size 
First Vaccination 
Second Vaccination 
Third Vaccination 
Product and Dose 
Interval 
Product and Dose 
Interval 
Product and Dose 
2A 
15 
100 mcg mRNA-1273 
28 days 
100 mcg mRNA-1273 
28 days 
50 mcg mRNA-
1273.351 
2B 
15 
50 mcg mRNA-1273 
28 days 
50 mcg mRNA-1273 
28 days 
50 mcg mRNA-
1273.351 
2C 
20 
100 mcg mRNA-1273.351 
28 days 
100 mcg mRNA-1273.351 
None 
2D 
20 
50 mcg mRNA-1273.351 
28 days 
50 mcg mRNA-1273.351 
None 
2E 
20 
100 mcg mRNA-1273 
28 days 
100 mcg mRNA-1273.351 
None 
2F 
20 
50 mcg mRNA-1273 
28 days 
50 mcg mRNA-1273.351 
None 
2G 
20 
50 mcg mRNA-1273 
+ 50 mcg mRNA-1273.351 
28 days 
50 mcg mRNA-1273 
+ 50 mcg mRNA-1273.351 
None 
2H 
20 
25 mcg mRNA-1273 
+ 25 mcg mRNA-1273.351 
28 days 
25 mcg mRNA-1273 
+ 25 mcg mRNA-1273.351 
None 
 
Summary of Treatment Arms: 
• 2A: Evaluates the mRNA1273 EUA vaccination series, plus a variant vaccine as a third dose. 
• 2B: Evaluates a 50-mcg vaccination series, plus a variant vaccine as a third dose. 
• 2C-2D: Evaluate 2 doses of the homologous variant vaccine at different dose levels. 
• 2E-2F: Evaluate heterologous prime-boost strategies at 2 dose levels. 
• 2G-2H: Evaluate a 1:1 mix of vaccine (2 doses), with the total dose for both vaccines equal to 100 mcg and 50 mcg, 
respectively. 
 

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For both Cohorts 1 and 2, reactogenicity will be assessed at the above-mentioned visits and 
blood will be drawn for immunogenicity assays. 
After the IND is in effect, IRB review and approval, and site activation, the participating sites 
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. 
4.2 
Scientific Rationale for Study Design 
This phase 1 clinical trial is designed as an open-label study, without administration of a placebo 
formulation. An open-label study will facilitate the need for rapid review and dissemination of 
study data for public health reasons. 
4.3 
Justification for Doses 
In the Phase 1 clinical trial, DMID 20-0003, mRNA-1273, administered as two injections 28 
days apart, was investigated at dosages of 25, 50, 100 and 250 mcg in subjects 18 through 55 
years of age, and at dosages of 25, 50, and 100 mcg in older cohorts (56-70 years of age and >71 
years of age) (Jackson LA et al, 2020; Anderson EJ et al, 2020). The 100-mcg dose induced 
higher antibody titers than the 25-mcg dose, whereas the 250-mcg dose did not lead to significant 
increases, which supported evaluation of the 100-mcg dose in Phase 2 and Phase 3 trials. 
Subsequent to the start of the Phase 3 trial, an interim analysis of immunogenicity data from the 
Phase 2 demonstrated that the 50 and 100-mcg doses in a two-dose series are similarly 
immunogenic (Chu L et al, 2021) and warrants further evaluation. The primary efficacy analysis 
from the Phase 3 trial evaluating a two-dose schedule of a 100-mcg mRNA-1273 vaccine led to 
the issuance of the EUA and initiation of a vaccination campaign in the United States. 
The Phase 2 trial of mRNA-1273 evaluated doses of 50 mcg and 100 mcg, administered as a 
two-vaccination series, in 600 adults ≥18 years of age. The safety profile of both formulations 
was acceptable (Chu L et al, 2021). Anti-SARS-CoV-2 S binding and neutralizing antibodies 
were induced by both dose levels of mRNA-1273 within 28 days after the first vaccination, and 
rose substantially to peak titers by 14 days after the second vaccination, exceeding levels of 
convalescent sera from COVID-19 patients. The antibodies remained elevated through the last 
timepoint assessed at 57 days. Neutralizing responses met criteria for seroconversion within 28 
days after the first vaccination in the majority of participants, with rates of 100% observed at 14 
and 28 days after the second vaccination. Binding and neutralizing antibody responses were 
generally comparable in participants who received the 100 mcg mRNA-1273 and the 50 mcg 
dose at all time points and across the age groups of ≥18 to <55 years and ≥55 years. These 
findings support the evaluation of mRNA-1273 and mRNA-1273.351 at total dosages of 50 or 
100 mcg per vaccination. 
Table 1. Cohort 1 Treatment Arms 
Arm 
Sample Size 
Vaccination 
Product and Dose 

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1A 
~30 
50 mcg mRNA-1273.351 
1B 
~30 
25 mcg mRNA-1273 
+ 25 mcg mRNA-1273.351 
Cohort 2 will include approximately 150 participants 18 through 55 years of age who have not 
received a COVID-19 vaccine, have no known history of COVID-19 or SARS-CoV-2 infection, 
and do not have underlying conditions that are associated with an increased risk of severe illness 
from SARS-CoV-2 infection. Enrollment may close before the full 150 participants based on 
estimates on the timing of immunogenicity results and the need to inform public health 
decisions. They will be randomly assigned to one of 8 treatment arms and will receive 2 or 3 IM 
injections of the vaccine (as outlined in Table 2), and followed through 12 months after the last 
vaccination. Follow-up visits will occur 7, 14, and 28 days after each vaccination, as well as 3, 6 
and 12 months post the last vaccination. 

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5. 
TABLE 3TABLE 3STUDY POPULATION 
Two cohorts will be enrolled. For Cohort 1, approximately 60 males and non-pregnant female 
subjects 18 years of age and older, who are in good health and received two vaccinations of 
mRNA-1273 at dosages of 50 mcg, 100 mcg or 250 mcg in DMID 20-0003 will be invited to 
participate in this study. 
For Cohort 2, approximately 150 males and non-pregnant females, 18 through 55 years of age, 
who have never been vaccinated against SARS-CoV-2 or are not known to have been infected 
with SARS-CoV-2, and are at low risk for severe disease, 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 4 weeks (though could take up to 8 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 vaccination. 
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 principal 
investigator (PI) or appropriate sub-investigator. No exemptions are granted on Subject Inclusion 
or Exclusion Criteria in DMID-sponsored studies. 
5.1 
Inclusion Criteria 
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. Cohort 1: previously received 2 doses of mRNA-1273 IM as part of DMID 20-0003. 
5. Cohort 1: Male or non-pregnant female, ≥18 years of age at time of enrollment. 
Cohort 2: Male or non-pregnant female, 18 through 55 years of age at time of enrollment. 
6. Women of childbearing potential1 must agree to practice abstinence or use at least one 
acceptable primary form of contraception.2,3 
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). 
2Acceptable forms of primary contraception include monogamous relationship with a 
vasectomized partner who has been vasectomized for 180 days or more prior to the 

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subject’s first vaccination, intrauterine devices, birth control pills, and 
injectable/implantable/insertable hormonal birth control products. 
3Must 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. In good health.4 
4As 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 
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 or for dose optimization, 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. 
8. Oral temperature is less than 100.0°F (37.8°C). 
9. Must agree to have samples stored for secondary research. 
10. Agrees to adhere to Lifestyle Considerations (defined in Section 5.4) throughout study 
duration. 
11. Must agree to refrain from donating blood or plasma during the study (outside of this 
study). 
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 prior to each vaccine administration. 
2. BMI >40.0 kg/m2. 
3. Female subject who is breastfeeding. 
4. Has any medical disease or condition that, in the opinion of the participating site PI or 
appropriate sub-investigator, precludes study participation.5 

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5Including 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. 
5. Presence of self-reported or medically documented significant medical or psychiatric 
condition(s).6 
6Significant 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. 
Type 2 diabetes mellitus, not including prediabetes. 
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 each 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 protocol. 
7. Has participated in another investigational study involving any investigational product8 
within 5 half-lives before the first vaccine administration. 
8study drug, biologic or device 
8. Currently enrolled in or plans to participate in another clinical trial with an 
investigational agent9 that will be received during the study-reporting period.10 

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9Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or 
medication. 
10Up to 15 months after the first vaccination. 
9. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, 
generalized urticaria, angioedema, other significant reaction) to drugs or any previous 
licensed or unlicensed vaccines or to polyethylene glycol (PEG) or a PEG-containing 
product. 
10. Chronic use (more than 14 continuous days) of any medications that may be associated 
with impaired immune responsiveness.11 
11Including, 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. 
11. Anticipating the need for immunosuppressive treatment within the next 6 months. 
12. 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. 
13. Has any blood dyscrasias or significant disorder of coagulation. 
14. Received or plans to receive a licensed, live vaccine within 4 weeks before or after each 
vaccination. 
15. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or 
after each vaccination. 
16. Receipt of any other SARS-CoV-2 vaccine or any experimental coronavirus vaccine at 
any time prior to or during the study, except Cohort 1 subjects who received mRNA-1273 
in DMID 20-0003. 
17. Close contact of anyone known to have SARS-CoV-2 infection within 14 days prior to 
vaccine administration. 
18. History of COVID-19 diagnosis, positive SARS-CoV-2 PCR test, or, for Cohort 2 only, a 
known positive SARS-CoV-2 serologic test. 
19. On current treatment with investigational agents for prophylaxis of COVID-19. 
 
Exclusion of Specific Populations 
The effects on the fetus are not known; therefore, pregnant women will not be eligible for the 
trial. Children will not be included in this trial as presently there are no safety or efficacy data in 
adults for the variant strain. Should the outcome of this trial be deemed acceptable, additional 
trials may be initiated, including these populations. 
5.3 
Inclusion of Vulnerable Subjects 
Not Applicable 

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5.4 
Lifestyle Considerations 
During this study subjects are asked to: 
• 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. 
5.6 
Strategies for Recruitment and Retention 
 
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. 
 
Retention 
Study retention strategies will include education and explanation of the study schedule and 
procedures during screening and enrollment/baseline 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. 
 
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. 
 
Costs 

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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 
 
Study Product Description 
Product: There are two clinical presentations of mRNA-1273 — mRNA-1273 and mRNA-
1273.351 
mRNA-1273 (0.2 mg/mL) is an LNP dispersion containing an mRNA that encodes for the pre 
fusion stabilized S protein of the Wuhan-Hu-1 strain of 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-1273.351 (0.5 mg/mL) is formulated in the same way but contains mRNA that encodes 
for the prefusion stabilized S protein of the B.1.351 variant SARS-CoV-2 strain. 
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. 
 
Dosing and Administration 
mRNA-1273 (0.2 mg/mL) will be diluted in 0.9% NaCl for injection, USP to obtain the specified 
antigen content in 0.5 mL doses. 
mRNA-1273.351 (0.5 mg/mL) will be diluted in 0.9% NaCl for injection, USP to obtain the 
specified antigen content in 0.5 mL doses. 
Each dose will be administered via IM injection into the deltoid muscle. 
For Cohort 2, Arms 2A-H, the second dose of vaccine will be administered preferably in the 
same arm used for the first dose. 
For Cohort 2, Arms 2A and 2B, the third dose of vaccine will also be administered preferably in 
the same arm used for the first dose. 
The pharmacist will prepare a single dose for each subject based on cohort assignment. 
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. 

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Visually inspect the mRNA-1273 and mRNA-1273.351 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 study product 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 from the same 
final mixed vial within 30 minutes of completion of dosing solution preparation. 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 study vaccine is 8 hours at 
room temperature after the solution is drawn into the dosing syringe. 
 
4.1Dose Modifications 
No dose modifications. 
6.2 
Accountability/Handling/Storage/Preparation 
 
Acquisition and Accountability 
Product: mRNA-1273 and mRNA-1273.351 
Will be provided by ModernaTX, Inc. via the DMID CMS. 
Upon request by DMID, study product 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 

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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 study product, 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 
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 or mRNA-1273.351 vials 
• used mixing vials 
• mRNA-1273 or mRNA-1273.351 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 study product vials, used 0.9% NaCl Injection vials and used mixing vials. 
Destruction 

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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 study product 
vials should occur as noted: 
• Unused and used study product 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. 
 
Formulation and Appearance 
Product: mRNA-1273 and mRNA-1273.351 
mRNA-1273 is provided as a sterile liquid for injection, white to off-white dispersion in 
appearance. 
mRNA-1273.351 is provided as a sterile liquid for injection, white to off-white dispersion in 
appearance. 
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.” 
Sterile empty vials (2-mL or 10-mL) will be provided with latex-free stoppers. 
 
Product Storage and Stability 
Product: mRNA-1273 and mRNA-1273.351 
mRNA-1273 vials are stored frozen between -25º to -15ºC. Vials can be stored refrigerated 
between 2° to 8°C for up to 30 days prior to first use. Unpunctured vials may be stored between 
8° to 25°C for up to 12 hours. Do not refreeze. Store in the original carton to protect from light. 
mRNA-1273.351 vials are stored frozen between -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. Store in 
the original carton to protect from light. 
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.] 

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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 and mRNA-1273.351 must be stored in a secure area with limited access 
(pharmacy staff only), and must be stored frozen. 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 
and mRNA-1273.351 that was not temperature controlled during shipment or during storage to 
the pharmacy staff. Such mRNA-1273 and mRNA-1273.351 will be retained for inspection by 
the pharmacy staff and disposed of according to approved methods. 
 
Preparation 
Refer to the protocol-specific MOP for details about preparation. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
 
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. 
 
Randomization and Blinding 

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Subjects in Cohort 1 will be stratified by DMID 20-0003 cohort (age and dosage group) and 
randomized 1:1 to Arm 1A or 1B. Subjects in Cohort 2 will be randomized in a ratio of 
3:3:4:4:4:4:4:4 for Arms 2A-H. Randomization will be done in the SDCC’s Advantage 
eClinicalSM (Electronic Data Capture System). 
 
Blinding and Masking Procedures 
This study is unblinded. 
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 
Concomitant medications include only prescription medications and vaccines received outside of 
the study taken by the subject at the time of enrollment through 28 days after the last vaccination. 
At each study visit, if there are new SAEs, Protocol Specified AESIs, MAAEs, or NOCMCs, 
concomitant medications should be recorded on the appropriate DCF. 
 
Rescue Medicine 
Not Applicable 
 
Non-Research Standard of Care 
Not Applicable 
7. 
STUDY INTERVENTION DISCONTINUATION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Pausing Criteria and Discontinuation of Study Intervention 
 
Pausing 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. 
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. 

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5- Three (3) or more subjects experience a Grade 3 AE (unsolicited) related to vaccine 
administration, in the same Preferred Terms based on the Medical Dictionary for 
Regulatory Activities (MedDRA) coding. 
 
Criteria for Continuation of Dosing and Redosing 
In the event a pausing rule is met: 
• an unscheduled safety analysis by the SMC will be required for approval of further 
enrollment, and 
• further administration of any study vaccine, including a second or third dose, is 
suspended for ALL subjects until an assessment by the SMC takes place. 
 
Discontinuation of Study Intervention 
For Cohort 2, Arms 2A-H, prior to receiving the second vaccination, and, for Arms 2A and 2B, 
prior to receiving the third vaccination, subjects will be reassessed. The following events 
constitute contraindications to any further administration of study vaccines. If any of these events 
occur during the study prior to the second vaccination, the subject must not receive the second 
vaccination but will be encouraged to continue study participation for safety and immunogenicity 
evaluations through 12 months after their last vaccination. For Cohort 2, Arms 2A and 2B, if any 
of these events occur after the second vaccination and before the third vaccination the subject 
must not receive the third vaccination but will be encouraged to continue study participation for 
safety and immunogenicity evaluations through 12 months after their last vaccination. 
• 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. 
• Confirmed SARS-CoV-2 infection. 
• Anaphylaxis or unexpected systemic hypersensitivity reaction following the 
administration of a prior study vaccination. 
• Any SAE judged to be related to vaccine. 
• Pregnancy. 
• New information becomes available that makes further participation unsafe or interferes 
with the evaluation of responses. 
• 
Termination of this trial. 
7.1.3.1 
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. 
• 
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. 

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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. 
It is preferred that the vaccination still occur within the window specified in the SOA if possible 
but delays outside the windows are permitted (would still be a protocol deviation). 
 
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. 
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. 
• Initial 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 or third 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 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, interferes with the subject’s successful 
completion of this study, or interferes with the evaluation of responses. 
• If any AE or situation occurs such that continued participation in the study would not be 
in the best interest of the subject. 
• Any SAE judged to be related to vaccine. 

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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. 
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 
 
Screening or Enrollment/Baseline 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 the enrollment/baseline visit. Screening assessments can 
occur up to 42 days before or at the subject’s first vaccination visit (Day 1). At the screening 
(optional) or enrollment/baseline 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 (optional) or 
enrollment/baseline visit to determine eligibility requirements as specified in the inclusion and 
exclusion criteria: 
• 
Obtain medical history. 
• 
Review pre-study medications and therapies at screening and record on the appropriate 
DCF. Review of adult vaccinations, including any other SARS-CoV-2 or other 
experimental coronavirus vaccines. 
• 
Review any participation in investigational trials in the last 6 months. 
• 
Measure vital signs (HR, BP, and oral temperature), and height and weight for 
determination of BMI. 
• 
Review of birth control history with female subjects. 
• 
Counsel subjects to use adequate birth control methods required during the trial to avoid 
pregnancy. 
• Urine pregnancy test (in women of childbearing potential). 

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• 
Review inclusion and exclusion criteria. 
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 unless the screening and vaccination are scheduled 
on the same day. 
If a physiologic parameter, e.g., vital signs, 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. 
Subjects will be provided the results of 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. 
The screening and first vaccination procedures can be both conducted at the enrollment/baseline 
visit. 
 
Immunogenicity Evaluations 
Serological Immunogenicity Assays: 
The following serological immunogenicity assays will be performed: 
• IgG ELISA to SARS-CoV-2 proteins. 
• Neutralization assays using a SARS-CoV-2 pseudovirus. 
• Neutralization assay using live SARS-CoV-2. 
Preparation of blood samples and shipping instructions for serological immunogenicity assays 
are outlined in the protocol-specific MOP. Inability (e.g., failure of venipuncture) 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 B and T cell immune responses using multiparametric flow 
cytometry. 
Refer to the protocol-specific immune monitoring plan for details. 

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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 
TablesTable 9,Table 10 andTable 11. 
 
Samples for Genetic/Genomic Analysis 
8.1.3.1 
Genetic/Genomic Analysis 
DNA obtained from B-cells may be sequenced to identify 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. 
8.1.3.2 
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 
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. 
8.1.3.3 
Management of Results 
All genetic testing in this protocol will be performed for research purposes 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 (optional) or enrollment/baseline visit. Subjects will be queried 
regarding a history of significant medical disorders. 
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 to identify 
intercurrent Protocol Specified AESIs, MAAEs, and NOCMCs. 
• Physical examination: 
o A symptom-directed (targeted) physical examination will be performed if 
indicated at any timepoint at the discretion of the participating site PI or 
appropriate sub-investigator, if necessary, to evaluate AEs. 

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o Reactogenicity assessments of solicited AEs occurring from the time of 
vaccination through 7 days post 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 30 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 7 days after vaccination. 
• 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 
vaccination days, 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. 
o Urine pregnancy test: Urine pregnancy test will be performed locally by the site 
laboratory within 24 hours prior to each vaccination, 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 as applicable. 
• Memory aid: 
o All subjects will complete a Memory Aid from the time of each vaccination 
through 7 days post each 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 7 
days after each vaccination. Based on the information collected, subjects may be 
asked to return to the clinic for evaluation. Memory Aids will be collected and 
subjects will be assessed for delayed onset local reactions 14 days after each 
vaccination. 
 

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Table 9: Venipuncture Volumes for Cohort 1 (One Vaccination) 
Study Day 
-42 to -1 
1 
8 
15 
29 
91 
181 
366 
Early 
Termination 
Visit 
Total 
Volume 
of Blood 
Drawn 
(mL) 
Visit Window (±number of days) 
 
0 
1 
2 
2 
7 
7 
14 
 
 
Study Visit 
Screening 
(optional) 
00 
01 
02 
03 
04 
05 
06 
07 
 
 
Vaccination  
  
X  
 
 
 
 
 
 
 
 
Serum for Serological Immunogenicity 
Assays1 
 
16 
  
16  
16  
16  
16  
16  
162 
96  
PBMCs (and Plasma) for Cellular 
Immunology Assays 
  
64 
 
64  
  
  
64  
64 
162or 402 
256 
Serum for Secondary Research 
  
16 
 
16  
16  
16  
16  
16  
162 
96  
Per Visit Blood Volume Total (mL)  
  
96 
 
96 
32  
32  
96  
96 
  
448 
Cumulative Blood Volume (mL) (prior 56 
days)  
  
112*  
112  
208  
240 
32 
96 
96 
  
  
Running Blood Volume Total (mL)  
  
96 
96 
192  
224  
256 
352 
448 
  
  
1 Inability (e.g., failure of venipuncture) 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 blood volume is collected. 
2 These blood volumes are not included in the blood volume totals. Blood volume depends upon day of early 
termination visit. 
*16 mL was drawn concurrently as part of the early termination visit from DMID 20-0003. 
 
 

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Table 10: Venipuncture Volumes for Cohort 2: 2A-B (Three Vaccinations) 
Study Day 
-42 to -1 
1 
8 
15 
29 
36 
43 
57 
64 
71 
85 
147 
237 
422 
Early 
Term 
Visit 
Total 
Volume 
of 
Blood 
Drawn 
(mL) 
Visit Window (±number 
of days) 
 
0 
1 
2 
2 
1 
2 
2 
1 
2 
2 
7 
7 
14 
 
 
Study Visit 
Screening 
(optional) 
00 
01 
02 
03 
04 
053 
063 
073 
084 
094 
104 
114 
124 
134 
 
 
Vaccination  
  
X  
  
  
X  
  
  
X  
 
 
 
 
 
 
 
 
Serum for Serological 
Immunogenicity Assays1 
  
16 
  
16  
16  
  
16  
16  
  
16  
16  
16  
16  
16  
162 
160  
PBMCs (and Plasma) for 
Cellular Immunology 
Assays  
  
64 
  
48 
40  
  
64 
40  
  
64 
 
  
64 
64  
162or 
402 
448  
Serum for Secondary 
Research  
  
16 
  
16  
16  
  
16  
16  
  
16  
16  
16  
16  
16  
162 
160 
Per Visit Blood Volume 
Total (mL)  
  
96 
  
80  
72  
  
96 
72  
  
96  
32  
32  
96  
96  
  
768  
Cumulative Blood 
Volume (mL) (prior 56 
days)  
  
96 
96  
176  
248  
248  
344  
416  
320  
416  
368  
64  
96  
96  
  
  
Running Blood Volume 
Total (mL)  
  
96 
96  
176  
248  
248  
344  
416  
416 
512  
544 
576  
672  
768  
  
  
1 Inability (e.g., failure of venipuncture) 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 blood volume is collected. 
2 These blood volumes are not included in the blood volume totals. Blood volume depends upon day of early termination visit. 
3 Visits 05-07 windows should be based off the actual Visit 04 date. 
4 Visits 08-13 windows should be based off the actual Visit 07 date. 
 
 

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Table 11: Venipuncture Volumes for Cohort 2: 2C-H (Two Vaccinations) 
Study Day 
-42 to -1 
1 
8 
15 
29 
36 
43 
57 
119 
209 
394 
Early 
Term 
Visit 
Total 
Volume 
of 
Blood 
Drawn 
(mL) 
Visit Window (±number 
of days) 
 
0 
1 
2 
2 
1 
2 
2 
7 
7 
14 
 
 
Study Visit 
Screening 
(optional) 
00 
01 
02 
03 
04 
053 
063 
073 
083 
093 
103 
 
 
Vaccination  
  
X  
  
  
X  
 
 
 
 
 
 
 
 
Serum for Serological 
Immunogenicity Assays1 
  
16  
  
16  
16  
  
16  
16  
16  
16  
16  
162 
128 
PBMCs (and Plasma) for 
Cellular Immunology 
Assays  
  
64 
  
48  
40  
  
64  
 
 
64  
64  
162or 
402 
 344 
Serum for Secondary 
Research  
  
16  
  
16  
16  
 
16  
16  
16  
16  
16  
162 
128  
Per Visit Blood Volume 
Total (mL)  
  
96  
  
80  
72  
 
96  
32  
32  
96  
96  
  
600  
Cumulative Blood 
Volume (mL) (prior 56 
days)  
  
96  
96 
176  
248 
248  
344  
376  
64  
96 
96  
  
  
Running Blood Volume 
Total (mL)  
  
96 
96 
176 
248 
248 
344 
376 
408 
504 
600 
  
  
1 Inability (e.g., failure of venipuncture) 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 blood volume is 
collected. 
2 These blood volumes are not included in the blood volume totals. Blood volume depends upon day of 
early termination visit. 
3 Visits 05-10 windows should be based off the actual Visit 04 date. 
 

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Procedures to be Followed in the Event of Abnormal Clinical Findings 
If a physiologic parameter, e.g., vital signs, 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 that occur post vaccination will be considered AEs. 
8.3 
Adverse Events and Serious Adverse Events 
 
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, 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 last vaccination. After 28 days post last 
vaccination through the end of study, 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. 
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. 

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For this study, solicited AEs will be: 
• 
Injection site Pain 
• 
Injection site Erythema 
• 
Injection site Edema/Induration 
• 
Headache 
• 
Fatigue 
• 
Myalgia 
• 
Arthralgia 
• 
Nausea 
• 
Fever 
• 
Chills 
Subjects will also be assessed for delayed onset local reactions through 14 days post each 
vaccination. 
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 28 days post last vaccination. 
After 28 days post last vaccination through the end of study, only SAEs, Protocol Specified 
AESIs, MAAEs, and NOCMCs (as detailed in Section 8.3.2) will be reported as AEs. 
8.3.1.3 
Special Reporting of Adverse Events 
Not Applicable 
 
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. 

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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. 
 
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. 
 
Classification of an Adverse Event 
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 and 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. 

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• 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. 
 
Time Period and Frequency for Event Assessment and Follow-Up 
For this study: 
• solicited AEs will be collected for 7 days post each vaccination. 
• unsolicited AEs will be collected until 28 days post last vaccination 
• SAEs, Protocol Specified AESIs, MAAEs, and NOCMCs will be collected from Day 1 
through the end of the study. 
 
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. 
 
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: 

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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 
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. 
 
Reporting Events to Subjects 
Subjects will be informed of any AEs or SAEs that occur as part of their participation in this 
trial. 
 
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. An adverse event of special interest (serious or 
nonserious) is one of scientific and medical concern specific to the sponsor’s product or 

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program, for which ongoing monitoring and rapid communication by the investigator to the 
sponsor is required. Such an event may require further investigation in order to characterize and 
understand it. Depending on the nature of the event, rapid communication by the trial sponsor to 
other parties (e.g., regulators) may also be required. 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: See Section 12, Appendix A. 
o All suspected cases of anaphylaxis should be recorded. For reporting purposes, a 
participant who displays signs/symptoms consistent with anaphylaxis should be 
reported as a potential case of anaphylaxis. 
o All suspected cases of myocarditis or pericarditis should be recorded. For 
reporting purposes, a participant 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 a hospitalization, emergency room visit or an otherwise 
unscheduled visit to or from medical personnel for any reason; and considered related to 
study product. 
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 
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. 
 
Reporting of Pregnancy 
Pregnancy is not an AE. However, any pregnancy that occurs during study participation (through 
the end of the study) should be reported to the sponsor on the appropriate DCF. Pregnancy 
should be followed to outcome. 

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8.4 
Unanticipated Problems 
 
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. 
 
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. 
 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 Day 1 through 28 days after last 
vaccination. 
 
Reporting Unanticipated Problems to Subjects 
Subjects will be informed of any UPs that occur as part of their participation in this trial. 
9. 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
This is a phase 1, open-label, randomized 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-1273.351 alone and in combination with mRNA-
1273. 
9.2 
Sample Size Determination 

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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 12. 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 approximately 
30 subjects in each arm (Arms 1A and 1B), the chance of observing at least one AE of 
probability 10% or more is approximately 96%. Therefore, if no AEs of a given type occur in a 
Cohort 1 Arm, we can be relatively confident that they will occur in fewer than 10% of people 
once the vaccine is implemented. With approximately 60 subjects across these two Arms (1A 
and 1B), 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 Cohort 1, we can be very confident that any 
combination independent event will occur in fewer than 5% of people once the vaccine is 
implemented as a boost. 
With 15 subjects in Arms 2A and 2B, 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 Arms 2A or 2B, we 
can be relatively confident that they will occur in fewer than 20% of people once the vaccine is 
implemented. With 20 subjects in each arm (Arms 2C-2H), the chance of observing at least one 
AE of probability 20% or more is approximately 99%. Therefore, if no AEs of a given type 
occur in Arms 2C-2H, we can be relatively confident that they will occur in fewer than 20% of 
people once the vaccine is implemented. With approximately 150 subjects across these eight 
Arms (2A-2H), the chance of observing at least one AE of probability 3% or more is at least 
99%. Therefore, if no AEs of a given type occur across Cohort 2, we can be very confident that 
any dosage/combination independent event will occur in fewer than 3% of people once the 
vaccine is implemented. 
 

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Table 12: Probability of Observing an Adverse Event for Various Event Rates 
Cohort 1 
N 
“True” 
Event 
Rate 
Probability of 
Observation (%) 
N 
“True” 
Event 
Rate 
Probability of 
Observation (%) 
30 
0.1% 
3.0 
60 
0.1% 
5.8 
0.5% 
14.0 
0.5% 
26.0 
1.0% 
26.0 
1.0% 
45.3 
2.0% 
45.5 
2.0% 
70.2 
3.0% 
59.9 
3.0% 
83.9 
4.0% 
70.6 
4.0% 
91.4 
5.0% 
78.5 
5.0% 
95.4 
10.0% 
95.8 
10.0% 
99.8 
15.0% 
99.2 
15.0% 
>99.9 
20.0% 
99.9 
20.0% 
>99.9 
Cohort 2 
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 
20 
0.1% 
2.0 
150 
0.1% 
13.9 
0.5% 
7.2 
0.5% 
9.5 
0.5% 
52.9 
1.0% 
14.0 
1.0% 
18.2 
1.0% 
77.9 
2.0% 
26.1 
2.0% 
33.2 
2.0% 
95.2 
3.0% 
36.7 
3.0% 
45.6 
3.0% 
99.0 
4.0% 
45.8 
4.0% 
55.8 
4.0% 
99.8 
5.0% 
53.7 
5.0% 
64.2 
5.0% 
>99.9 
10.0% 
79.4 
10.0% 
87.8 
10.0% 
>99.9 
15.0% 
91.3 
15.0% 
96.1 
15.0% 
>99.9 
20.0% 
96.5 
20.0% 
98.8 
20.0% 
>99.9 
 

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9.3 
Populations for Analyses 
The Safety Analysis population for the study includes all subjects who received one dose of 
study vaccine. Analyses for the safety population will include safety reported through the end of 
the study. The modified intent-to-treat (mITT) population includes all subjects who received at 
least one dose of vaccine and contributed both pre- and at least one post-vaccination venous 
blood sample 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 to the protocol deviations that are considered to affect the 
science. 
• 
Data from any visit that occurs substantially out of window. 
9.4 
Statistical Analyses 
Interim analyses of safety, reactogenicity, and immunologic response data will be done, as 
needed. 
The final analysis will be performed after the final data lock 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. 
 
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. 
 
Analysis of the Primary Endpoint(s) 
Section 9.4.4 describes the analyses of Safety which is the primary endpoint of this protocol. 
 
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. 

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Seroconversion rates, GMFR and GMT for SARS-CoV-2 as measured by a range of assays 
measuring total Spike-specific IgG (ELISA-based) and function (neutralization, receptor binding 
domain (RBD) binding, or similar) will be calculated for all timepoints by arm 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. 
 
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 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 first vaccination through 28 days 
after the last 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. The numbers of SAEs, 
Protocol Specified AESIs 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. 
 
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 arm 
and cohort. 
 
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 study is ongoing. Any ad-hoc analyses, jointly developed by the SDCC 
and/or the Vaccine Research Center (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. 

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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 may be 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 Cohort 1 have been dosed and 
completed Day 8. The SMC will also review cumulative AE data after all subjects in Cohort 2 
have been dosed and prior to the second vaccination (preferably after all subjects have completed 
Day 8). Reports may be combined if projected milestones for reports will occur close enough to 
each other where, in the opinion of the protocol team, producing one report, as opposed to two 
separate reports, is more informative regarding the safety of subjects and more beneficial to the 
overall needs of the protocol team. 
9.4.6.2 
Interim Immunogenicity Review 
Interim data review of immunogenicity may be performed to inform public health decisions. 
Statistical analyses of secondary immunogenicity endpoints, by vaccine schedule group, may be 
performed when subjects have completed key immunogenicity visits. Immunogenicity reviews 
may be shared with the SMC, as determined by DMID. 
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. 
 
Sub-Group Analyses 
The protocol does not define any formal subgroup analyses, and the study is not adequately 
powered to perform subgroup analyses. 
 
Tabulation of Individual Subject Data 
In general, all data will be listed, sorted by arm and subject, and when appropriate by visit 
number within subject. 
 
Exploratory Analyses 
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 innate immune cells and SARS-CoV-2 specific B 
cells will be summarized at each timepoint by arm. 
The magnitude, phenotype and percentage of cytokine producing S protein-specific T cells will 
be summarized at each timepoint by arm. 
 
 

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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. 
 
Informed Consent Process 
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. 

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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. 
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. 

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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 on primary and secondary 
research samples, including but not limited to transcriptomics and 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. 
If subjects choose not to provide permission for extra blood and secondary research use, they 
will not be eligible for enrollment into the study. 
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. 
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. 
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 SARS-CoV-2 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. 

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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. 
 
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: 
• 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. 
 
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) 

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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. 
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. 
 
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. 

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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 
Research Consortium (IDCRC) sites or other institutions, or company-designated research 
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. 

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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. 
 
Safety Oversight 
10.1.6.1 
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 Cohort 1 have been dosed and 
completed Day 8. The SMC will also review cumulative AE data after all subjects in Cohort 2 
have been dosed and prior to the second vaccination (preferably after all subjects have completed 
Day 8). 
Ad hoc reviews will occur when trial halting criteria are met, or as requested by the sponsor or 
PI. 
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. 
 
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/ 
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 

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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. 
 
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. 
 
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. 
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. 

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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. 
 
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 
records. 
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 

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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. 
 
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. 
 
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. 
 
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. 
 
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. 
 
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 
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. 

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10.2 
Additional Considerations 
 
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 vaccines, mRNA-1273 and mRNA-1273.351, manufactured by 
ModernaTX, Inc. are covered under the PREP Act, as described in Section 2.1.1. 
10.3 
Abbreviations 
Table 13: Abbreviations 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
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 
COC 
Certificate of Confidentiality 
COPD 
Chronic Obstructive Pulmonary Disease 
CoV 
Coronavirus 
COVID-19 
Coronavirus Disease 2019 
CRF 
Case Report Form 
CROMS 
Clinical Research Operations and Management Support 
CSR 
Clinical Study Report 
CQMP 
Clinical Quality Management Plan 
DCF 
Data Collection Form 

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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 
HEENT 
Head, Ears, Eyes, Nose, and Throat 
HLA 
Human Leukocyte Antigen 
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 
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 

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mL 
Milliliter 
mm Hg 
Millimeter of Mercury 
MOP 
Manual of Procedures 
mRNA 
Messenger Ribonucleic Acid 
N 
Number (typically refers to subjects) 
NaCl 
Sodium Chloride 
NDA 
New Drug Application 
Neut 
Neutralizing 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
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 
PP 
Per Protocol 
PREP Act 
Public Readiness and Emergency Preparedness Act 
QA 
Quality Assurance 
QC 
Quality Control 
RDB 
Receptor Binding Domain 
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 
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 
 

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10.4 
Protocol Amendment History 
Table 14: Protocol Amendment History 
Version, Date 
Section 
Description of Change  
Brief Rationale 
2.0,  
March 22, 
2021 
Throughout Administrative. 
Advanced version and date. 
Throughout Added two treatment arms to 
Cohort 2, adjusted the sample 
size of each Cohort 2 treatment 
arm, revised the summary of 
Cohort 2 treatment arms, and 
updated Cohort 1 and 2 
probability table. 
To address IND non-hold 
and SMC comments. 
Throughout Added Protocol Specified 
AESIs, including Section 12, 
Appendix A: AESIs Terms 
To address Manufacturer 
surveillance request. 
Throughout Added assess for delayed onset 
local reactions through 14 days 
post each vaccination. 
To address SMC comments. 
1.2 
Updated SOA for Cohort 1 
(One Vaccination) table as 
follows: 
• Study Day 85 to 91. 
• Study Day 169 to 181. 
To address PI comment. 
2.2.1 
Added dermal filler risk. 
To address SMC comments. 
2.2.1 
Added “There is limited 
experience with administration 
of a third dose of the mRNA 
COVID-19 vaccines, and it is 
possible that the third dose may 
be associated with more 
frequent or more severe adverse 
events.” 
To address PI comment. 
7.1.3 
Added confirmed SARS-CoV-2 
infection and interferes with the 
evaluaton of responses. 
To address SMC comments. 
8.2 
Updated Venipuncture Volumes 
for Cohort 1 (One Vaccination) 
table as follows: 
• Study Day 85 to 91. 
• Study Day 169 to 181. 
• Cumulative Blood 
Volume (mL) (prior 56 
days) for Study Days 29 
(280 to 240), 91 (64 to 
To address PI comment. 

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Version, Date 
Section 
Description of Change  
Brief Rationale 
32), 181 (80 to 96), and 
366 (80 to 96). 
8.3.9 
Expanded AESI definition and 
added AESI reporting of 
suspected cases of anaphylaxis. 
To address Manufacturer 
surveillance request. 
3.0,  
July 30, 2021 
Throughout Administrative. 
Advanced version and date. 
Protocol 
Summary, 
Study 
Design and 
Sect. 4.1 
Added: Enrollment may close 
before the full 150 participants 
based on estimates on the 
timing of immunogenicity 
results and the need to inform 
public health decisions. 
Updated enrollment plan. 
Sect. 2.2.1 
Myocarditis and pericarditis 
added to the risks of mRNA-
1273 and mRNA-1273.351. 
Per updated Moderna 
COVID-19 EUA Vaccine 
Fact Sheet. 
Sect. 8.3.9 
Myocarditis and pericarditis 
classified as protocol specified 
AESIs. 
To address Manufacturer 
surveillance request. 
 
11. 
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5. Chu L., McPhee R., Huang W., Bennett H., Pajon R., Nestorova B., Leav B., … mRNA-
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vaccine-offers-solid-protection-against-severe-disease. Accessed 02 Feb 2021.  
 
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mutants from global SARS-CoV-2 variants. bioRxiv : the preprint server for biology, 
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21-25. 
 
 
 

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12. 
APPENDIX A: ADVERSE EVENTS OF SPECIAL INTEREST 
(AESIS) TERMS 
 
Investigators should report all events which fall into the following categories as an AESI per the 
reporting processes specified in the protocol. The following AESIs are medical concepts that 
may be related to COVID-19 or are of interest in COVID-19 vaccine safety surveillance. Even if 
the events below occur in the setting of a COVID infection, the event should still be reported as 
an AESI if it is one of the medical concepts below. 
 
Medical Concept 
Additional Notes 
Anosmia, Ageusia 
• New onset COVID associated or idiopathic events 
without other etiology excluding congenital etiologies or 
trauma 
Subacute thyroiditis 
• Including but not limited to events of: atrophic 
thyroiditis, autoimmune thyroiditis, immune-mediated 
thyroiditis, silent thyroiditis, thyrotoxicosis and 
thyroiditis 
Acute pancreatitis 
• Including but not limited to events of: autoimmune 
pancreatitis, immune-mediated pancreatitis, ischemic 
pancreatitis, edematous pancreatitis, pancreatitis, acute 
pancreatitis, hemorrhagic pancreatitis, necrotizing 
pancreatitis, viral pancreatitis, and subacute pancreatitis 
• Excluding known etiologic causes of pancreatitis 
(alcohol, gallstones, trauma, recent invasive procedures) 
Appendicitis 
• Include any event of appendicitis  
Rhabdomyolysis 
• New onset rhabdomyolysis without known etiology 
such as excessive exercise or trauma 
Acute respiratory distress 
syndrome (ARDS) 
• Including but not limited to new events of ARDS and 
respiratory failure 
Coagulation disorders 
• Including but not limited to thromboembolic and 
bleeding disorders, disseminated intravascular 
coagulation, pulmonary embolism, deep vein thrombosis 
Acute cardiovascular injury 
• Including but not limited to myocarditis, pericarditis, 
microangiopathy, coronary artery disease, arrhythmia, 
stress cardiomyopathy, heart failure, or acute 
myocardial infarction 
Acute kidney injury 
• Include events with idiopathic or autoimmune etiologies 
• Exclude events with clear alternate etiology (trauma, 
infection, tumor, or iatrogenic causes such as 
medications or radiocontrast etc.) 
• Include all cases that meet the following criteria:  
o Increase in serum creatinine by ≥ 0.3 mg/dl 
(≥26.5 umol/l) within 48 hours; 

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Medical Concept 
Additional Notes 
o OR Increase in serum creatinine to ≥ 1.5 times 
baseline, known or presumed to have occurred 
within prior 7 days 
o OR Urine volume ≤0.5 ml/ kg/ hour for 6 hours 
Acute liver injury 
• Include events with idiopathic or autoimmune etiologies 
• Exclude events with clear alternate etiology (trauma, 
infection, tumor, etc.) 
• Include all cases that meet the following criteria 
o > 3-fold elevation above the upper normal limit 
for ALT or AST 
o OR • > 2-fold elevation above the upper normal 
limit for total serum bilirubin or GGT or ALP 
Dermatologic findings 
• Chilblain-like lesions 
• Single organ cutaneous vasculitis 
• Erythema multiforme 
• Bullous rashes 
• Severe cutaneous adverse reactions including but not 
limited to: Stevens-Johnson Syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN), Drug Reaction with 
Eosinophilia and Systemic Symptoms (DRESS) and 
fixed drug eruptions 
Multisystem inflammatory 
disorders 
• Multisystem inflammatory syndrome in adults (MIS-A) 
• Multisystem inflammatory syndrome in children (MIS-
C) 
• Kawasaki’s disease 
Thrombocytopenia 
• Platelet counts < 150 x10^9 
• Including but not limited to immune thrombocytopenia, 
platelet production decreased, thrombocytopenia, 
thrombocytopenic purpura, thrombotic 
thrombocytopenic purpura, or HELLP syndrome 
Acute aseptic arthritis 
• New onset aseptic arthritis without clear alternate 
etiology (e.g., gout, osteoarthritis, and trauma) 
New onset of or worsening of 
neurologic disease 
• Including but not limited to: 
o Guillain-Barre Syndrome 
o Acute disseminated encephalomyelitis (ADEM) 
o Peripheral facial nerve palsy (Bell’s palsy)  
o Transverse myelitis 
o Encephalitis/Encephalomyelitis 
o Aseptic meningitis 
o Febrile seizures 
o Generalized seizures/convulsions 
o Stroke (Hemorrhagic and non-hemorrhagic) 
o Narcolepsy 

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Medical Concept 
Additional Notes 
Anaphylaxis 
• Anaphylaxis is an acute hypersensitivity reaction with 
multi-organ-system involvement that can present as, or 
rapidly progress to, a severe life-threatening reaction. It 
may occur following exposure to allergens from a 
variety of sources. Anaphylaxis is a clinical syndrome 
characterized by: 
o sudden onset AND 
o rapid progression of signs and symptoms AND 
o involving two or more organ systems, as 
follows: 
o Skin/ mucosal: urticaria (hives), generalized 
erythema, angioedema, generalized pruritus with 
skin rash, generalized prickle sensation, red and 
itchy eyes 
o Cardiovascular: measured hypotension, clinical 
diagnosis of uncompensated shock, loss of 
consciousness or decreased level of 
consciousness, evidence of reduced peripheral 
circulation 
o Respiratory: bilateral wheeze (bronchospasm), 
difficulty breathing, stridor, upper airway 
swelling (lip, tongue, throat, uvula, or larynx), 
respiratory distress, persistent dry cough, hoarse 
voice, sensation of throat closure, sneezing, 
rhinorrhea 
o Gastrointestinal: diarrhea, abdominal pain, 
nausea, vomiting 
• Follow reporting procedures in protocol. 
Other syndromes 
• Fibromyalgia 
• Postural Orthostatic Tachycardia Syndrome 
• Chronic Fatigue Syndrome (Includes Myalgic 
encephalomyelitis and Post viral fatigue syndrome)